Prof. Summer L. Gibbs Profile

Prof. Summer L. Gibbs

Professor at Oregon Health & Science Univ

SPIE Involvement:

Conference Chair | Author | Editor

Publications (69)

SPIE Journal Paper | 29 October 2024 Open Access

Two-color fluorescence-guided surgery for head and neck cancer resections

Dani Szafran-Reeder, Nourhan Shams, Antonio Montaño, Syed Zaki Husain Rizvi, Adam W.G. Alani, Kimberley Samkoe, Lei Wang, Summer Gibbs

JBO, Vol. 30, Issue S1, S13707, (October 2024) https://doi.org/10.1117/12.10.1117/1.JBO.30.S1.S13707

KEYWORDS: Tumors, Nervous system, Nerve, Cancer, Surgery, Near infrared, Neck, Fluorescence imaging, Resection, Head

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Proceedings Article | 13 March 2024 Presentation

In situ therapeutic response imaging using a novel fluorescence imaging platform: TRIPODD

Nathan McMahon, Allison Solanki, Lei Wang, Antonio Montaño, Summer Gibbs

Proceedings Volume PC12846, PC1284604 (2024) https://doi.org/10.1117/12.3000414

KEYWORDS: Tumors, Image segmentation, Tissues, Cell death, Proteins, Fluorescence imaging, Cancer, Resistance, Tumor growth modeling, Tolerancing

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Proceedings Article | 13 March 2024 Presentation

Development of near-infrared fluorophores for improved nerve-sparing surgical procedures

Lei Wang, Connor Barth, Antonio Montaño, Anas Masillati, Dani Szafran, Summer Gibbs

Proceedings Volume PC12862, PC1286205 (2024) https://doi.org/10.1117/12.3003618

KEYWORDS: Nerve, Fluorophores, Near infrared, Visualization, Surgery, Nervous system, Injuries, Imaging systems, Contrast agents, Real time imaging

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Proceedings Article | 13 March 2024 Presentation

Can near infrared nerve-specific imaging assess nerve integrity?

Anas Masillati, Antonio Montaño, Connor Barth, Lei Wang, Summer Gibbs

Proceedings Volume PC12825, PC128250I (2024) https://doi.org/10.1117/12.3004839

KEYWORDS: Nerve, Injuries, Fluorophores, Surgery, Visualization, Near infrared, Fluorescence intensity, Electromyography, Nerve regeneration, Medicine

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Proceedings Article | 13 March 2024 Presentation

IDH targeted fluorescence guided surgery in low grade gliomas

Linton Evans, Lei Wang, Augustino Scorzo, Rendall Strawbridge, Scott Davis, Summer Gibbs

Proceedings Volume PC12825, PC128250S (2024) https://doi.org/10.1117/12.3023422

KEYWORDS: Fluorescence, Surgery, Tumors, Target designation, Resection, Molecules, Blood brain barrier, Toxicity, Proteins, In vitro testing

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Proceedings Article | 13 March 2024 Presentation

Quantitative fluorescence imaging of drug distribution and therapeutic response at single-cell resolution

Lei Wang, Antonio Montano, Nathan McMahon, Allison Solanki, Kimberley Samkoe, Kenneth Tichauer, Summer Gibbs

Proceedings Volume PC12821, PC128210D (2024) https://doi.org/10.1117/12.3003598

KEYWORDS: Tissues, Fluorophores, Fluorescence imaging, Therapeutics, Molecules, Biological imaging, Visualization, Live cell imaging, Fluorescence, Dyes

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Proceedings Article | 13 March 2024 Presentation

Development of near infrared contrast agents for non-invasive early-stage cancer detection

Grace Hubbell, Riley Whalen, Heather Theison, Joshua Pace, Junxiong Ma, Melissa Wong, Mark Niedre, Lei Wang, Summer Gibbs

Proceedings Volume PC12862, PC1286204 (2024) https://doi.org/10.1117/12.3003333

KEYWORDS: Cancer detection, Contrast agents, Near infrared, Cancer, Blood, Tumors, Oncology, Liquids, Flow cytometry, Diagnostics

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Proceedings Article | 13 March 2024 Presentation

Paired-agent imaging for measuring drug-target interactions in vivo

Kimberley Samkoe, Jonathan Elliott, Lei Wang, Summer Gibbs, Kenneth Tichauer

Proceedings Volume PC12821, PC1282102 (2024) https://doi.org/10.1117/12.3008552

KEYWORDS: In vivo imaging, Proteins, Therapeutics, Oncology, Molecules, Cell death, Animal model studies, Therapeutic agents, Solubility, Perfusion imaging

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Proceedings Article | 13 March 2024 Presentation

Prospects for fluorescence molecular in vivo liquid biopsy of circulating tumor cells

Joshua Pace, Madduri Srinivasarao, Shivakrishna Kallepu, Riley Whalen, Heather Theison, Grace Hubbell, Lei Wang, Melissa Wong, Summer Gibbs, Philip Low, Mark Niedre

Proceedings Volume PC12825, PC128250A (2024) https://doi.org/10.1117/12.3002790

KEYWORDS: In vivo imaging, Fluorescence, Cancer detection, Tumors, Liquids, Contrast agents, Biopsy, Blood, Near infrared, Cancer

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Proceedings Article | 13 March 2024 Presentation + Paper

Onward to better surgery - the critical need for improved ex vivo testing and training methods

Eric Henderson, Ryan Halter, Keith Paulsen, Brian Pogue, Jonathan Elliott, Ethan LaRochelle, Alberto Ruiz, Shudong Jiang, Samuel Streeter, Kimberley Samkoe, Summer Gibbs

Proceedings Volume 12825, 1282506 (2024) https://doi.org/10.1117/12.3010121

KEYWORDS: Surgery, Tissues, Animals, Animal model studies, Tumor growth modeling, Perfusion imaging, Optical properties, In vivo imaging, Diseases and disorders, Cancer

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SPIE Journal Paper | 13 May 2023 Open Access

Intraoperative molecular imaging: 3rd biennial clinical trials update

Patrick Bou-Samra, Najib Muhammad, Austin Chang, Ritesh Karsalia, Feredun Azari, Gregory Kennedy, Walter Stummer, Janos Tanyi, Linda Martin, Alexander Vahrmeijer, Barbara Smith, Eben Rosenthal, Patrick Wagner, David Rice, Amy Lee, Hafeez Abdelhafeez, Marcus M. Malek, Gary Kohanbash, Wilson Barry Edwards, Eric Henderson, Jane Skjøth-Rasmussen, Ryan Orosco, Summer Gibbs, Richard W. Farnam, Lalitha Shankar, Baran Sumer, Anand T. N. Kumar, Laura Marcu, Lei Li, Viktor Greuv, Edward J. Delikatny, John Y. K. Lee, Sunil Singhal

