Abstract
1147
Objectives: Integrin αvβ3 is a very important receptor overexpressed in angiogenic and many tumor cells. Porphyrin based photosensitizers are useful agents for fluorescence imaging of cancer. Porphyrins are also excellent metal chelators forming highly stable metal-complexes making them efficient delivery vehicles for radioisotopes such as 64Cu. Here our aim is to synthesis and evaluate a new tracer that combined porphyrins with peptide 3PRGD2 radiolabeled with 64Cu for PET and fluorescence imaging of αvβ3.
Methods: Porphyrin-3PRGD2 was synthesized by solid phase peptide synthesis and radiolabelled with 64Cu on a 20 μg scale in 0.1 M NH4OAc buffer (pH = 5.5)at 100oC in 30 min and purified by Sep-Pak C18 cartridge .After cooling to room temperature, the resulting solution was analyzed by radio-HPLC. Porphyrin-3PRGD2(≍20nm/ml) was incubation with αvβ3-positive U87MG cells in 2 h at 37 ℃ and using confocal fluorescence microscopy to see the targeting efficacy. 64Cu - porphyrin-3PRGD2 for in vivo MicroPET and fluorescence imaging in U87MG tumor-bearing mice with RGD blocking studies conducted to confirm the integrin αVβ3specificity.
Results: 64Cu-porphyrin-3PRGD2 can be prepared in a very high radiochemical purity after purified by Sep-Pak C18 cartridge(>95%). The tumors were clearly visualized by both the MicroPET and fluorescence imaging .The cell confocal fluorescence imaging consistent with the multimodal imaging results. Blocking study showed a significant inhibition of U87MG tumor uptake, indicating it is integrin αvβ3 mediated. Conclusion: Possessing dual PET and fluorescence imaging, 64Cu-porphyrin-3PRGD2 is very promising for tumor diagnosis. This study confirmed that 64Cu-porphyrin-3PRGD2 can serve as a safe cancer diagnosis agent with cancer-targeting ability and using the tracer in the mice for the Photodynamic therapy is in progress.