The combination of diagnostics and therapeutics is growing rapidly in cancer treatment. Here, using upconversion
nanoparticles coated with chitosan conjugated with a targeting molecule and loaded with indocyanine green (ICG), an
excitation-selectable nanoprobe with highly integrated functionalities, including the emission of visible and near-infrared
(NIR) light, strong optical absorption in the NIR region and high photostability was developed. After injected in mice, the
nanoprobes targeted to the tumor vascular system. NIR lasers (980 and 808 nm) were then selectively applied to the mice.
The results show that, the emitted upconversion fluorescence and NIR fluorescence can be used in a complementary
manner for high signal/noise ratio and sensitive tumor imaging for more precise tumor localization; Highly effective
photothermal therapy can be realized using 808 nm laser irradiation. The upconversion fluorescence at 654 nm is useful for
monitoring treatment effect during thermal therapy. In summary, using the nanoprobes, outstanding therapeutic efficacy
could be realized and the nanofabrication strategy would highlight the promise of upconversion nanoparticles in cancer
theranostics.
Reactive oxygen species (ROS) produced by photodynamic therapy (PDT) is recorded in vivo using a chemiluminescence (CL)-based gated optical system. A novel approach is developed to utilize the fluorescence (FL) of the CL probe as an internal fluorescence to calibrate the observed CL on pharmacokinetics of the probe in situ. The results show that during an in vivo PDT session, the intensity of CL decreases significantly and the decaying of CL is governed by fast and slow time components. By comparing the temporal profile of FL to that of the corresponding CL, it is found that the slow component is mainly attributed to the probe pharmacokinetics, whereas the fast component is likely due to rapid oxygen consumption as a result of PDT treatment. With carefully selected criteria, it is possible to minimize the effect of probe pharmacokinetics. This significantly improves the monitoring method for practical applications.
KEYWORDS: Photodynamic therapy, Skin, Oxygen, Luminescence, In vivo imaging, Chemiluminescence, Tissue optics, In situ metrology, Signal detection, Light scattering
Singlet oxygen (1O2) is an important factor mediating cell killing in photodynamic therapy (PDT). We previously reported that chemiluminescence (CL) can be used to detect 1O2 production in PDT and linked the signal to the PDT-induced cytotoxicity in vitro. We develop a new CL detection apparatus to achieve in vivo measurements. The system utilizes a time-delayed CL signal to overcome the interference from scattered excitation light, thus greatly improving the accuracy of the detection. The system is tested on healthy skin of BALB/ca mouse for its feasibility and reliability. The CL measurement is made during a synchronized gating period of the irradiation light. After each PDT treatment and in situ CL measurement, the skin response is scored over a period of 2 weeks. A remarkable relationship is observed between the score and the CL, regardless of the PDT treatment protocol. Although there are many issues yet to be addressed, our results clearly demonstrate the feasibility of CL measurement during PDT and its potential for in vivo PDT dosimetry. This requires further investigations.
Background: photodynamic therapy (PDT) mediated with vascular acting photosensitizer Tookad
(pd-bacteriopheophorbide) was investigated as an alternative modality for treating prostate cancer.
Our previous studies show that Tookad PDT can induce marked prostatic tissue lesion but minimal
urethral lesion. In this study a transurethral procedure was used to evaluate the response of the
prostatic urethra to direct urethral irradiation. Materials and Methods: Tookad solution (2.5
mg/ml) was administered (1 mg/kg) through IV catheter by an infusion pump over 10 min. A
diffuser fiber (1 cm active length) was inserted into the prostatic urethra. The light irradiation (50
or 100 J/cm) started at 4 min after the onset of drug infusion. Urinalysis was performed for 24 - 48
h post PDT. One week after PDT, prostates (n = 4) were removed at necropsy and subjected to
histopathological examination. Results: The cross section of prostates showed severe hemorrhagic
and necrotic lesions on the right lobe. The diameter of the lesion, measured from urethra to capsule,
was >13 mm for 50 J/cm treatment and >18 mm for 100 J/cm, respectively. Although underlying
periurethral lesion was visible, the urethral surface was intact and prostatic urethra was open.
Conclusions: The joint point of the diffuser tip and the guide fiber might be bent while passing
through the sharp turn at the Ischial Arch, which could affect the light distribution and cause the
asymmetric lesion. Nonetheless, the transurethral direct irradiation can induce marked prostatic
tissue lesion but minimal urethral lesion.
Photodynamic therapy (PDT) is an important method to treat tumor. It is known that singlet oxygen (1O2) is the main
factor mediating cytotoxicity in PDT. The effectiveness of a PDT treatment is directly linked to the 1O2 produced in the
target. So to control the dose of 1O2 is very important. Although the luminescence from 1O2 can be detected and is
suggested as an indicator for evaluating photodynamic therapy, the inherited disadvantages limit its potential for in vivo
applications. We have previously reported that chemiluminescence (CL) can be used to detect 1O2 production in PDT and
linked the signal to the cytotoxicity, but the irradiation of laser decrease the sensitivity of the detection in vivo. During
PDT the high sensitivity probe, Fluoresceinyl Cypridina Luciferin Analog (FCLA), is used to monitor 1O2. In order to
avoid the infection of irradiation light, the delayed CL of FCLA is used to indicate 1O2. After recording the delayed CL
during PDT and scoring the skin of mice after PDT, the statistic analysis was done. The data shows a remarkable
relationship between the score and the CL. the result suggests that the CL can be used as a dose metric in vivo in PDT.
Photodynamic therapy (PDT) has gradually found its place in the treatment of malignant and
non-malignant human diseases. Currently, interstitial PDT is being explored as an alternative
modality for newly diagnosed and recurrent organ-confined prostate cancer. The interstitial
PDT for the treatment of prostate cancer might be considered to treat prostates with permanent
radioactive seeds implantation. However, the effect of implanted brachytherapy seeds on the
optical fluence distribution of PDT light has not been studied before. This study investigated, for
the first time, the effect of brachytherapy seed on the optical fluence distribution of 760 nm light
in ex vivo models (meat and canine prostate).