JBO, Vol. 28, Issue 05, 050901, (May 2023) https://doi.org/10.1117/12.10.1117/1.JBO.28.5.050901

KEYWORDS: Tumors, Surgery, Dyes, Clinical trials, Cancer, Resection, Fluorescence, Cancer detection, Near infrared, Tissues

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SPIE Journal Paper | 18 April 2023 Open Access

Dual probe difference specimen imaging for prostate cancer margin assessment

Marcus J. Kwon, Broderick J. House, Connor W. Barth, Allison Solanki, Jocelyn A. Jones, Scott C. Davis, Summer L. Gibbs

JBO, Vol. 28, Issue 08, 082806, (April 2023) https://doi.org/10.1117/12.10.1117/1.JBO.28.8.082806

KEYWORDS: Tumors, Adipose tissue, Prostate cancer, Prostate, Muscles, Tissues, Resection, Antibodies, Fluorescence, Cancer

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SignificancePositive margin status due to incomplete removal of tumor tissue during radical prostatectomy for high-risk localized prostate cancer requires reoperation or adjuvant therapy, which increases morbidity and mortality. Adverse effects of prostate cancer treatments commonly include erectile dysfunction, urinary incontinence, and bowel dysfunction, making successful initial curative prostatectomy imperative.AimCurrent intraoperative tumor margin assessment is largely limited to frozen section analysis, which is a lengthy, labor-intensive process that is obtrusive to the clinical workflow within the operating room (OR). Therefore, a rapid method for prostate cancer margin assessment in the OR could improve outcomes for patients.ApproachDual probe difference specimen imaging (DDSI), which uses paired antibody-based probes that are labeled with spectrally distinct fluorophores, was shown herein for prostate cancer margin assessment. The paired antibody-based probes consisted of a targeted probe to prostate-specific membrane antigen (PSMA) and an untargeted probe, which were used as a cocktail to stain resected murine tissue specimens including prostate tumor, adipose, muscle, and normal prostate. Ratiometric images (i.e., DDSI) of the difference between targeted and untargeted probe uptake were calculated and evaluated for accuracy using receiver operator characteristic curve analysis with area under the curve values used to evaluate the utility of the DDSI method to detect PSMA positive prostate cancer.ResultsTargeted and untargeted probe uptake was similar between the high and low PSMA expressing tumor due to nonspecific probe uptake after topical administration. The ratiometric DDSI approach showed substantial contrast difference between the PSMA positive tumors and their respective normal tissues (prostate, adipose, muscle). Furthermore, DDSI showed substantial contrast difference between the high PSMA expressing tumors and the minimally PSMA expressing tumors due to the ratiometric correction for the nonspecific uptake patterns in resected tissues.ConclusionsPrevious work has shown that ratiometic imaging has strong predictive value for breast cancer margin status using topical administration. Translation of the ratiometric DDSI methodology herein from breast to prostate cancers demonstrates it as a robust, ratiometric technique that provides a molecularly specific imaging modality for intraoperative margin detection. Using the validated DDSI protocol on resected prostate cancers permitted rapid and accurate assessment of PSMA status as a surrogate for prostate cancer margin status. Future studies will further evaluate the utility of this technology to quantitatively characterize prostate margin status using PSMA as a biomarker.

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Proceedings Article | 17 March 2023 Presentation

Quantitative fluorescence imaging of tyrosine kinase inhibitors in live cells and tissues (Conference Presentation)

Lei Wang, Antonio Montaño, Allison Solanki, Nathan McMahon, Kimberley Samkoe, Kenneth Tichauer, Summer Gibbs

Proceedings Volume PC12398, PC123980I (2023) https://doi.org/10.1117/12.2651093

KEYWORDS: Tissues, Luminescence, Live cell imaging, Molecules, Visualization, Therapeutics, Therapeutic agents, Rhodamine, Resistance, Receptors

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Proceedings Article | 17 March 2023 Presentation

Utilization of near infrared cranial nerve-specific fluorophores intraoperatively for visualization enhancement

Anas Masillati, Antonio Montaño, Lei Wang, Connor Barth, Dani Szafran-Reeder, Summer Gibbs

Proceedings Volume PC12361, PC123610L (2023) https://doi.org/10.1117/12.2650869

KEYWORDS: Visualization, Near infrared, Nerve, Lead, Tumors, Injuries, Tissues, Surgery, Skull, Sensors

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Proceedings Article | 17 March 2023 Presentation

Two-color imaging of vital nerve structures with applications in fluorescence-guided surgery using near-infrared fluorophores with improved physicochemical properties

Antonio Montaño, Anas Masillati, Lei Wang, Dani Szafran-Reeder, Connor Barth, Nourhan Shams, Summer Gibbs

Proceedings Volume PC12361, PC123610K (2023) https://doi.org/10.1117/12.2648521

KEYWORDS: Nerve, Surgery, Prostate cancer, Cancer, Tumors, Target designation, Proteins, Prostate, Near infrared, Lead

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Proceedings Article | 17 March 2023 Presentation

Clinical translation of near infrared nerve-specific fluorescence contrast agents for enhanced nerve identification during surgery

Connor Barth, Lei Wang, Antonio Montaño, Anas Masillati, Syed Rizvi, Adam Alani, Alexander Antaris, Jonathan Sorger, Summer Gibbs

Proceedings Volume PC12361, PC123610J (2023) https://doi.org/10.1117/12.2651327

KEYWORDS: Nerve, Surgery, Near infrared, Luminescence, Visualization, Tissues, Lead, Toxicology, Systems modeling, Safety

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Proceedings Article | 15 March 2023 Presentation + Paper

First demonstration of a novel nerve-targeting fluorophore in a cohort of ex vivo human tissues

Kendra Hebert, Logan Bateman, Dylan Parker, Jenna Nunziata, Joseph Paydarfar, Jennifer Hong, Darcy Kerr, George Zanazzi, Connor Barth, Lei Wang, Summer Gibbs, Eric Henderson

Proceedings Volume 12361, 123610D (2023) https://doi.org/10.1117/12.2650748

KEYWORDS: Fluorophores, Nervous system, Nerve, Adipose tissue, Lead, Biological samples, Surgery, Injuries, Muscles, Visualization

