Initial evaluation of novel 99mTc radiolabeled peptides targeting the neovasculature in an endocrine pancreatic cancer model

Objectives To develop small molecule single photon emission computed tomography (SPECT) imaging probes for angiogenesis with novel peptide sequences specifically targeting neovasculature of endocrine pancreatic cancer.

Methods A selected peptide (CRGRRST) was adapted as a SPECT imaging probe using a single amino acid chelate (SAAC) built in to the peptide backbone and labeled with technetium-99m (Tc-99m) tricarbonyl for in vitro and in vivo evaluations. Biodistribution and SPECT imaging studies were conducted in two tumor stages of RIP-Tag transgenic mouse models.

Results The SAAC-containing peptide demonstrated high labeling efficiency (>90%) with Tc-99m tricarbonyl. The labeled peptide was shown to be completely stable in phosphate buffer over 6 hours with moderate degradation (30%) occurring in mouse plasma over a 30 minute course. SPECT-CT imaging studies were completed 45 min and 2 hours following administration of radiolabeled peptide in RIP-Tag mouse models at both 9-10 weeks and 12-13 weeks of tumor growth. Biodistribution studies showed specific tumor uptake of 3.39±1.23% ID/g at 45 min and 1.63±0.57 %ID/g at 2 hours post-injection for late stage of 12 week tumor mice which was confirmed by autoradiographic correlation and low uptake within whole pancreas at 0.89±0.1%ID/g in normal mice. Moreover, the peptide showed similar homing behavior in mice at early tumor stage.

Conclusions The initial evaluation of 99mTc labeled RGR peptide indicated that it specifically targets pancreatic endocrine tumor at even early stages of tumor development. These findings suggest ahigh potential for neovasculature imaging with 99mTc-CRGRRST as a means of early endocrine pancreatic cancer detection and further studies are warranted in order to improve the probe’s in vivo targeting and detection sensitivity.

Research Support R01CA135358, R01CA119414 and IRG-97-150-10 from the American Cancer Society