Frederick T. Chin, Ph.D.

Publication Details

• 18F-Labeled Cystine Knot Peptides for PET Imaging of Integrin αvβ6.

  Hackel BJ, Kimura RH, Miao Z, Sathirachinda A, Chin FT, Gambhir SS. J Nucl Med. 2013 In Press

  Integrin αvβ6 is a cell-surface receptor with low levels in healthy tissue but elevated expression in lung, colon, skin, ovarian, cervical, and pancreatic cancers. Pancreatic cancer is of particular interest because of the critical need for a molecular imaging agent for early detection as 80% of pancreatic cancers have local advancement or metastasis at time of presentation. Thus, a radiotracer for integrin αvβ6 would provide significant clinical utility. Here we evaluated two cystine knot peptides, R01 and S02, previously engineered with 3-6 nM affinity for integrin αvβ6, for 18F radiolabeling and microPET imaging of BxPC3 pancreatic adenocarcinoma xenografts in mice. Cystine knot peptides were labeled with N-succinimidyl-4-18F-fluorobenzoate at 93% (18F-FB-R01) and 99% (18F-FB-S02) purity. 18F-FB-R01 and 18F-FB-S02 were 87% and 94% stable in human serum at 37º for 2 h. 18F-FB-peptides (2-3 MBq) were injected via tail-vein into nude mice, and exhibited 2.3±0.6 %ID/g and 1.3±0.4 %ID/g, respectively, in BxPC3 xenografted tumors at 0.5 h (n=4-5). Target specificity was confirmed by low tumor uptake in integrin αvβ6-negative 293 tumors (1.4±0.6 and 0.5±0.2 %ID/g for 18F-FB-Ro1 and 18F-FB-So2, both P<0.05; n=3-4) and low muscle uptake (3.1±1.0 and 2.7±0.4 tumor:muscle for 18F-FB-R01 and 18F-FB-S02). MicroPET data were corroborated by ex vivo gamma counting of dissected tissues, which demonstrated low uptake in non-target tissues with only modest kidney uptake (9.2±3.3 and 1.9±1.2 %ID/g at 2 h for 18F-FB-Ro1 and 18F-FB-So2; n=8). Uptake in healthy pancreas was low (0.3±0.1% for 18F-FB-R01 and 0.03±0.01% for 18F-FB-S02; n=8). Thus, these cystine knot peptide tracers, in particular 18F-FB-Ro1, show translational promise for molecular imaging of integrin αvβ6 overexpression in pancreatic and other cancers.