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Proceedings Article | 15 March 2023 Presentation + Paper

Proceduralist criteria for evaluating interface utility of novel imaging modalities in early phase clinical trials: evaluating the need for standardized criteria

Eric Henderson, Jonathan Elliott, Shudong Jiang, I. Leah Gitajn, John Lee, Summer Gibbs, Michael Bouvet, Anita Mahadevan-Jansen, Michael Daly, Samuel Streeter, Keith Paulsen, Brian Pogue, Kimberley Samkoe, Sunil Singhal

Proceedings Volume 12361, 123610F (2023) https://doi.org/10.1117/12.2650756

KEYWORDS: Surgery, Tissues, Target recognition, Standards development, Visualization, Medical imaging, Imaging technologies, Clinical trials, Interfaces, Fluorophores

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Proceedings Article | 15 March 2023 Presentation + Paper

Use of freshly amputated human limbs for pre-clinical evaluation of molecular-targeted fluorescent probes

Logan Bateman, Kendra Hebert, Samuel Streeter, Jenna Nunziata, Connor Barth, Lei Wang, Summer Gibbs, Eric Henderson

Proceedings Volume 12361, 1236109 (2023) https://doi.org/10.1117/12.2650356

KEYWORDS: Fluorophores, Animal model studies, Tissues, Nervous system, Nerve, Animals, Lead, Surgery, Performance modeling, Muscles

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SPIE Journal Paper | 5 January 2023 Open Access

Preclinical evaluation of molecularly targeted fluorescent probes in perfused amputated human limbs

Logan Bateman, Kendra Hebert, Jenna Nunziata, Samuel Streeter, Connor Barth, Lei Wang, Summer Gibbs, Eric Henderson

JBO, Vol. 28, Issue 08, 082802, (January 2023) https://doi.org/10.1117/12.10.1117/1.JBO.28.8.082802

KEYWORDS: Fluorophores, Nerve, Nervous system, Animal model studies, Lead, Adipose tissue, Tissues, Imaging systems, Muscles, Fluorescence imaging

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Proceedings Article | 7 March 2022 Presentation

Utilization of near infrared nerve-specific fluorescent contrast agents as an intraoperative assessment methodology for nerve damage

Anas Masillati, Summer Gibbs, Connor Barth, Lei Wang, Nourhan Shams, Antonio Montano

Proceedings Volume PC11943, PC119430C (2022) https://doi.org/10.1117/12.2626009

KEYWORDS: Nerve, Near infrared, Injuries, Tissues, Surgery, Visualization, Molecules, Lead

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Proceedings Article | 4 March 2022 Presentation + Paper

The advantages and disadvantages of novel contrast agent types for fluorescence guided surgery

Connor Barth, Summer Gibbs

Proceedings Volume 11943, 1194309 (2022) https://doi.org/10.1117/12.2613182

KEYWORDS: Drug development, Nano contrast agents, Fluorescent markers, Image-guided intervention, Fluorescent materials, Molecules, Safety, Proteins, Clinical trials, Surgery, Nanoparticles, Tissues, Toxicity, Toxicology

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Proceedings Article | 4 March 2022 Presentation + Paper

An investigation into the in vivo performance of Changsha and rhodamine fluorophores

Antonio Montaño, Lei Wang, Anas Masillati, Nourhan Shams, Summer Gibbs

Proceedings Volume 11943, 119430A (2022) https://doi.org/10.1117/12.2626051

KEYWORDS: Nerve, Rhodamine, Rhodamine B, Near infrared, Absorbance, Injuries, In vivo imaging, Surgery

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Proceedings Article | 4 March 2022 Presentation + Paper

Fine-tuning physicochemical properties of Oxazine-4 for nerve-specific imaging

William Greer, Antonio Montaño, Nourhan Shams, Dani Szafran-Reeder, Anas Masillati, Lei Wang, Summer Gibbs

Proceedings Volume 11943, 1194308 (2022) https://doi.org/10.1117/12.2612232

KEYWORDS: Nerve, Tissues, In vivo imaging, Visualization

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Proceedings Article | 4 March 2022 Presentation

Quantitative imaging of tyrosine kinase inhibitor distribution in live cells and tissues

Lei Wang, Antonio Montaño, Allison Solanki, Nathan McMahon, Kenneth Tichauer, Kimberley Samkoe, Summer Gibbs

Proceedings Volume PC11979, PC119790I (2022) https://doi.org/10.1117/12.2612233

KEYWORDS: Tissues, Live cell imaging, Molecules, Luminescence, Cancer, Visualization, Resistance, Therapeutics, Therapeutic agents, Rhodamine

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Proceedings Article | 4 March 2022 Presentation + Paper

Nonlinear unmixing to account for blood absorption in multispectral imaging for improved quantification of intracellular and extracellular EGFR

Veronica Torres, Lei Wang, Sassan Hodge, Allison Solanki, Nathan McMahon, Summer Gibbs, Kenneth Tichauer, Kimberley Samkoe

Proceedings Volume 11938, 1193805 (2022) https://doi.org/10.1117/12.2609773

KEYWORDS: Tumors, Blood, Content addressable memory, Absorption, Multispectral imaging, Luminescence, Tumor growth modeling, Receptors, Proteins, Therapeutics

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SPIE Journal Paper | 17 May 2021 Open Access

Intraoperative molecular imaging clinical trials: a review of 2020 conference proceedings

Feredun Azari, Gregory Kennedy, Elizabeth Bernstein, Constantinos Hadjipanayis, Alexander Vahrmeijer, Barbara Smith, Eben Rosenthal, Baran Sumer, Jie Tian, Eric Henderson, Amy Lee, Quyen Nguyen, Summer Gibbs, Brian Pogue, Daniel Orringer, Cleopatra Charalampaki, Linda Martin, Janos Tanyi, Major Lee, John Y. Lee, Sunil Singhal

JBO, Vol. 26, Issue 05, 050901, (May 2021) https://doi.org/10.1117/12.10.1117/1.JBO.26.5.050901

KEYWORDS: Tumors, Surgery, Cancer, Tissues, Clinical trials, Imaging systems, Luminescence, Molecular imaging, Medicine, Near infrared

