Abstract
1352
Objectives To investigate if co-administration of tumor-penetrating peptide CRGDKGPDC (iRGD) which has an affinity to integrin αvβ3 could increase the uptake of In-111 labeled B3, a murine IgG1k mAb directed against the Ley antigen, by a αvβ3 and neuropilin-1 dependent mechanism into PC-3 tumor expressing Leyand neuropilin-1 but not integrin αvβ3 on the cell surface.
Methods Groups of nude mice (n=4~5) were inoculated sc with PC-3 tumor cells in the right hind flank. When the mean tumor size was 300mm3, the mice received iv In-111- MX- B3 (3.0μCi/60μg; radiochemical purity, >98%; immunoreactivity, >70%) with and without iRGD (4μmol/kg) on D0. The other iRGD groups received additional iRGD (4µmol/kg) on Ds 1, 2, and/or 3. The biodistribution was performed on Ds 1, 2, 3, and 7.
Results The comparative biodistribution studies of In-111-MX- B3 with and without the iRGD administration showed similar distributions of the radiolabel in blood and organs. The tumor uptakes (% ID/g) for the control without iRGD were 21.66±2.77 on D1, 21.78±4.49 on D2, 18.82±3.88 on D3, and 12.91±3.31 on D7. Compared to the control, the iRGD coadministration and subsequent daily injections of iRGD showed a trend toward increased tumor uptake: the uptake was increased by 14.7% (p=0.274) on D2, 35.6% (p=0.015) on D3 and 27.4% (p=0.120) on D 7.
Conclusions These findings suggest that the tumor uptake of In-111-B3 in PC-3 tumor was primarily mediated by the mAb B3 binding to Ley antigen rather than internalization and penetration mechanism activated by the neuropilin-1 dependent active transport. This study also suggests that additional experiments are needed involving tumor cells that express αvβ3 and neuropilin-1 but not Ley antigen to illustrate the αvβ3 and neuropilin-1 dependent active transport mechanism to increase the uptake of In-111-B3 into tumor.