Professor and Distinguished Member, Cellular Stress Biology
Research Professor, Institute of Lasers, Photonics and Biophotonics, SUNY, Buffalo
Roswell Park Cancer Institute
Elm and Carlton Streets
Buffalo, NY 14263, USA
Phone: 716-845-3203
Fax: 715-845-8920
E-mail: ravindra.pandey@roswellpark.org 

After completing a PhD from the University of Rajasthan, Jaipur, India in Medicinal Chemistry, Dr. Pandey worked as a postdoctoral fellow and research associate in the laboratories of Professor Kevin M. Smith (University of California, Davis, 1980-1983 and 1984-1986) and the late Professor A. H. Jackson (University College Cardiff, Wales, 1983-1984) on the chemistry and biochemistry aspects of porphyrin-based compounds. He joined Oncologic Foundation of Buffalo in 1986 and was involved in a photodynamic therapy project related to Photofrin^® research funded by Johnson & Johnson. In 1990 he left the Foundation and joined the Photodynamic Therapy Center, Roswell Park Cancer Institute, Buffalo, where he is currently associated as Distinguished Professor and Director of Pharmaceutical Chemistry, Department of Cell Stress Biology. He also has an appointment as Professor with the Institute of Lasers, Photonics and Biophotonics, SUNY at Buffalo.

Accomplishments:

Dr. Pandey has been working on the synthesis of porphyrin-based compounds for the last 26 years and investigating their application for use in PDT for the last 21 years. His group was responsible for characterizing the active components of Photofrin^®, which also played an important role in its worldwide approval for use in photodynamic therapy. His current research interests are focused on developing “multifunctional agents,” nanoparticles for tumor imaging (PET, MRI, fluorescence)/PDT to develop models for photosynthetic reaction centers and to explore the chemistry of porphyrin-based compounds related to chlorins and bacteriochlorins. Most of the photosensitizers and tumor imaging agents developed in his group are derived from naturally occurring chlorophyll-a and bacteriochlorophyll-a. One of his compounds (HPPH) is currently in Phase II human clinical trials and several more are in various stages of preclinical and toxicological studies.

Dr. Pandey is a member of the editorial boards of the Journal of Porphyrins and Phthalocyanines, Current Organic Chemistry and Current Organic Synthesis. He is a founding member of the International Society of Porphyrins and Phthalocyanines. He has organized several national and international scientific symposiums and has delivered a large number of plenary and invited lectures all over the world on PDT and tumor imaging. He has received several awards including the Inventor of the Year Award (Niagara Frontier), the Rajiv Gandhi Award of Excellence, and “Who's Who in Science.” He has been a reviewer of research grants for various federal agencies (US, UK, Canada, Singapore, France) and private foundations. He has 30 patents to his credit and published over 200 research papers in various reputed international journals, as well as several review articles and book chapters. His research is well funded by national funding agencies and private organizations.

Dr. Pandey is also the founder of Photolitec, LLC, a biotech company. The goal of this organization is to develop cancer imaging and therapeutic agents and also to start clinical trials in developing countries.

Description of Research:

Photosensitizers for Photodynamic Therapy:  For the last several years one of the objectives of Dr. Pandey’s laboratory has been to design and synthesize tumor-avid porphyrin-based photosensitizers for photodynamic therapy (PDT) exhibiting the longest wavelength absorption in the range of 660-800 nm. Such compounds on exposure to light at appropriate wavelengths may enable treatment of large tumors. Therefore, for our studies starting from chlorophyll-a and bacteriochlorophyll-a, we synthesized and evaluated a series of photosensitizers related to pyropheophorbide-a,purpurinamides and bacteriopurpurinimides with long wavelength absorption near 660, 700 and 800 nm respectively. On the basis of SAR and QSAR studies conducted in a highly stimulating collaboration with Drs. Bellnier, Dougherty, Henderson and Baumann of our department, we selected one compound from each series, and these photosensitizers are currently at various stages of clinical and preclinical trials.

Molecular Modeling-Based Target-Specific Photosensitizers: The major challenge of cancer therapy is the selective destruction of malignant cells while sparing normal tissue. While certain photosensitizers show a degree of selectivity, the parameters chosen for treatment in patients are limited by reactions of the normal tissue within the light field. Therefore, one of the objectives of Dr. Pandey's research program has been to improve and optimize PDT by targeting photosensitizers to tumors. His current approach is to target the photosensitizers to integrins (a_vb₃), folate receptors and certain cellular carbohydrate receptors (e.g. galectins) that are over expressed in a variety of malignant tumors. In collaboration with Dr. Shibata (NJ), Dr. Pandey's group is using molecular modeling-based approach for designing target-specific photosensitizers in collaboration with Dr. Shibata (NJ). The initial results are promising.