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Significance: Surgery is often paramount in the management of many solid organ malignancies because optimal resection is a major factor in disease-specific survival. Cancer surgery has multiple challenges including localizing small lesions, ensuring negative surgical margins around a tumor, adequately staging patients by discriminating positive lymph nodes, and identifying potential synchronous cancers. Intraoperative molecular imaging (IMI) is an emerging potential tool proposed to address these issues. IMI is the process of injecting patients with fluorescent-targeted contrast agents that highlight cancer cells prior to surgery. Over the last 5 to 7 years, enormous progress has been achieved in tracer development, near-infrared camera approvals, and clinical trials. Therefore, a second biennial conference was organized at the University of Pennsylvania to gather surgical oncologists, scientists, and experts to discuss new investigative findings in the field. Our review summarizes the discussions from the conference and highlights findings in various clinical and scientific trials. Aim: Recent advances in IMI were presented, and the importance of each clinical trial for surgical oncology was critically assessed. A major focus was to elaborate on the clinical endpoints that were being utilized in IMI trials to advance the respective surgical subspecialties. Approach: Principal investigators presenting at the Perelman School of Medicine Abramson Cancer Center’s second clinical trials update on IMI were selected to discuss their clinical trials and endpoints. Results: Multiple phase III, II, and I trials were discussed during the conference. Since the approval of 5-ALA for commercial use in neurosurgical malignancies, multiple tracers and devices have been developed to address common challenges faced by cancer surgeons across numerous specialties. Discussants also presented tracers that are being developed for delineation of normal anatomic structures that can serve as an adjunct during surgical procedures. Conclusions: IMI is increasingly being recognized as an improvement to standard oncologic surgical resections and will likely advance the art of cancer surgery in the coming years. The endpoints in each individual surgical subspecialty are varied depending on how IMI helps each specialty solve their clinical challenges.

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Proceedings Article | 8 March 2021 Presentation

Development of near-infrared fluorophores for use as nerve-specific contrast agents for fluorescence guided surgery

Lei Wang, Connor Barth, Antonio Montaño, Alexander Antaris, Jonathan Sorger, Summer Gibbs

Proceedings Volume 11625, 116250S (2021) https://doi.org/10.1117/12.2583286

KEYWORDS: Nerve, Luminescence, Tissues, Near infrared, Imaging systems, Visualization, Safety, Real time imaging, Molecules, Surgery

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Proceedings Article | 7 March 2021 Presentation

Water-soluble and cell-permeant zwitterionic rhodamine dyes enable quantitative imaging of drug target engagement

Antonio Montaño, Lei Wang, Allison Solanki, Nathan McMahon, Marcus Kwon, Kenneth Tichauer, Kimberley Samkoe, Summer Gibbs

Proceedings Volume 11624, 116240H (2021) https://doi.org/10.1117/12.2582638

KEYWORDS: Rhodamine, Cancer, Resistance, Molecules, Imaging systems, Visualization, Silicon, Receptors, Oncology, Dynamical systems

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Proceedings Article | 7 March 2021 Open Access

Near-infrared nerve-specific probes to guide surgery

Summer Gibbs

Proceedings Volume 11625, 1162503 (2021) https://doi.org/10.1117/12.2596408

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Proceedings Article | 5 March 2021 Presentation + Paper

A method for validating depth-resolved biodistributions in topically-stained specimen with multi-channel fluorescence cryo-imaging

Brook Byrd, Rendall Strawbridge, Wendy Wells, Connor Barth, Summer Gibbs, Scott Davis

Proceedings Volume 11625, 116250X (2021) https://doi.org/10.1117/12.2582542

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Proceedings Article | 5 March 2021 Presentation

TRIPODD: a novel fluorescence imaging platform for in situ measurement of drug distribution and proteomic therapeutic response

Nathan McMahon, Allison Solanki, Lei Wang, Jocelyn Jones, Kimberly Samkoe, Kenneth Tichauer, Summer Gibbs

Proceedings Volume 11624, 116240L (2021) https://doi.org/10.1117/12.2582773

KEYWORDS: Proteins, Luminescence, In situ metrology, Tumors, Tissues, Therapeutics, Spatial resolution, Resistance, Receptors, Medicine

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Proceedings Article | 5 March 2021 Presentation

Pharmacology of near infrared nerve-specific fluorophores for fluorescence-guided nerve sparing surgical procedures

Connor Barth, Lei Wang, Antonio Montaño, Alexander Antaris, Jonathan Sorger, Summer Gibbs

Proceedings Volume 11625, 116250R (2021) https://doi.org/10.1117/12.2583265

KEYWORDS: Nerve, Near infrared, Pharmacology, Visualization, Toxicity, Safety, Animal model studies, Surgery, Luminescence, Imaging systems

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SPIE Journal Paper | 22 May 2020 Open Access

Oligonucleotide conjugated antibodies permit highly multiplexed immunofluorescence for future use in clinical histopathology

Nathan McMahon, Jocelyn A. Jones, Sunjong Kwon, Koei Chin, Michel Nederlof, Joe Gray, Summer Gibbs

JBO, Vol. 25, Issue 05, 056004, (May 2020) https://doi.org/10.1117/12.10.1117/1.JBO.25.5.056004

KEYWORDS: Tissues, Multiplexing, Breast cancer, Luminescence, Visualization, Ultraviolet radiation, Breast, Cancer, Tumors, Proteins

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Proceedings Article | 20 April 2020 Presentation

Quantification of tissue distribution and therapeutic response using paired agent imaging in a chicken chorioallantoic membrane xenograft assay (Conference Presentation)

Kimberley Samkoe, Lei Wang, Jesse Korber, Summer Gibbs, Kenneth Tichauer

Proceedings Volume 11219, 112190E (2020) https://doi.org/10.1117/12.2547100

KEYWORDS: Tumors, Tissues, 3D modeling, Content addressable memory, In vivo imaging, Molecules, Statistical modeling

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Proceedings Article | 19 February 2020 Paper

Noninvasive in vivo mapping of intracellular signaling proteins using a pairing of targeted and untargeted fluorescently labeled small molecule kinase inhibitors

Kenneth Tichauer, Lei Wang, Allison Solanki, Jesse Korber, Summer Gibbs, Kimberley Samkoe

Proceedings Volume 11219, 112190K (2020) https://doi.org/10.1117/12.2545926

KEYWORDS: Information technology, Tissues, Molecules, In vivo imaging, Mathematical modeling, Imaging systems, Proteins, Cancer, Plasma, Differential equations

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Proceedings Article | 19 February 2020 Paper

In vivo nerve-specificity of rhodamines and Si-rhodamines

Antonio Montaño, Lei Wang, Connor Barth, Nourhan Shams, K. A. Sashini Kumarapeli, Summer Gibbs

Proceedings Volume 11222, 112220I (2020) https://doi.org/10.1117/12.2545311

KEYWORDS: Rhodamine, Nerve, Near infrared, In vivo imaging, Surgery

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Proceedings Article | 19 February 2020 Presentation + Paper

