Evaluation of technetium-99M labeled RGD-containing peptide as potential tumor imaging agents in tumor-bearing mice

Integrins (especially αvβ3) play a important role in angiogenesis, growth and metastasis of a solid tumor. Targeting tumor with radiolabeled ligands of the αVβ3 integrin may provide information about the receptor status and enable specific therapeutic strategy. A tripeptidic sequence Arg-Gly-Asp (RGD) is often the primary site of recognition by integrins. The aim of this study examine 99mTc-labeled elevenfold peptide (GRGDSRGDSCY, GY11) that target the αVβ3 integrin to determine if this agent target tumors for diagnostic imaging and/or targeted radiotherapy of cancer. Methods: GY11 was radiolabelled with 99Tcm via cystine residue by means of stannous chloride. 99Tcm-GY11 was injected through tail vein into nude mice bearing A375 human melanoma. Biodistribution was investigated at 1,2,4 and 6 hours after injection. Percentage injected dose/gram of tissue (%ID/g) and tumor/non-tumor ratios were calculated. Planar images were acquired with SPECT at 1,2,4,6hrs, respectively. Results: 99Tcm-GY11 was rapidly cleared from blood and excreted predominantly from the kidney. Tumor uptake at 2h postinjection was 3.1%ID/g. The ratios of tumor/blood and tumor/muscle increased from 0.9-6.2, 4.3-13.5 from 1-6hrs postinjection, respectively. Planar images confirmed that tumor could be visualized at 4h after administration of 99Tcm-GY11. Conclusion: The results suggest that 99Tcm-GY11 is a promising compound for noninvasive determining the αVβ3 integrin status. 99Tcm-GY11 SPECT may be useful to imaging αVβ3-positive tumor and also guide proper utility of αVβ3 antagonist therapy and radionuclide therapy for cancer. (authors)