ORGN 191 |
| Ravindra K Pandey1, Guolin Li1, Peter Kanter2, and Zachary Grossman3. (1) PDT Center, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, (2) Experimental Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, (3) Radiology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 |
| In our initial study, an effective photosensitizer, HPPH (a chlorophyll-a derivative) was conjugated with Gd (III)-aminophenylDTPA, an imaging agent. In vivo reflection spectroscopy confirmed that tumor uptake of the HPPH-aminophenylDTPA Gd (III) conjugate was higher than that of HPPH alone in the radiation-induced fibrosarcoma (RIF) tumor of C3H mice. The subcutaneously-implanted Ward colon carcinoma in rats showed markedly increased MRI signal at twenty-four hours after intravenous injection of the conjugate. Both in vitro (RIF tumor cells) and in vivo (mice bearing RIF tumors) the conjugate produced significant efficacy. We have also synthesized a “higher payload” molecule [two Gd (III) atoms per HPPH molecule] that also remained tumor-avid, PDT-active, and with improved MRI enhancing ability than the related mono-Gd(III) analog. Unfortunately, at the MRI dose (10 mmole/kg), these conjugates produced severe skin phototoxicity. However, replacing the hexyl- group of the pyropheophorbide-a with a PEG group, produced remarkable tumor enhancing at 8 hour postinjection, significant tumoricidal activity (80% of mice were free on day 90) with reduced skin phototoxicity than the related hexyl- ether analogs. The development of a tumor-avid contrast medium for MRI would by itself represent an important step in the diagnosis of cancer, but a dual function agent presents the potential for a diagnostic body scan followed by targeted photodynamic therapy, combining two modalities into a single cost-effective “see and treat” approach |
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Chemistry and Biological Applications of Imaging Agents and Molecular Beacons
1:25 PM-5:10 PM, Monday, March 29, 2004 Anaheim Convention Center -- Ballroom C, Oral
Division of Organic Chemistry |