Fluorescence image-guided surgery: a perspective on contrast agent development

Connor Barth, Summer Gibbs

Proceedings Volume 11222, 112220J (2020) https://doi.org/10.1117/12.2545292

KEYWORDS: Imaging systems, Luminescence, Surgery, Cancer, Multichannel imaging systems, Clinical trials, Tumors, Near infrared, Colorectal cancer, Pancreatic cancer, Image-guided intervention

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Proceedings Article | 19 February 2020 Paper

Fluorescent imaging technologies for in situ measurement of drug target engagement and cell signaling pathways

Nathan McMahon, Allison Solanki, Jocelyn Jones, Sunjong Kwon, Young-Hwan Chang, Koei Chin, Michel Nederlof, Joe Gray, Summer Gibbs

Proceedings Volume 11219, 112190O (2020) https://doi.org/10.1117/12.2546320

KEYWORDS: Tissues, Tumors, Resistance, Cancer, Proteins, Imaging spectroscopy, Visualization, Oncology, Multiplexing

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Successful cancer treatment continues to elude modern medicine and its arsenal of therapeutic strategies. Therapy resistance is driven by significant tumor heterogeneity, complex interactions between malignant, microenvironmental and immune cells and cross talk between signaling pathways. Advances in molecular characterization technologies such as next generation sequencing have helped unravel this network of interactions and identify druggable therapeutic targets. Tyrosine kinase inhibitors (TKI) are a class of drugs seeking to inhibit signaling pathways critical to sustaining proliferative signaling, resisting cell death, and the other hallmarks of cancer. While tumors may initially respond to TKI therapy, disease progression is near universal due to mechanisms of acquired resistance largely involving cellular signaling pathway reprogramming. With the ultimate goal of improved TKI therapeutic efficacy our group has developed intracellular paired agent imaging (iPAI) to quantify drug target interactions and oligonucleotide conjugated antibody (Ab-oligo) cyclic immunofluorescence (cycIF) imaging to characterize perturbed signaling pathways in response to therapy. iPAI uses spectrally distinct, fluorescently labeled targeted and untargeted drug derivatives, correcting for non-specific drug distribution and facilitating quantitative assessment of the drug binding before and after therapy. Ab-oligo cycIF exploits in situ hybridization of complementary oligonucleotides for biomarker labeling while oligonucleotide modifications facilitate signal removal for sequential rounds of fluorescent tagging and imaging. Aboligo CycIF is capable of generating extreme multi-parametric images for quantifying total and phosphorylated protein expression to quantify protein activation, expression, and spatial distribution. Together iPAI and Ab-oligo cycIF can be applied to interrogate drug uptake and target binding as well as changes to heterogenous cell populations within tumors that drive variable therapeutic responses in patients.

Proceedings Article | 19 February 2020 Presentation + Paper

Intracellular paired agent imaging enables improved evaluation of tyrosine kinase inhibitor target engagement

Allison Solanki, Lei Wang, Jesse Korber, Nathan McMahon, Kenneth Tichauer, Kimberley Samkoe, Summer Gibbs

Proceedings Volume 11219, 112190F (2020) https://doi.org/10.1117/12.2546234

KEYWORDS: Tumors, Tissues, Proteins, Imaging systems, In vivo imaging, Cancer, Visualization, Receptors

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Targeting the aberrant epidermal growth factor receptor (EGFR) signaling pathway is an attractive choice for many cancers (e.g., non-small cell lung carcinoma (NSCLC) and head and neck squamous cell carcinoma (HNSCC)). Despite the development of promising therapeutics, incomplete target engagement and acquired resistance (e.g., mutagenesis and intracellular signaling pathway rewiring) ensure that curative options still elude patients. To address limitations posed by standard drug evaluation assays (e.g., western blot, bulk plasma monitoring, immunohistochemistry), we have developed a novel dynamic, fluorescence-based platform termed intracellular paired agent imaging (iPAI). iPAI quantifies intracellular protein target engagement using two matched small-molecule, cell membrane-permeable agents: one targeted to the protein of interest and one untargeted, which accounts for non-specific therapeutic uptake. Currently, our iPAI panel includes successfully characterized tyrosine kinase inhibitors targeting the kinase binding domain of numerous proteins in the EGFR pathway, including erlotinib (EGFR). Here, we present a pharmacokinetic uptake study using our novel iPAI erlotinib reagents: a targeted erlotinib probed conjugated to silicon tetramethylrhodamine (Erl- SiTMR-T) and an untargeted reagent conjugated to tetramethylrhodaime (Erl-TMR-UT). An initial uptake study in a cell derived xenograft (CDX) model of NSCLC was performed by administering the Erl iPAI reagents systemically via tail vein injection, where drug uptake was quantified in the tumor over time. Excitingly, evidence of heterogeneous uptake was observed in the iPAI injected cohort, displaying distinct drug-uptake within a single tumor. Characterization of additional iPAI agents targeting downstream effectors (e.g., AKT, PI3K, MEK and ERK) is ongoing and will allow us to visualize complex drug-target interactions and quantify their downstream signaling partners during treatment regimens for NSCLC and other cancers. Together, we anticipate these iPAI probes will improve understanding of current limitations in personalized cancer therapy.

Proceedings Article | 7 March 2019 Paper

Effect of staining temperature on topical dual stain imaging of tissue specimens for tumor identification

Margaret Folaron, Rendall Strawbridge, Kimberley Samkoe, Summer Gibbs, Scott Davis

Proceedings Volume 10862, 108620L (2019) https://doi.org/10.1117/12.2509848

KEYWORDS: Tissues, Tumors, Surgery, Diagnostics, Receptors, Imaging systems

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Proceedings Article | 7 March 2019 Paper

Diagnostic performance of receptor-specific surgical specimen staining correlate with receptor expression level

Broderick House, Jasmin Schaefer, Connor Barth, Scott Davis, Summer Gibbs

Proceedings Volume 10862, 108620K (2019) https://doi.org/10.1117/12.2510625

KEYWORDS: Tumors, Tissues, Surgery, Cancer, Diagnostics, Breast, Receptors, Breast cancer, Luminescence