It is known that singlet oxygen (1O2) is the main factor mediating cytotoxicity in photodynamic therapy (PDT). The effectiveness of a PDT treatment is directly linked to the 1O2 produced in the target. Although the luminescence from 1O2 is suggested as an indicator for evaluating photodynamic therapy, the inherent disadvantages limit its potential for in vivo applications. We have previously reported that chemiluminescence can be used to detect 1O2 production in PDT and have linked the signal to the cytotoxicity. We further our investigation for monitoring 1O2 production during PDT. The lifetime of 3,7-dihydro-6-{4-[2-(N-(5-fluoresceinyl)thioureido)ethoxy]phenyl}-2-methylimidazo {1,2-a} pyrazin-3-one-chemiluminescence (FCLA-CL) is evaluated, and the results show that it is much longer than that of direct luminescence of 1O2. A gated measurement algorithm is developed to fully utilize the longer lifetime for a clean measurement of the CL without the interference from the irradiation light. The results show that it is practically feasible to use the technique to monitor the 1O2. Compared to the direct 1O2 luminescence measurement, our new technique is sensitive and can be realized with a conventional optical detector with excellent signal-to-noise ratio. It thus provides a means for real-time in vivo monitoring of 1O2 production during PDT.
Fluoresceinyl Cypridina Lucifenn Analog (FCLA) is a reactive oxygen species (ROS) specific chemiluminescence (CL)
probe. Its detection efficiency of singlet oxygen (102)couldbe significantly enhanced in the presence of human serum
albumin (HSA). The enhancement mechanism of HSA-FCLA CL is studied in the current work by means ofdirect CL
measurement and spectroscopy. The results show that, FCLA can combine with HSA. HSA is an effective 1O2
quencher. It can react with 102 and produce a protein carbonyl group with an elevated energy state. The HSA protein
carbonyl group can transfer its energy to FCLA in the FCLA-HSA complex. Via this irradiative de-excitation pathway of
the excited FCLA, luminescence production from FCLA is greatly enhanced, in addition to the chemiluminescence from
the direct interaction of FCLA and 102 FCLA has been reported for cancer diagnosis in vivo. Considering HSA is a
natural protein that is present in all parts of a human body, the efficacy of FCLA used in vivo is expected to be enhanced
through the coupling of FCLA and HSA.
Photodynamic therapy (PDT) is a cancer therapy that utilizes optical energy to activate a photosensitizer drug in a target
tissue. Always, the curative effect is dependent on the light fluence, the concentration of the photosensitizer and the
concentration of the oxygen. To date, Protophorphyrin IX (PpIX) as the only one endogenous photosensitizer is widely
used in PDT of brain tumors. Since PpIX is synthesized in intracellular structure, and is likely dependent on the phase of
the cell cycle. The cell cycle dependence of PpIX production is thus investigated in the current work in 9L gliosarcoma
cells.
Apoptosis is a very important cellular event that plays a key role in pathogeny and therapy of many diseases. In this
study, a recombinant caspase-3 substrate was used as a fluorescence resonance energy transfer (FRET) probe to detect
the activation of caspase-3, and to monitor apoptosis in human lung adenocarcinoma (ASTC-a- 1) cells. With laser
scanning confocal microscopy, we found that Photofrin were localized primarily in mitochondria, the primary targets of
Photofrin-PDT. By analyzing the dynamic changes of FRET fluorescence, the results indicate that the onset and
completion of caspase-3 activation induced by PDT is more rapidly than that by tumor necrosis factor-α (TNF-α). The
activation of caspase-3 by PDT started 20 minutes after treatment and completed in about 15 minutes. In comparison,
the onset of caspase-3 activation by TNF-a was delayed by 3 hours and the completion of caspase-3 activation required a
significantly longer time (approximately 90 minutes). These results indicated that the initiation and process of caspase-3
activation are different corresponding to different treatment methods. Our data suggest that caspase-3 activation
mediated by the cell surface death receptors is slower than that of the mitochondrial pathway and the mitochondria is an
efficient target to induce apoptosis.
Photodynamic therapy (PDT) utilizes light energy of a proper wavelength to activate a pre-administered photosensitizer
in a target tissue to achieve a localized treatment effect. Current treatment protocol of photodynamic therapy (PDT) is
defined by empirical values such as irradiation light fluence, fluence rate and the amount of administered photosensitizer.
It is well known that Singlet oxygen is the most important cytotoxic agent responsible for PDT biological effects. An in
situ monitoring of singlet oxygen production during PDT would provide a more accurate dosimeter for PDT. The
presented study has investigated the feasibility of using Fhioresceinyl Cypridina Luciferin Analog (FCLA), a singlet
oxygen specific chemiluminescence (CL) probe, as a dosimetric tool for PDT. Raji lymphoma cell suspensions were
sensitized with Photofrin(R) of various concentrations and irradiated with 635 nm laser light at different fluence rates.
FCLA-CL from singlet oxygen produced by the treatment was measured, in real time, with a photon multiplier tube
(PMT) system, and linked to the cytotoxicity resulting from the treatment. We have observed that the CL intensity of
FCLA is dependent on the PDT treatment parameters. After each PDT treatment and CL measurement, the irradiated
cells were evaluated by MIT assay for their Viability. The results show that the cell viability is highly related to the
accumulated CL. With 102 quencher, we confirmed that the CL was mainly related to PDT produced 102 The results
suggest that the FCLA-CL system can be an effective means in measuring PDT 1O2 production and may provide an
alternative dosimetry technique for PDT.
Fluoresceinyl Cypridina Luciferin Analog (FCLA) is a chemiluminescence (CL) probe for detecting reactive oxygen species (ROS). Its detection efficiency of singlet oxygen can be significantly enhanced in the presence of human serum albumin (HSA). In the current study, the mechanism of the FCLA-HSA CL system is studied by means of direct CL measurement and spectroscopy techniques. Our results show that FCLA can combine with HSA via a single binding site to form a complex. The CL efficiency of the system is largely governed by an inter-system energy transfer between the two components upon interaction with singlet oxygen. The CL production reaches maximum in a synergetic manner when equal amount of FCLA and HSA are present simultaneously, but the production is less efficient at other ratios. This suggests that the FCLA-HSA system maybe used as a singlet oxygen detecting technique with higher sensitivity compared with that of conventional CL techniques. It may also provide a potential new technique for quantitatively analyze the presence of HSA in a sample.