Bi-Functional Tumor-Imaging (MRI, PET and Fluorescence) and Therapeutic Agents: In recent years, cellular and molecular biology have ushered in a new era for the characterization of the tumor tissue at the molecular level. The non-invasive molecular imaging of the specific type of tumors in vivo followed by tailored medical intervention is becoming the new frontier of cancer treatment. Therefore, for investigating the utility of tumor-avid photosensitizers as vehicles to deliver the imaging agents (MRI, Nuclear Imaging, Optical Imaging) to tumors, HPPH (a chlorophyll-a analog developed in our laboratory currently in Phase I/II human clinical trials) was conjugated with a variety of imaging agents. In preliminary studies, the corresponding conjugates e.g., HPPH-DTPA, was found to be a promising dual function (tumor MR imaging and therapy) agent. We have recently extended this approach for developing tumor specific PET imaging and optical imaging agents. These multidisciplinary projects are in collaboration with Drs. Grossman (Radiology), Kanter (Toxicology), Mazurchuk (MRI Center), Oseroff and Morgan (Dermatology), Lamonica (Nuclear Medicine), Bellnier (PDT), Sen (Tumor Biology), Ramaprasad (University of Nebraska), Achilefu (Washington Univ., St. Louis), and Drs. Sajjad and Nabi (SUNY at Buffalo).

PDT and Nanotechnology: In collaboration with the Biophotonics group at SUNY Buffalo, and Dr. Kopelman’s group at the University of Michigan, his group has recently initiated a research project to investigate the utility of nanotechnology in developing agents for tumor imaging and phototherapy (PDT). Collaborators: Drs. Prasad, Bergey and group (SUNY Buffalo); Dr. Kopelman (University of Michigan); and Drs. Oseroff and Morgan (Dermatology, RPCI).

Models for Photosynthetic Reaction Centers: Other research interests of Dr. Pandey’s group are (i) to develop new methodologies for the synthesis of porphyrin-fullerene based compounds as monomers, dimers and higher oligomers as models for photosynthetic reaction centers, (ii) to investigate their spectroscopic and electron-transfer characteristics and (iii) to develop efficient models for photosynthetic reaction centers. Collaborators: Dr. Fukuzumi, (Universitiy of Osaka, Japan) and Dr. Kadish (University of Houston).

Recent Publications (click here to view a list of Dr. Pandey's research from PubMed):

Photodynamic Therapy:

• Purpurinimide carbohydrate conjugates: Effect of the position of the carbohydrate moiety in photosensitizing efficacy. Molecular Pharmaceutics. 2007, 4, 448-464.
• Structure-activity relationship among purpurinimides and bacteriopurpurinimides: Trifluoromethyl substituent enhanced the photosensitizing efficacy. J. Med. Chem. 2007, 50, 1754-1767.
• The Tyrosine kinase inhibitor imatanib mesylate enhances the efficacy of photodynamic therapy by inhibiting ABCG2. Clin Cancer Research. 2007, 13, 2463-2470.
• Comparative in vitro and in vivo studies of long wavelength photosensitizers derived from bacteriochloropurpurinimide and bacteriochlorin p6: Fused imide ring enhances the in vivo PDT efficacy. Bioconjugate chemistry, 2007, 18, 1460-1473.
• Nature: A rich source for developing multifunctional agents. Tumor imaging and PDT. Lasers in Surgery and Medicine. 2006, 38, 445-467.
• In vivo stability and photodynamic efficacy of fluorinated bacteriopurpurinimides derived from bacteriochlorophyll-a. J. Med. Chem. 2006, 49, 1874-1881.
• Methyl Pheophobide-a analogs: Potential fluorescent probes for the peripheral benzodiazepine receptors. Effect of central metal in photosensitizing efficacy. J. Med. Chem. 2005, 48, 3692-3696 (rapid publication).

Multifunctional Agents:

(a)  Optical Imaging with and without PDT:

• Photophysical, electrochemical characteristics and cross-linking of STAT-3 protein by an efficient bifunctional agent for fluorescent image-guided PDT. Photochemical and Photobiological Sciences, 2007, In Press.
• A novel approach to a bifunctional photosensitizer for tumor imaging and phototherapy. Bioconjugate Chemistry, 2005, 16, 1264-1274.
• Utility of tumor-avid photosensitizers in developing bifunctional agents for tumor imaging and/or phototherapy. Proceedings of SPIE, 2006, 6139, 613905.

(b)  PET Imaging with and without PDT:

• Multimodality agents for tumor imaging (PET, fluorescence) and PDT. A possible “see and Treat” approach. J. Med. Chem. 2005,48,6286-6295.

(c)  MR Imaging with and without PDT:

• Chlorophyll-a analogs conjugated with aminobenzyl-DTPA as potential bifunctional agents for magnetic resonance imaging and photodynamic therapy. Bioconjugate Chem. 2005, 16, 32-42.

(d)  Nanoparticles:

• Organically modified nanoparticles with covalently incorporated photosensitizer for photodynamic therapy of cancer. Nanoletters, 2007, 7, 2835-2842.
• Organically modified silica nanoparticles co-encapsulating photosensitizing drug and aggregation-enhanced teo-photon absorbing fluorescent dye aggregates for two-photon photodynamic therapy. J. Am. Chem. Soc. 2007, 129, 2669-2675.
• New method for delivering a hydrophobic drug for PDT using pure nanocrystal form of the drug. Molecular Pharmaceutics. 2007, 4, 289-297.
• Diacyllipid miscelle-based nanocarrier for magnetically guided delivery of drugs in PDT. Molecular Pharmaceutiucs, 2006, 3(4):415-423.