Abstract
1884
Objectives: RGD peptides are promising probes for targetting and binding to αvβ3 integrin, a cell-surface receptor highly restricted in expression to angiogenic vasculature. Cyclization of RGD-containing peptides has been shown to increase both specificity and affinity for defined integrin subtypes. Cyclo[Arg-Gly-Asp-D-Tyr-(HYNIC)-Lys] (RGDdYK) was preliminarily synthesized and conjugated to HYNIC. The aim was to evaluate 99mTc-HYNIC-RGD analog in nude mice bearing inoculated lung tumor cells A549.
Methods: HYNIC-RGD was labeled with 99mTc using tricine/EDDA as coligands. Radiochemical analysis of 99mTc-peptide was performed by thin-layer chromatography (TLC) with a two solvent system: Methylethylketone (MEK) and Acetonitrile 50%. HPLC and SepPak cartridge were also employed. Biodistribution studies were performed in Swiss mice at three times (2, 4 and 24 hours), and image acquisition was documented at 4 hours.
Results: Radiochemical purity was 99.45 ± 0.12 %. ITLC findings were confirmed by HPLC with a retention time for the product of 12.86 minutes. Only traces (< 0.6 %) of 99mTcO4- could be detected, with a retention time of 5.33 min. Biodistribution in normal Swiss mice showed very fast blood clearance, with prominent radioactivity in kidneys but with liver uptake as well, reflecting the two elimination routes of the tracer. Good tumor imaging was achieved after 4 hours, and ROI was 2.56%.
Conclusions: 99mTc-HYNIC-RGD analog was obtained with very high yield, and the biodistribution pattern was confirmed in the animal model, including favorable tumor uptake. Further studies in tumors where integrins are overexpressed should be done, as the compound targets tumor-associated angiogenesis.
Research Support (if any): Acknowledgement: The study was supported by IAEA within a Co-ordinated Research Project “Development of 99mTc based small Biomolecules using novel 99mTc cores”.
- Society of Nuclear Medicine, Inc.