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Identification of tumor margins in the operating room in real time is a critical challenge for surgical procedures that serve as cancer cure. Breast conserving surgery (BCS) is particularly affected by this problem, with current reexcision rates above 25%. Due to a lack of clinically available methodologies for detection of involved or close tumor margins, much effort is focused on developing intraoperative margin assessment modalities that can aid in addressing this unmet clinical need. BCS provides a unique opportunity to design contrast-based technologies that are able to assess tumor margins independent from the patient, providing a rapid pathway from bench to bedside at a much lower cost. Since resected tissue is removed from the patient’s blood supply, non-specific contrast agent uptake becomes a challenge due to the lack of clearance. Therefore, a dual probe, ratiometric fluorescence imaging approach was taken in an effort to reduce non-specific signal, and provide a modality that could demonstrate rapid, robust margin assessment on resected patient samples. Termed, dual-stain difference specimen imaging (DDSI), DDSI includes the use of spectrally unique, and fluorescently labeled target-specific, as well as non-specific biomarkers. In the present study, we have applied epidermal growth factor receptor (EGFR) targeted DDSI to tumor xenografts with variable EGFR expression levels using a previously optimized staining protocol, allowing for a quantitative assessment of the predictive power of the technique under biologically relevant conditions. Due to the presence of necrosis in the model tumors, ring analysis was employed to characterize diagnostic accuracy as measured by receiver operator characteristic (ROC) curve analysis. Our findings demonstrate the robust nature of the DDSI technique even in the presence of variable biomarker expression and spatial patterns. These results support the continued development of this technology as a robust diagnostic tool for tumor margin assessment in resected specimens during BCS.

Proceedings Article | 7 March 2019 Presentation + Paper

Fluorescent nerve identification in resected human tissue specimens

Connor Barth, Christopher Amling, Summer Gibbs

Proceedings Volume 10862, 108620R (2019) https://doi.org/10.1117/12.2510512

KEYWORDS: Nerve, Tissues, Prostate, Luminescence, Imaging systems, Surgery, Image-guided intervention, Robotics, Blood, Biomedical optics and medical imaging, Medical imaging, Medical imaging applications, Molecular imaging, Optical imaging

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Proceedings Article | 7 March 2019 Paper

Investigation of oxazine and rhodamine derivatives as peripheral nerve tissue targeting contrast agent for in vivo fluorescence imaging

Lei Wang, Connor Barth, Jason Combs, Antonio Montaño, Summer Gibbs

Proceedings Volume 10862, 108620H (2019) https://doi.org/10.1117/12.2507296

KEYWORDS: Rhodamine, Nerve, Tissues, In vivo imaging, Absorbance, Near infrared, Image-guided intervention

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Proceedings Article | 4 March 2019 Presentation + Paper

Signal removal methods for highly multiplexed immunofluorescent staining using antibody conjugated oligonucleotides

Nathan McMahon, Jocelyn Jones, Jennifer Eng, Sunjong Kwon, Young-Hwan Chang, Guillaume Thibault, Koei Chin, Michel Nederlof, Joe Gray, Summer Gibbs

Proceedings Volume 10881, 108810X (2019) https://doi.org/10.1117/12.2510573

KEYWORDS: Tissues, Multiplexing, Luminescence, Ultraviolet radiation, Cancer, Tumors, Tissue optics, Genomics, Bioalcohols, Microscopes

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Proceedings Article | 28 February 2019 Paper

Simultaneous extracellular and intracellular quantification of EGFR using paired-agent imaging in an in ovo tumor model

Kimberley Samkoe, Emily Schultz, Allison Solanki, Lei Wang, Jesse Korber, Kenneth Tichauer, Summer Gibbs

Proceedings Volume 10859, 108590F (2019) https://doi.org/10.1117/12.2510778

KEYWORDS: Tumors, Content addressable memory, Luminescence, Proteins, Molecules, Tissues, Multispectral imaging, Receptors, Control systems, Tumor growth modeling

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SPIE Journal Paper | 8 February 2019 Open Access

Diagnostic performance of receptor-specific surgical specimen staining correlates with receptor expression level

Jasmin Schaefer, Connor Barth, Scott Davis, Summer Gibbs

JBO, Vol. 24, Issue 02, 026002, (February 2019) https://doi.org/10.1117/12.10.1117/1.JBO.24.2.026002

KEYWORDS: Tumors, Tissues, Diagnostics, Receptors, Luminescence, Surgery, Biological research, Cancer, Flow cytometry, Statistical analysis

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SPIE Journal Paper | 6 July 2018 Open Access

Nile Red derivatives enable improved ratiometric imaging for nerve-specific contrast

Jesse Korber, Connor Barth, Summer Gibbs

JBO, Vol. 23, Issue 07, 076002, (July 2018) https://doi.org/10.1117/12.10.1117/1.JBO.23.7.076002

KEYWORDS: Tissues, Nerve, Luminescence, Magnesium, In vivo imaging, Nitrogen, Quantum efficiency, Surgery, Molecules, Chromatography

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Proceedings Article | 14 March 2018 Presentation

Paired agent imaging enables rapid assessment of therapeutic efficacy for personalized therapy (Conference Presentation)

Emily Schultz, Allison Solanki, Lei Wang, Kenneth Tichauer, Summer Gibbs

Proceedings Volume 10475, 104750K (2018) https://doi.org/10.1117/12.2290626

KEYWORDS: Resistance, Cancer, Medicine, Pancreatic cancer, Surgery, Visualization, Oncology, Biopsy

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Proceedings Article | 14 March 2018 Presentation

Topical application of nerve-specific fluorophores for image-guided nerve sparing surgical procedures (Conference Presentation)

Connor Barth, Summer Gibbs, Lei Wang

Proceedings Volume 10478, 104780J (2018) https://doi.org/10.1117/12.2290681

KEYWORDS: Nerve, Luminescence, Image-guided intervention, Surgery, Visualization, Tissues, Near infrared, Oncology, Target designation, Molecular imaging

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Nerve damage plagues surgical outcomes, significantly affecting post-surgical quality of life. Surprisingly, no method exists to enhance direct nerve visualization in the operating room, and nerve detection is completed through a combination of palpation and visualization when possible. Fluorescence image-guided surgery offers a potential means of enhanced nerve identification and preservation, however a clinically approved nerve-specific contrast agent does not yet exist. Several classes of nerve-specific fluorophores have recently been demonstrated including the distyrylbenzenes (DSB), select oxazines (oxazine 4 perchlorate), and certain cyanines (3,3’-diethylthiatricarbocyanine iodine), which could provide intraoperative guidance. The nerve-sparing radical prostatectomy is a surgical procedure that could benefit from fluorescence image-guided nerve identification. Although the nerve-sparing surgical technique was developed over 30 years ago, nerve damage following radical prostatectomy is reported in some form in up to 60% of patients one to two years post-surgery. To facilitate clinical translation of fluorescence image guided surgery to the nerve sparing prostatectomy, a direct administration methodology was developed that allows selective nerve highlighting with a significantly lower fluorophore dose than systemic administration, where large animal studies have confirmed the technique’s translatability. Tissue penetration will be critical for clinical feasibility of the direct administration methodology and novel formulation strategies have been explored to enhance tissue penetration for identifying buried nerves. In addition, several biomolecular targets of Oxazine 4, a promising candidate for nerve-specific fluorophore development into a near-infrared (NIR) agent, have been identified, providing insight into the mechanism of nerve-specificity. Fluorophore development has made progress towards the goal of creating a NIR nerve-specific fluorophore and determining the structure-activity relationship responsible for nerve binding.