Photodynamic therapy (PDT) mediated with a novel vascular targeting photosensitizer pd-bacteriopheophorbide (Tookad) has been investigated as an alternative modality for the treatment of prostate cancer and other diseases. This study investigated, for the first time, the vascular photodynamic effects of Tookad-PDT on nerve tissues. We established an in situ canine model using the cutaneous branches of the saphenous nerve to evaluate the effect of Tookad-PDT secondary to vascular damage on compound-action potentials. With Tookad dose of 2 mg/kg, treatment with 50 J/cm2 induced little change in nerve conduction. However, treatment with 100 J/cm2 resulted in decreases in nerve conduction velocities, and treatment with 200 J/cm2 caused a total loss of nerve conduction. Vasculature surrounding the saphenous nerve appeared irritated. The nerve itself looked swollen and individual fibers were not as distinct as they were before PDT treatment. Epineurium had mild hemorrhage, leukocyte infiltration, fibroplasias and vascular hypertrophy. However, the nerve fascicles and nerve fibers were free of lesions. We also studied the effect of Tookad-PDT secondary to vascular damage on the pelvic nerve in the immediate vicinity of the prostate gland. The pelvic nerve and saphenous nerve showed different sensitivity and histopathological responses to Tookad-PDT. Degeneration nerve fibers and necrotic neurons were seen in the pelvic nerve at a dose level of 1 mg/kg and 50 J/cm2. Adjacent connective tissue showed areas of hemorrhage, fibrosis and inflammation. Our preliminary results suggest that possible side effects of interstitial PDT on prostate nerve tissues need to be further investigated.
Photoacoustic tomography is a potential and noninvasive medical imaging technology. It combines the advantages of pure optic imaging and pure ultrasound imaging. Photoacoustic signals induced by a short pulse laser cover a wide spectral range. We have explored the frequency spectrum of absorbers with different sizes and the influence of photoacoustic signals with different spectral components on photoacoustic imaging. The simulations and experiments demonstrated that the major frequency ranges of photoacoustic pressures of absorbers with diameters of ~cm, ~mm and hundreds of mm are about 20kHz~300kHz, 70kHz~2.5MHz and 400kHz~20MHz, respectively. The low spectral components of photoacoustic signals contribute to the non-boundary region of absorbers, and the high spectral components contribute to small structures, especially, to boundaries. It suggests that the ultrasonic transducers used to detect photoacoustic pressures should be designed and selected according to the frequency ranges of absorbers.
Photoacoustic imaging combines the contrast advantage of pure optical imaging and the resolution advantage of pure ultrasonic imaging. It has become a popular research subject at present. A fast photoacoustic imaging system based on multi-element linear transducer array and phase-controlled focus method was developed and tested on phantoms and tissues. A Q switched Nd:YAG laser operating at 532nm was used in our experiment as thermal source. The multi-element linear transducer array consists of 320 elements. By phase-controlled focus method, 64 signals, one of which gathered by 11-group element, make up of an image. Experiment results can map the distribution of the optical absorption correctly. The same transducer array also can operate as a conventional phase array and produced ultrasound imaging. Compared to other existing technology and algorithm, the PA imaging based on transducer array was characterize by speediness and convenience. It can provide a new approach for tissue functional imaging in vivo, and may have potentials in developing into an appliance for clinic diagnosis.
Photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (pd-bacteriopheophorbide), was investigated as an alternative treatment modality for prostate cancer. Tookad photodynamic effects on the prostate and its adjacent tissues were evaluated in canine models. Interstitial prostate PDT was performed by irradiating individual lobes with a diode laser (763 nm) and 1-cm cylindrical diffuser fibers at various light doses to activate the IV administered photosensitizer Tookad (1 - 2 mg/kg). The sensitivity of the adjacent tissues to Tookad-PDT was determined by superficially irradiating the surfaces of the bladder, colon, abdominal muscle and pelvic plexus with a microlens fiber at various drug/light doses. PDT effect on the prostatic urethra was evaluated by transurethral irradiation. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathologic examination. At one-week post interstitial prostate PDT, the animals recovered well with little or no urethral complications. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. The bladder, colon, abdominal muscle and pelvic plexus, appeared to also be sensitive to Tookad-PDT at light dose levels greater than 40 Jcm2. Urethral mucosa appeared less sensitive to Tookad-PDT. In conclusion, Tookad-mediated PDT demonstrates very strong vascular effects and can provide an effective alternative for the treatment of localized prostate cancer. Protection of the adjacent tissues should be taken into consideration in the total prostate ablation process due to their sensitivity to the Tookad-mediated PDT.
Apoptosis is one of the important modes in PDT-induced cell death. Activation of caspase-3 is considered to be the final step in many apoptosis pathways. In this study, we used SCAT3, a fluorescence resonance energy transfer (FRET) probe containing caspase-3 substrate, to study the dynamics of caspase-3 activation in living ASTC-a-1 cells expressing stably SCAT3. The FRET analysis results indicated that caspase-3 activation in response to tumor necrosis factor-α or PDT resulted in cleavage of the linker peptide and subsequent disruption of the FRET signal. The SCAT3 was cleaved immediately after PDT treatment, but that for TNF-a treatment was delayed two hours. Our experimental results suggested that the different apoptotic pathways induced by TNF-α or PDT caused different cleavage kinetics of SCAT3. This study shows that FRET technique based on GFPs could be used to study the mechanism of PDT-induced apoptosis in living cells.
A new method for identification of point mutations was proposed. Polymerase chain reaction (PCR) amplification of a sequence from genomic DNA was followed by digestion with a kind of restriction enzyme, which only cut the wild-type amplicon containing its recognition site. Reaction products were detected by electrochemiluminescence (ECL) assay after adsorption of the resulting DNA duplexes to the solid phase. One strand of PCR products carries biotin to be bound on a streptavidin-coated microbead for sample selection. Another strand carries Ru(bpy)32+ (TBR) to react with tripropylamine (TPA) to emit light for ECL detection. The method was applied to detect a specific point mutation in H-ras oncogene in T24 cell line. The results show that the detection limit for H-ras amplicon is 100 fmol and the linear range is more than 3 orders of magnitude, thus, make quantitative analysis possible. The genotype can be clearly discriminated. Results of the study suggest that ECL-PCR is a feasible quantitative method for safe, sensitive and rapid detection of point mutation in human genes.
