The non-invasive molecular imaging of the specific type of tumor in vivo followed by tailored medical invention is becoming the new frontier in cancer treatment. Our preliminary study indicates that tumoravid porphyrin-based compounds (e.g. HPPH, a chlorophyll-a analog) can be used as a vehicle to deliver the radionuclide to tumors. The biodistribution results indicate that the tumor/non-tumor uptake ration of the drug depend on time and tumor size. The time for tumor imaging was found to be an important parameter because, with time the clearance of the photosensitizer from tumor was found to be slower than most of the non-tumor tissues. Therefore, for further studies replacing """"""""To (half-life 6 hours) with longer-lived isotope such as ln-111 could provide a useful scanning agent. In preliminary in vivo study compared to HPPH, the corresponding nonradioactive In(lll) complex produced a 10-fold increase in in vivo photosensitizing efficacy with no significant skin phototoxicity on day 3. Ina parallel study, we were able to convert the 3-iodobenzylether group into the corresponding 1-124 analog with high specificity. In preliminary in vitro as well as in vivo screening, this compound (non-radioactive analog) was found to be quite effective. In a comparative study with [ F]FDG, the corresponding 1-124 photosensitizer showed better tumor specificity (see Preliminary Results). Another approach for developing an improved tumor-imaging and phototherapy agents (bifunctional agents) could be to replace HPPH with those compounds that exhibit a significantly higher tumor to nontumor ratio and produce long-wavelength absorption near 750-800 nm (light treatment at this wavelength could be useful for treating large tumors and those that are deeply seated. The comparative study of the conjugate will include: tumor uptake by in vivo reflectance spectroscopy, tumor imaging, in vitro and in vivo PDT efficacy, skin phototoxicity, biodistribution study and general toxicity. The development of tumor imaging or improved photodynamic therapy agent(s) by itself represents an important step, but a dual function agent (SPECT/PDT or PET/PDT) provides the potential for diagnostic body scan followed by targeted therapy. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA114053-02
Application #
7175447
Study Section
Special Emphasis Panel (ZRG1-ONC-J (04))
Program Officer
Menkens, Anne E
Project Start
2006-02-02
Project End
2010-01-30
Budget Start
2007-02-01
Budget End
2010-01-30
Support Year
2
Fiscal Year
2007
Total Cost
$180,131
Indirect Cost
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
824771034
City
Buffalo
State
NY
Country
United States
Zip Code
14263
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Pandey, Ravindra K; James, Nadine S; Chen, Yihui et al. (2010) Bifunctional agents for imaging and therapy. Methods Mol Biol 635:223-59
Pandey, Suresh K; Sajjad, Munawwar; Chen, Yihui et al. (2009) Comparative positron-emission tomography (PET) imaging and phototherapeutic potential of 124I- labeled methyl- 3-(1'-iodobenzyloxyethyl)pyropheophorbide-a vs the corresponding glucose and galactose conjugates. J Med Chem 52:445-55
Pandey, Suresh K; Sajjad, Munawwar; Chen, Yihui et al. (2009) Compared to purpurinimides, the pyropheophorbide containing an iodobenzyl group showed enhanced PDT efficacy and tumor imaging (124I-PET) ability. Bioconjug Chem 20:274-82
Zheng, Xiang; Pandey, Ravindra K (2008) Porphyrin-carbohydrate conjugates: impact of carbohydrate moieties in photodynamic therapy (PDT). Anticancer Agents Med Chem 8:241-68
Liu, Chao; Dobhal, Mahabeer P; Ethirajan, Manivannan et al. (2008) Highly selective synthesis of the ring-B reduced chlorins by ferric chloride-mediated oxidation of bacteriochlorins: effects of the fused imide vs isocyclic ring on photophysical and electrochemical properties. J Am Chem Soc 130:14311-23
Pandey, Ravindra K; Goswami, Lalit N; Chen, Yihui et al. (2006) Nature: a rich source for developing multifunctional agents. Tumor-imaging and photodynamic therapy. Lasers Surg Med 38:445-67