Proceedings Article | 14 March 2018 Presentation

Quantitative imaging of gemcitabine engagement and efficacy in pancreatic cancer (Conference Presentation)

Lei Wang, Allison Solanki, Kenneth Tichauer, Summer Gibbs

Proceedings Volume 10475, 104750L (2018) https://doi.org/10.1117/12.2291265

KEYWORDS: Therapeutics, Pancreatic cancer, Luminescence, Cancer, Liquids, Chromatography, Mass spectrometry

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Proceedings Article | 14 March 2018 Presentation

Dual probe difference specimen imaging for rapid identification of margin assessment during breast conserving surgery (Conference Presentation)

Jasmin Schaefer, Connor Barth, Vince Rossi, Kimberley Samkoe, Scott Davis, Summer Gibbs

Proceedings Volume 10478, 104780M (2018) https://doi.org/10.1117/12.2290677

KEYWORDS: Surgery, Breast cancer, Tumors, Luminescence, Breast, Image-guided intervention, Molecules, Tissues

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Proceedings Article | 19 April 2017 Presentation

Quantitative imaging of intracellular signaling for personalized pancreatic cancer therapy in an in vivo avatar (Conference Presentation)

Kimberley Samkoe, Emily Schultz, Yeonjae Park, Dawn Fischer, Brian Pogue, Kerrington Smith, Kenneth Tichauer, Summer Gibbs

Proceedings Volume 10046, 100460B (2017) https://doi.org/10.1117/12.2254052

KEYWORDS: Tumors, Medicine, Proteins, Imaging systems, Tissues, Receptors, Pancreatic cancer, Genetics, Flow cytometry, In vivo imaging

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Proceedings Article | 27 April 2016 Presentation

Screening photoswitching properties of synthesized BODIPY-based fluorophores for multispectral superresolution microscopy (MSSRM) (Conference Presentation)

Amy Bittel, Isaac Saldivar, Xiaolin Nan, Summer Gibbs

Proceedings Volume 9714, 97140S (2016) https://doi.org/10.1117/12.2213462

KEYWORDS: Microscopy, Super resolution, Spectral resolution, Visible radiation, Quantum efficiency, Molecules, Proteins, Oxygen, Imaging spectroscopy, Single molecule spectroscopy

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Proceedings Article | 4 March 2016 Presentation + Paper

Visualizing Oxazine 4 nerve-specific fluorescence ex vivo in frozen tissue sections

Connor Barth, Summer Gibbs

Proceedings Volume 9696, 96960R (2016) https://doi.org/10.1117/12.2214204

KEYWORDS: Nerve, Visualization, Luminescence, Tissues, Visual analytics, Image-guided intervention, Near infrared, Prostate cancer, Molecules, Surgery, In vivo imaging, Microscopy, Optical filters

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Proceedings Article | 9 March 2015 Paper

Effect of labeling density and time post labeling on quality of antibody-based super resolution microscopy images

Amy Bittel, Isaac Saldivar, Nicholas Dolman, Andrew Nickerson, Li-Jung Lin, Xiaolin Nan, Summer Gibbs

Proceedings Volume 9331, 93310M (2015) https://doi.org/10.1117/12.2083209

KEYWORDS: Proteins, Image quality, Signal detection, Molecules, Luminescence, Microscopy, Super resolution microscopy, Spatial resolution, Video, Image resolution

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Proceedings Article | 4 March 2014 Paper

Design and development of BODIPY-based photoswitchable fluorophores to visualize cell signaling with multispectral super resolution microscopy

Amy Bittel, Andrew Nickerson, Li-Jung Lin, Xiaolin Nan, Summer Gibbs

Proceedings Volume 8950, 89500S (2014) https://doi.org/10.1117/12.2040498

KEYWORDS: Molecules, Switching, Picture Archiving and Communication System, Photons, Super resolution microscopy, Signal detection, Particles, Microscopy, Luminescence, Solids

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SPIE Journal Paper | 1 September 2011 Open Access

Protoporphyrin IX fluorescence contrast in invasive glioblastomas is linearly correlated with Gd enhanced magnetic resonance image contrast but has higher diagnostic accuracy

Kimberley Samkoe, Summer Gibbs-Strauss, Harold Yang, Paul Hoopes, Julia O'Hara, Brian Pogue, S. Khan Hekmatyar, Risto Kauppinen

JBO, Vol. 16, Issue 09, 096008, (September 2011) https://doi.org/10.1117/12.10.1117/1.3622754

KEYWORDS: Luminescence, Tumors, Green fluorescent protein, Magnetic resonance imaging, Gadolinium, Tissues, Image enhancement, Brain, Control systems, Diagnostics

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Proceedings Article | 10 February 2011 Paper

Image contrast in fluorescence and magnetic resonance images for glioblastoma detection

Kimberley Samkoe, Summer Gibbs-Strauss, Harold Yang, S. Khan Hekmatyar, P. Jack Hoopes, Julia O'Hara, Risto Kauppinen, Brian Pogue

Proceedings Volume 7892, 78920O (2011) https://doi.org/10.1117/12.875425

KEYWORDS: Luminescence, Magnetic resonance imaging, Tumors, Diffusion, Green fluorescent protein, Brain, Gadolinium, Magnetism, Imaging systems, Image enhancement

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SPIE Journal Paper | 1 September 2010 Open Access

Comparing implementations of magnetic-resonance-guided fluorescence molecular tomography for diagnostic classification of brain tumors

Scott Davis, Kimberley Samkoe, Julia O'Hara, Summer Gibbs-Strauss, Keith Paulsen, Brian Pogue

JBO, Vol. 15, Issue 05, 051602, (September 2010) https://doi.org/10.1117/12.10.1117/1.3483902