It has been proved that singlet oxygen is the major cytotoxic agent in Photodynamic therapy (PDT). Chemiluminescence(CL) mediated with Cyp- ridina luciferin analog (FCLA) was recently reported to successfully detect singlet oxygen in chemical and biological systems. The present study has focused on establishing the experiment conditions of FCLA-assisted CL method and tested the validity of the system as a dosimetric tool for PDT in vitro. HL-60 leukemia cell suspensions were sensitized with varying dose of Photofrin and irradiated with 635nm laser light at different rate. The FCLA-CL associated with singlet oxygen was measured with a band-pass filtered photon multiplier tube (PMT) system. We have observed that the CL intensity of FCLA is dependent on PDT treatment parameters. In addition, Cell survival corresponded strongly with peak CL intensity. These results suggest that the FCLA-assisted CL system can be an effective means in in vitro PDT study as an indicator of reactive oxygen species. The system may as well, with additional investigations, provide an alternative dosimetry technique for PDT.
Photodynamic therapy (PDT) is a cancer therapy that utilizes optical energy to activate a photosensitizer drug in a target tissue. Reactive oxygen species (ROS), such as 1O2 and superoxide, are believed to be the major cytotoxic agents involved in PDT. Although current PDT dosimetry mostly involves measurements of light and photosensitizer doses delivered to a patient, the quantification of ROS production during a treatment would be the ultimate dosimetry of PDT. Technically, it is very difficult and expensive to directly measure the fluorescence from 1O2, due to its extreme short lifetime and weak signal strength. In this paper, Photofrin(R) and 635nm laser were used to generate 1O2 and superoxide in a PDT in solution. Compound 3,7- dihydro-6-{4-[2-(N’-(5-fluoresceinyl) thioureido) ethoxy] phenyl}-2- methylimidazo{1,2-a} pyrazin-3-one sodium salt,an Cyp- ridina luciferin analog commonly referred as FCLA, was used as a chemical reporter of ROS. The 532nm chemiluminescence (CL) from the reaction of the FCLA and ROS was detected with a photon multiplier tube (PMT) system operating at single photon counting mode. With the setup, we have made detections of ROS generated by PDT in real time. By varying the amount of conventional PDT dosage (photosensitizer concentration, light irradiation fluence and its delivery rate) and the amount of FCLA, the intensity of CL and its consumption rate were investigated. The results show that the intensity and temporal profile of CL are highly related to the PDT treatment parameters. This suggests that FCLA CL may provide a highly potential alternative for ROS detection during PDT.
Photodynamic therapy (PDT) is a novel and promising cancer treatment that employs a combination of a photosensitizing chemical and visible light, induces apoptosis in cell, and activation of caspase-3 is considered to be the final step in many apoptosis pathways. The changes of caspase-3 activation in cell during TNFα- and photodynamic therapy-induced apoptosis was measured by fluorescence resonance energy transfer (FRET) analysis. FRET probe consisting of fusions of an enhanced cyan fluorescent protein (ECFP), Venus and a linker peptide containing the caspase-3 cleavage sequence DEVD was utilized. Therefore, activated caspase-3 cleaved the linker peptide of FRET probe and disrupted the FRET signal. Human lung adenocarcinoma cell line (ASTC-a-1) were stably transfected with the plasmid (ECFP-DEVD-Venus) and then were treated by TNF-α and PDT, respectively. Experimental results indicated that caspase-3 activation resulted in cleavage of linker peptide and subsequent disruption of the FRET signal during TNFα- and photodynamic therapy-induced apoptosis, and that the activation of caspase-3 induced by photodynamic therapy was faster than that induce by TNF-α. The study supports that using FRET technique and different recombinant substrates as FRET probes could be used to detect the process of PDT-induced apoptosis and provide a new means to investigate apoptotic mechanism of PDT.
In this pre-clinical study, photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (palladium-bacteriopheophorbide) is investigated as an alternative treatment modality for the ablation of prostate cancer. Canine prostate was used as the animal model. PDT was performed by interstitially irradiating the surgically exposed prostates with a diode laser (763 nm) to activate the IV infused photosensitizer. The effects of drug dose, drug-light interval, and light fluence rate on PDT efficacy were evaluated. The prostates and adjacent tissues were harvested at one-week post PDT and subjected to histopathological examination. The dogs recovered well with little or no urethral complications. Urinalysis showed trace blood. Histological examination showed minimal damage to the prostatic urethra. These indicated that the urethra was well preserved. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis with a clear demarcation. Maximum lesion volume of ~3 cm3 could be achieved with a single 1-cm diffuser fiber at a dose level of 1 mg/kg and 200 J/cm, suggesting the therapy is very effective in ablating prostatic tissue. PDT induced lesion could reach the capsule layers but adjacent tissues were well preserved. The novel photosensitizer is a vascular drug and cleared rapidly from the circulation. Light irradiation can be performed during drug infusion thereby eliminating waiting time. The novel vascular acting photosensitizer Tookad-mediated PDT could provide an effective alternative to treat prostate cancer.
In photodynamic therapy (PDT), a target tissue with pre-administered photosensitizer is exposed to laser light. The photochemical process produces reaction oxygen species (ROS), such as singlet oxygen and superoxide, and leads to ultimate cell death. A direct monitoring of ROS production during PDT, thus, may provide important information in both basic science and clinical practice. A cypridina luciferin analogue (FCLA) is a chemiluminescence (CL) probe that selectively detects singlet oxygen and superoxide. In this study, FCLA was used as an optical reporter of ROS produced by photosensitization reaction of Photofrin in Hanks solution and the CL was measured by a photomultiplier system operated at single photon counting mode. By varying the amount of PDT dosage (photosensitizer dose, light irradiation fluence rate) and the amount of FCLA, the intensity of CL were investigated. The results showed the FCLA concentration affects the ratio of the signal to background CL. The decay time of the photosensitized CL was approximately 10 sec., after the excitation source was turned off. In addition, the intensity of the CL-FCLA increased with increasing concentration of Photofrin and fluence rate. The work supported the potential application of FCLA-chemiluminescence probe as a dosimetric tool for PDT.
A novel method of photodynamic diagnosis (PDD) of cancer mediated by chemiluminescence (CL) probe is presented. The mechanism for photodynamic therapy (PDT) involves reactive oxygen species (ROS), such as singlet oxygen (1O2) and superoxide (O2-), generated by during the photochemical process. Both 1O2 and O2- can react with Cypridina luciferin analogue (FCLA), a highly selective CL probe for detecting the ROS. Chemiluminescence from the reaction of FCLA with the ROS, at about 530 nm, was detected by a highly sensitive ICCD system. The CL was markedly inhibited by the addition of 10 mmol/L sodium azide (NaN3) in a sample solution. Similar phenomena, with lesser extents of changes, were observed at the additions of 10 μmol/L superoxide dismutase (SOD), 10 mmol/L mannitol, and 100 μg/mL catalase, respectively. This indicates that the detected CL signals were mainly from ROS generated during the photosensitization reactions. Also, the chemiluminescence method was used to detect the ROS during sonodynamic action, both in vitro and in vivo. ROS formation during sonosensitizations of HpD and ATX-70 were detected using our newly-developed imaging technique, in real time, on tumor bearing animals. This method can provide a new means in clinics for tumor diagnosis.
Photodynamic therapy (PDT) utilizes photon energy to activate a pre-administered photosensitizer drug in tissue to achieve a localized tumor control. PDT cell killing mechanism is directly related to the reactive oxygen species (ROS) produced during the photochemical reactions. Conventional PDT dosimetry evaluates distributions of the photosensitizer drug, photon propagation and absorption, and availability of molecular oxygen in the target tissue. Yet, the ultimate bullet for the damaging effect is ROS. An evaluation of ROS production during PDT should provide a more direct marker for PDT. Fluoresceinyl Cypridina Luciferin Analog (FCLA) is a chemiluminescence probe that specifically interacts with ROS (singlet oxygen and/or superoxide). The work is a preliminary investigation of the feasibility using FCLA as a means to evaluate ROS production in PDT.
Photodynamic therapy (PDT) mediated with vascular acting photosensitizer pd-bacteriopheophorbide (Tookad),
is investigated as an alternative modality for the total ablation of prostate cancer. In vivo normal canine prostate is used as the animal model. Interstitial PDT was performed by irradiating the surgically exposed prostates with a diode laser (763 nm, 150 mW/cm) to activate the IV infused photosensitizer drug. The prostate and its adjacent tissues were harvested and subjected to histopathological examination. At one-week post PDT, the animals recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. Prostate lesions could be detected by MRI scan as early as 48 h post PDT. Maximum lesion size of 1.5 cm3 and 2.9 cm3 could be achieved at 50 J/cm and 100 J/cm, respectively, with interstitial treatment using a single 1-cm diffuser fiber, suggesting the Tookad-PDT is very effective in ablating prostatic tissue. Pharmacokinetic studies show that the photosensitizer is cleared rapidly from the circulation. In conclusion, the novel photosensitizer Tookad mediated PDT may provide an effective alternative to treat localized prostate cancer.
Photodynamic therapy (PDT) mediated with vascular acting photosensitizer pd-bacteriopheophorbide (Tookad), is investigated as an alternative modality for the total ablation of prostate cancer. Invivo normal canine prostate is used as the animal model. Interstitial PDT was performed by irradiating the surgically exposed prostates with a diode laser (763 nm, 150 mW/cm) to activate the i.v. infused photosensitizer drug. The effects of two-session PDT were evaluated. The prostate and its adjacent tissues were harvested and subjected to histopathological examination. At one-week, post second-session PDT, the animals recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. Two-session PDT or one single session PDT induced a similar extent of damage. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. Maximum lesion size of over 3 cm in dimension could be achieved with a single 1-cm interstitial treatment, suggesting the therapy is very effective in ablating prostatic tissue. Pharmacokinetic studies show that the photosensitizer is cleared rapidly from the circulation. In conclusion, the novel photosensitizer Tookad mediated PDT may provide an effective alternative to treat prostate cancer.
Tumor hypoxia, either pre-existing or as a result of oxygen bleaching during Photodynamic Therapy (PDT) light irradiation, can significantly reduce the effectiveness of PDT induced cell killing. To overcome the effect of tumor hypoxia and improve tumor cell killing, we propose using supplemental hyperoxygenation during Photofrin PDT. Our previous study has demonstrated that, in an in vivo model, tumor control can be improved by normobaric or hyperbaric 100% oxygen supply. The mechanism for the tumor cure enhancement of the hyperoxygenation-PDT combined therapy is investigated in this study by using an in vivo/in vitro technique. A hypoxic tumor model was established by implanting mammary adenocarcinoma (MCA) in hind legs of C3H mice. Light irradiation (200 J/cm2 at either 75 or 150 mW/cm2), under various oxygen supplemental conditions (room air or carbogen or 100% normobaric or hyperbaric 100% oxygen), was delivered through an optical fiber with a microlens to animals who received 12.5 mg/kg Photofrin 24 hours prior to light irradiation. Tumors treated with PDT were harvested and grown in vitro for colony formation analysis. Treated tumors were also analyzed histologically. The results show that, when combined with hyperoxygenation, the cell killing rate immediately after a PDT treatment is significantly improved over that treated without hyperoxygenation, suggesting an enhanced direct cell killing. This study further confirms our earlier observation that when a PDT treatment is combined with hyperoxygenation, it can be more effective in controlling hypoxic tumors. H&E stain revealed that PDT induced tumor necrosis and hemorrhage. In conclusion, by using an in vivo/in vitro assay, we have shown that PDT combined with hyper-oxygenation can enhance direct cell killing and improve tumor cure.
In this study, photodynamic therapy (PDT) mediated with a novel, second generation photosensitizer Tookad (palladium-bacteriopheophorbide, WST09, STEBA Biotech, France), is investigated as an alternative modality in the treatment of prostate cancer. In vivo normal canine prostate and spontaneous advanced prostate cancer are used as the animal model. PDT was performed by irradiating the surgically exposed prostates with a diode laser (763 nm, 150 mW/cm) to activate the i.v. infused photosensitizer. The effects of drug concentration, drug-light interval, and light fluence rate on the PDT efficacy were studied. The prostates and adjacent tissues (bladder and underlying colon) were harvested and subjected to histopathological examination. During the one-week to 3-month period post PDT treatment, the dogs recovered well with little or no urethral complications. Prostatic urethra and prostate adjacent tissues (bladder and underlying colon) were well preserved. Light irradiation delivered during drug infusion or within 15 min post drug infusion induced the similar extend of damages. PDT induced prostate lesions in both normal and cancerous prostate were characterized by marked hemorrhagic necrosis and atrophy. Maximum lesion size of over 3 cm in dimension could be achieved with a single 1-cm interstitial treatment, suggesting the therapy is very effective in ablating cancerous prostatic tissue. In conclusion, the second generation photosensitizer Tookad mediated PDT may provide an effective alternative to treat prostate cancer.