KEYWORDS: Tumors, Luminescence, Brain, Tissues, Magnetic resonance imaging, Image segmentation, Tissue optics, Diagnostics, Spectroscopy, Image restoration

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SPIE Journal Paper | 1 May 2009 Open Access

Imaging of glioma tumor with endogenous fluorescence tomography

Dax Kepshire, Summer Gibbs-Strauss, Julia O'Hara, Michael Hutchins, Niculae Mincu, Frederic Leblond, Mario Khayat, Hamid Dehghani, Subhadra Srinivasan, Brian Pogue

JBO, Vol. 14, Issue 03, 030501, (May 2009) https://doi.org/10.1117/12.10.1117/1.3127202

KEYWORDS: Tumors, Luminescence, Fluorescence tomography, Tomography, Imaging systems, Signal detection, Tissues, Calibration, Fluorescence spectroscopy, Single photon detectors

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SPIE Journal Paper | 1 May 2009 Open Access

Errata: Imaging of glioma tumor with endogenous fluorescence tomography

Dax Kepshire, Summer Gibbs-Strauss, Julia O'Hara, Frederic Leblond, Subhadra Srinivasan, Brian Pogue, Michael Hutchins, Niculae Mincu, Mario Khayat, Hamid Dehghani

JBO, Vol. 14, Issue 03, 039802, (May 2009) https://doi.org/10.1117/12.10.1117/1.3157198

KEYWORDS: Tumors, Fluorescence tomography, Medical research, Physics, Roads, Diagnostics, Radiology

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SPIE Journal Paper | 1 January 2009 Open Access

Noninvasive measurement of aminolevulinic acid-induced protoporphyrin IX fluorescence allowing detection of murine glioma in vivo

Summer Gibbs-Strauss, Julia O'Hara, P. Jack Hoopes, Tayyaba Hasan, Brian Pogue

JBO, Vol. 14, Issue 01, 014007, (January 2009) https://doi.org/10.1117/12.10.1117/1.3065543

KEYWORDS: Tumors, Luminescence, Tissues, Brain, Spectroscopy, Fluorescence spectroscopy, In vivo imaging, Skin, Magnetic resonance imaging, Green fluorescent protein

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Proceedings Article | 7 March 2008 Paper

MRI-coupled spectrally resolved fluorescence tomography for in vivo imaging

Scott Davis, Summer Gibbs-Strauss, Stephen Tuttle, Shudong Jiang, Roger Springett, Hamid Dehghani, Brian Pogue, Keith Paulsen

Proceedings Volume 6850, 68500K (2008) https://doi.org/10.1117/12.764252

KEYWORDS: Luminescence, Magnetic resonance imaging, Imaging systems, Optical fibers, Optical filters, Fluorescence tomography, Spectrometers, Calibration, Image segmentation, Tissue optics

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Proceedings Article | 25 February 2008 Paper

Noninvasive murine glioma detection improved following photobleaching of skin PpIX fluorescence

Summer Gibbs-Strauss, Scott Davis, Julia O'Hara, P. Jack Hoopes, Tayyaba Hasan, Brian Pogue

Proceedings Volume 6845, 68450D (2008) https://doi.org/10.1117/12.762997

KEYWORDS: Luminescence, Skin, Tumors, Brain, Spectroscopy, Imaging systems, Photodynamic therapy, Tissues, Visualization, Tissue optics

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Proceedings Article | 27 February 2007 Paper

Improved murine glioma detection following modified diet and photobleaching of skin PpIX fluorescence

Summer Gibbs, Julia O'Hara, P. Jack Hoopes, Brian Pogue

Proceedings Volume 6427, 64270D (2007) https://doi.org/10.1117/12.700456

KEYWORDS: Luminescence, Skin, Tumors, Tissues, Brain, Spectroscopy, Head, Imaging systems, Fluorescence spectroscopy, Tissue optics

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Proceedings Article | 6 March 2006 Paper

Comparison of techniques for quantification of fluorescence from tissue

Brian Pogue, Xiaodong Zhou, Summer Gibbs, Scott Davis, Dax Kepshire, Keith Paulsen, Tayyaba Hasan

Proceedings Volume 6139, 61390N (2006) https://doi.org/10.1117/12.647572

KEYWORDS: Luminescence, Tissues, In vivo imaging, Tissue optics, Tumors, Imaging systems, Tomography, Raster graphics, Scattering, Confocal microscopy

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Proceedings Article | 6 March 2006 Paper

Analysis of cell line variation in biochemical production of protoporphyrin IX

Summer Gibbs, Bin Chen, Julia O'Hara, P. Jack Hoopes, Tayyaba Hasan, Brian Pogue

Proceedings Volume 6139, 61390A (2006) https://doi.org/10.1117/12.644787

KEYWORDS: Luminescence, Iron, Lithium, Flow cytometry, Cancer, Photodynamic therapy, Statistical analysis, Tissues, Prostate, Scatter measurement

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Protoporphyrin IX (PpIX) is produced via the heme synthesis pathway by the cell following administration of aminolevulinic acid (ALA). ALA synthase, the enzyme that produces ALA in the cell from glycine and succinyl-coenzyme A, is inhibited in a feedback mechanism by heme and thus is the rate limiting enzyme in the heme synthesis pathway. Since ALA is administered systemically, the rate limiting step that naturally exists in the cells is bypassed, however it is currently unclear why cells have different rate limiting steps in the ALA-PpIX synthesis pathway, and more specifically which types of cancer cells are most productive. It has been determined that when the same amount of ALA is administered to a wide panel of cancer cells in vitro that vastly differing amounts of PpIX are produced. The steps for the ALA-PpIX pathway occur in and around the mitochondria of the cell, but interestingly no correlation is seen between PpIX production and mitochondrial content of the cell, following ALA administration. However, total cell area shows positive correlation with PpIX production. Administration of the iron chelator, 1,2-dimethyl-3-hydroxy-4-pyridone (L1) in combination with ALA allows the final step in the heme synthesis pathway, conversion of PpIX to heme, to be delayed and thus increases the detectable amount of PpIX in each cell line. The cell lines that have the lowest PpIX production following administration of ALA alone show the largest increase in production following the combined administration of ALA and L1. PpIX fluorescence is thought to be a measure of cellular activity and the goal of the current study was to determine which cell lines would be the most promising targets for fluorescence detection or monitoring response to therapy. The results indicate that the cells with larger size and larger numbers of mitochondria may be good potential targets for this therapy. While this conclusion may appear obvious, it is not universally true, and cellular specific variations exist which are still not fully understood.