PDT in prostate cancer will likely be implemented clinically with patients who have failed prior ionizing radiation therapy (RT). The current study is to develop an in vivo model to evaluate the effects of PDT on prostatic tissue after RT. To produce a physiological and anatomical environment in prostate similar to that in patients who have failed RT, canine prostates (n=4) were subjected to a definitive course of ionizing radiation therapy (2.7 Gy x 20 fractions) 5 to 6 months prior to PDT. A laparotomy was performed to expose the prostate for PDT. Second generation photosensitizer Tookad (Palladium-Bacteriopheophorbide, Steba Biotech, The Netherlands) acts primarily on tissue vasculature and is very effective in destroying normal prostatic tissue, as shown by our prior studies. Due to the extremely fast clearance of the photosensitizer, interstitial light irradiation (760 nm, 50-200 J/cm, 150 mW/cm from a 1 cm diffuser fiber) was delivered 4 minutes after the onset of Tookad infusion (i.v. 2.5 mg/ml, 2 mg/kg, total infusion time 10 min). The prostates were harvested for histopathology one week after PDT. At one week, the lesions were characterized by acute hemorrhagic necrosis with patchy sub-capsular hyperemia and edema. The maximum lesion diameter for 50, 100 and 200 J/cm PDT was approximately 15, 20 and 28 mm, respectively. The lesion size is well correlated with light fluence and comparable to that in prostates treated with identical PDT doses but without prior-RT. Under light-microscopy, the PDT induced necrosis is clearly distinguishable from the radiation induced fibrosis. No urethral lesions were observed. Dyer’s Verhoeff stain showed the loss of stromal connective tissue and the acinar collagen in the PDT treated area. There was no noticeable damage on the bladder or underlying colon section. In conclusion, Tookad-PDT can effectively destroy prostate tissue with prior-RT induced fibrosis, thus, may provide an alternative modality for those prostate-cancer patients who have failed RT.
Photodynamic therapy (PDT) requires molecular oxygen during light irradiation in order to generate reactive oxygen species. Tumor hypoxia, either pre-existing or induced by PDT, can severely hamper the effectiveness of PDT treatment. Lowering the light irradiation dose rate or fractionating a light dose may improve cell kill of PDT induced hypoxic cells, but will have no effect on pre-existing hypoxic cells. In this study, hyper-oxygenation technique was used during PDT to overcome hypoxia. C3H mice with transplanted mammary carcinoma tumors were injected with 12.5 mg/kg Photofrmn and irradiated with 630 nm laser light 24 hours later. Tumor oxygenation was manipulated by subjecting the animals to 3 alp hyperbaric oxygen or normobanc oxygen during PDT light irradiation. The results show a significant improvement in tumor response when PDT was delivered during hyper-oxygenation. With hyper-oxygenation, up to 80% of treated tumors showed no re-growth after 60 days. In comparison, only 20% of tumors treated while animals breathed room air did not re-grow. To explore the effect of hyperoxygenation on tumor oxygenation, tumor PO2 was measured with microelectrodes positioned in pre-existing hypoxic regions before and during the PDT. The results show that hyperoxygenation may oxygenate pre-existing hypoxic cells and compensate for oxygen depletion induced by PDT light irradiation. In conclusion, hyper-oxygenation may provide effective ways to improve PDT treatment efficiency by oxygenating both pre-existing and treatment induced cell hypoxia.
Paul Muller, Brian Wilson, Lothar Lilge, Victor Yang, Abhay Varma, Arjen Bogaards, Fred Hetzel, Qun Chen, Tim Fullagar, Robert Fenstermaker, Robert Selker, Judith Abrams
In our previous phase II studies we treated 112 patients with malignant brain tumors with 2-mg/kg Photofrin i.v. and intra-operative cavitary PDT. We concluded that PDT was safe in patients with newly diagnosed or recurrent supratentorial malignant gliomas. Pathology, performance grade and light dose were significantly related to survival time. In selected patients when an adequate light dose was used survival time improved. The surgical mortality rate was less than 3%. [spie 2000] We have initiated two randomized prospective trials - the first, to determine if the addition of PDT to standard therapy [surgery, radiation and/or chemotherapy] prolongs the survival of patients with newly diagnosed malignant astrocytic tumors; and the second, to determine whether high light dose PDT [120 J/cm2] is superior to low light dose PDT [40 J/cm2] in patients with recurrent malignant astrocytic tumors. To date, 158 patients have been recruited - 72 to the newly diagnosed malignant glioma study and 86 to the recurrent glioma study. In the recurrent glioma study we compared the pre-operative KS and elements of the neurological examination [speech function, visual fields, cognitive function, sensory examination and gait] to the post-operative examinations at hospital discharge. The means were compared by paired student-t test. The KS in 86 of 88 patients with recurrent gliomas were assessable. The mean [s.d.] preoperative and post-operative KS were 82+/- 14 and 79+/- 17, respectively [p=0.003]. The mean decline in KS, although statistically significant, was small and of no clinical importance. The median Karnofsky score changed from 90 to 80. The KS improved in 8 patients; their post-operative average length of stay (alos) was =9.7 days. There was no change in 47 [alos=8.3], a decline of 10 points in 24 [aloc=13.4] and declined by more than 10 points in 7 [alos=23.3]. Three of these 7 patients who had a decline of >10 points improved in follow-up but did not reach their preoperative KS. The data were not available in 2. Elements of the preoperative and discharge neurological examination were assigned a score and compared by a paired t-test. There was a statistically insignificant improvement in the neurological score. A small but statistically significant decline in Karnofsky score was identified post-operatively in these recurrent tumor patients. Their hospital average length of stay increased with declining Karnofsky score. These prospective clinical observations confirmed our previous conclusion that brain tumor PDT was safe. The clinical studies are supported in part by grant CA 43892 awarded by DHHS/NIH/NCI.
Photodynamic therapy (PDT) utilizes optical energy to activate a pre-administered photosensitizer drug to achieve a localized tumor control. In the presented study, PDT mediated with a second-generation photosensitizer, WST09 (TOOKAD, Steba Biotech, The Netherlands), is investigated as an alternative therapy in the treatment of prostate cancer. In vivo canine prostate is used as the animal model. PDT was performed by irradiating the surgically exposed prostates both superficially and interstitially with a diode laser (763 nm) to activate the intra-operatively i.v. infused photosensitizer. During light irradiation, tissue optical properties, and temperature were monitored. During the one-week to 3-month period post PDT treatment, the dogs recovered well with little or no complications. The prostates were harvested and subjected to histopathological evaluations. Maximum lesion size of over 3 cm in dimension could be achieved with a single treatment, suggesting the therapy is extremely effective in destroying prostatic tissue. Although we found there was loss of epithelial lining in prostatic urethra, there was no evidence it had caused urinary tract side effects as reported in those studies utilizing transurethral irradiation. In conclusion, we found second generation photosensitizer WST09 mediated PDT may provide an excellent alternative to treat prostate cancer.
Tumor hypoxia, either pre-existing or as a result of oxygen bleaching during PDT light irradiation, can significantly reduce the effectiveness of a PDT treatment. To overcome the effect oftumor hypoxia, we propose using supplemental hyperoxygenation during a PDT treatment. The mechanism for the tumor cure enhancement ofthe combined therapy is investigated in the study by using an in vivo/in vitro assay. Tumors treated with PDT/hyperoxygenation are harvested at various times after the light irradiation and cultured in vitro for colony formation, thus separating the direct cell killing by PDT and secondary vascular effect. The results show that, when combined with hyper-oxygenation, the cell survival (colony formation) rate immediately after a PDT treatment is significantly improved over that treated without hyper-oxygenation, suggesting an enhanced direct cell killing. Cell survival rates were unchanged for the first 4 hours after a PDT treatment, but decreased significantly at 1 8 hours, suggesting that secondary vascular damage did take effect, but not until a period of at least 4 hours after light irradiation. These results further confirm our earlier observation that when a PDT treatment is combined with hyper-oxygenation, it can be more effective in controlling hypoxic tumors.
In a phase II trial we treated more than 100 patients with malignant brain tumors with 2-mg/kg Photofrin iv. and intraoperative cavitary PDT. We concluded that PDT was safe in patients with newly diagnosed or recurrent supratentorial malignant gliomas. Regression analysis showed that pathology, performance grade and light dose were significantly related to survival time. We identified a prolongation of survival in selected patients when an adequate light dose was used. The surgical mortality rate was less than 3%. We have initiated two randomized prospective trials - the first, to determine if the addition of PDT to standard therapy [surgery, radiation and/or chemotherapy] prolongs the survival of patients with newly diagnosed malignant astrocytic tumors; and the second, to determine whether high light dose PDT [120 J/cm2] is superior to low light dose PDT [40 J/cm2] in patients with recurrent malignant astrocytic tumors. In the first 20 months of these clinical studies, 90 patients have been recruited. There were 52 in the recurrent study and 37 in the newly diagnosed study. 64% of the tumors were glioblastoma and 23% malignant astrocytoma or malignant mixed glioma. In the trial of newly diagnosed tumors 17 were randomized to surgery with a mean age of 58 ! 2.9 [sem] and 20 to surgery plus PDT with a mean age of 54 ! 2.5. In recurrent glioma trial 26 were randomized to low light dose PDT [mean age 48.1 ! 2.7] and 26 to high light dose [age 52 ! 2.7]. An update of our phase 2 data and a description of brain tumor PDT techniques is presented below. The clinical studies are supported in part by grant CA 43892 awarded by DHHS/NIH/NCI.
Paul Muller, Brian Wilson, Lothar Lilge, Victor Yang, Mike Hitchcock, Fred Hetzel, Qun Chen, T. Fullager, Robert Fenstermaker, Robert Selker, Judith Abrams
Photodynamic therapy (PDT) is a local treatment for malignment tumors. In a phase 2 trial in patients with supratentorial gliomas treated with 2 mg/kg Photofrin i.v. and intraoperative cavitary PDT, we were able to conclude that PDT was safe in patients with either newly diagnosed or recurrent supratentorial malignant gliomas. There appears to be prolongation of survival in selected patients when an adequate light dose is used. The surgical mortality rate was less than 3 percent.
Photodynamic therapy (PDT) requires tissue oxygenation during light irradiation. Tumor hypoxia, either pre-existing or induced by PDT during light irradiation, can severely hamper the effectiveness of a PDT treatment. Lowering the light irradiation does rate or fractionating a light dose may improve cell kill of PDT induced hypoxic cells, but will have no effects on pre-existing hypoxic cells. In the current study, we used hyper-oxygenation during PDT to overcome cell hypoxia in PDT. C3H mice with transplanted mammary carcinoma tumor were injected with 12.5 mg/kg Photofrin and irradiated with 630 nm laser light 24 hours later. Tumor oxygenation was manipulated by subjecting the animals to 3 a.t.p. hyperbaric oxygen or normobaric oxygen during PDT light irradiation. The results show a significant improvement in tumor response when PDT was delivered during hyper-oxygenation. With hyper-oxygenation, up to 80% of treated tumors showed no re-growth after 60 days. In comparison, only 20% of tumors treated while animals breathed normal room air, did not re-grow. To quantitatively evaluate the effects of manipulating tumor oxygenation, tumor p02 was measured with microelectrodes positioned in pre-existing hypoxic regions before and during the PDT light irradiation. The results show that hyper-oxygenation may oxygenate pre-existing hypoxic cells and compensate oxygen depletion induced by PDT light irradiation. In conclusion, hyper-oxygenation may provide effective ways to improve PDT treatment efficiency by oxygenating both pre-existing and treatment induced cell hypoxia.
Photodynamic therapy (PDT) is rapidly becoming an accepted therapeutic modality for the treatment of some types of malignant tumors. An important feature of PDT is its absolute dependence on molecular oxygen during light irradiation.Hypoxic tumor cells, either pre-existing or photochemically depleted of their oxygen supply during light irradiation, are resistant to PDT treatment, and contribute to treatment failures. We hypothesize that tumor response to PDT can be improved by combining PDT with Hyper-oxygenation, which may simultaneously compensate for the oxygen depletion by PDT and increase oxygenation of the pre-existing hypoxic cells. The doubling time of mammary carcinoma tumors, implanted in either leg or flank of C3H mice, was evaluated after PDT treatment with/without addition of hyperoxygenation. By adding hyperoxygenation to a non- curative PDT dose, a further delay in the tumor regrowth was observed. For a sub-curative does PDT treatment, the addition of hyperoxygenation resulted in an increase in tumor cure. The results indicate that tumor response can be improved by combining PDT and hyperoxygenation.
Prior to a possible clinical application of photodynamic therapy (PDT) for prostatic diseases such as benign prostatic hyperplasia and prostate cancer, optical properties of the prostate gland need to be studied. The specific objectives of this study were (1) to determine the light penetration depth, (2) to document the photosensitizer levels in the prostate, and (3) to document the lesion size after PDT. Sixteen dogs were injected with Photofrin II (1, 3 and 5 mg/kg) 24 hrs prior to laser application. After laparotomy and exposure of prostate, monochromatic light (630 nm, via an argon pumped dye laser) was applied through an isotropic fiber at 100 mw for a total dose of 400 joules. Continuous light fluence and temperature were documented. Prostates were harvested at 1 week and examined histologically for the lesion size. Four sham dogs were treated without Photofrin II. At Photofrin doses of 1, 3 and 5 mg/kg the mean prostatic Photofrin levels were 1.78 plus or minus 0.33, 1.47 plus or minus 0.08 and 1.95 plus or minus 0.44 (mu) gm/ml. The mean light penetration depths were 2.08, 1.37 and 1.64 mm respectively. Photofrin dose escalation (1, 3 and 5 mg/kg) increased the lesion size to radius of 4.1 plus or minus 0.9 mm, 4.4 plus or minus 0.8 mm and 6.3 plus or minus 0.9 mm. There were no lesions seen in sham dogs. These results demonstrate that light penetration in prostate is consistent and therapeutic levels of photosensitizer are achieved in prostatic tissue. Moreover, increasing size of the lesions were documented with dose escalation.
High powered lasers have been used in dermatological procedures such as tattoo removal. This use is associated with a potential, biological hazard of high speed tissue particles from the laser field. It has been proposed that by applying a clear dermatological would dressing directly over the laser treatment site, it may be possible to completely trap the potentially airborne tissue particles from the procedure. Some important questions must be addressed prior to the implementation of such a technique. While the use of a wound dressing may significantly reduce the airborne materials during the laser procedures, new problems may arise: 1 . The wound dressing or some of its components may absorb excessive amount of light energy. This would result in a very localized temperature rise which may be harmful to the patient; 2. The smooth surface of the wound dressing material could induce specular reflection of the incident laser beam, thus introducing a laser hazard to the staff and patient. To address these possible problems, we studied a series of ClearSite Wound Dressings which have been reportedly tested for such laser procedures. The objective of the studies were, to determine if the use of ClearSite in conjunction with laser procedures poses a possible hazard to either the patient or to the Operating Room personnel, and to determine the effect of the ClearSite dressing on the optical characteristics of the light beam. The latter includes light absorption and transmittance for various wavelengths.
To provide basic scientific information for utilizing photodynamic therapy to treat prostatic carcinoma, PDT dosimetry and effective treatment volume were investigated using canine prostate as an in vivo animal model. The prostate glands were surgically exposed. Isotropic tip fibers were inserted into the gland for either light irradiation or detection. PDT doses of 400 J and 1, 3 or 5 mg/kg Photofrin were used for single fiber irradiation treatments. All animals were terminated at 1 week and the prostates evaluated histopathologically. The results show that the lesion size was dependent on the treatment dose. The maximum lesion dimension was approximately 1.6 cm. The data acquired from the single fiber irradiation study were then used to plan for multi-fiber interstitial PDT treatments with a goal of achieving a larger treatment volume for practical purpose. The data indicate that the lesion size from the multiple fiber treatment could be predicted based on the single fiber treatment with the light pattern summed from all sources.
The objective of this study is to investigate tumor responses when treated with the combination of photodynamic therapy and hyperthermia. Intra-tumoral oxygen levels (pO2) and 30 day tumor regrowth were investigated. C3H murine mammary leg tumors were implanted and grown to a diameter of 6 mm. The combined treatment was designed based on the data from our previous studies of tumor response and tumor tissue oxygen levels after various doses of hyperthermia and PDT alone. Photofrin (12.5 mg/kg, i.p.) was administered to the animals 24 hours before light treatment (630 nm, 200 J/cm2, 300 mW/cm2). Hyperthermia (43.5 degree(s)C, 30 to 90 minutes) was delivered 4 hours after the PDT treatment. TCD60 and TCD80 were observed for the combined therapy with 60 and 90 min hyperthermia, in comparison to the TCD10 and TCD20 for the hyperthermia alone, respectively. The results indicate that improved therapeutic results can be achieved with the combined therapy designed based on the tissue PO2 profiles after single modality treatment.
A new modality of interstitial therapy to treat prostate cancer using photodynamic principles has been studied in a canine model. The effect of interstitial application of monochromatic light from an argon pumped dye laser at 630 nm was studied in a canine model. No significant hyperthermia was seen during the treatment. A concentric zone around the treatment fiber was seen during the treatment. A concentric zone around the treatment fiber was seen in PDT treated dogs and the maximum size was 18 mm. The data suggests that PDT may be clinically applicable in achieving tissue necrosis using interstitial light application in a solid organ like prostate.
The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.
Different aspects of photodynamic therapy in normal rat brain tissue have been studied, in an effort to understand and improve the dosimetry of this new modality in treatment of brain tumors. dosimetry parameters, including light energy dose, fluence rate and beam size, and drug dosage were studied. PDT induced lesion depth in brain was measured as a biological endpoint. Effective attenuation depth and absolute light fluence rate distribution under superficial irradiation were measured using invasive optical probes. Photosensitizer uptake was quantified using HPLC analysis. The results indicate that normal brain have a high intrinsic sensitivity to PDT treatment, based on the estimated photodynamic threshold.
Investigation is made of the optical attenuation depth in Fisher rat brain at different wavelengths and during PDT treatment. The attenuation depth gradually increased from 0.6 to 1.7 mm when the irradiating light wavelength increased from 450 nm to 710 nm. During PDT treatment (Photofrin II 48 hours prior to 633 nm, 5 mm diameter surface irradiation of 100 J/cm2 and 100 mW/cm2), the attenuation depth was found relatively constant (variation
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.