(18)F-labeled Dimer-Sansalvamide A Cyclodecapeptide: A Novel Diagnostic Probe to Discriminate Pancreatic Cancer from Inflammation in a Nude Mice Model

Early detection of pancreatic cancer has been a long-standing challenge. Inflammatory mass is the main source of false-positive findings in (18)F-labeled fluorodeoxyglucose ((18)F-FDG) positron emission tomography / computed tomography (PET/CT). Heat shock protein 90 (Hsp90) is an established biomarker overexpressed in pancreatic cancer. We modified a Dimer-Sansalvamide A cyclodecapeptide by conjugating it with the bifunctional chelator NOTA (1,4,7-triazacyclononane-1,4,7-trisacetic acid), yielding (18)F-NOTA-Dimer-Sansalvamide A cyclodecapeptide ((18)F-NOTA-Dimer-San A). The binding specificity of the probe was confirmed by in vitro cell uptake assays in Hsp90-positive PL45 pancreatic cancer cells. Hsp90 expression was imaged via MicroPET in pancreatic cancer xenografts and inflammation in mice. All of the mice received an intravenous injection of (18)F-NOTA-Dimer-San A, and images were acquired at 1 and 2 hour time points. The novel probe demonstrated prominent tumor uptake in the pancreatic cancer xenografts (4.00 ± 0.88 %ID/g, 5.80 ± 0.94 %ID/g), and the inflammatory thigh showed minimal uptake (0.85 ± 0.01 %ID/g, 1.50 ± 0.20 %ID/g) at 1 and 2 hours after injection, respectively. The activity accumulation between the two groups was significantly different (P < 0.05), and the biodistribution data was consistent with the images. Moreover, immunohistochemistry (IHC) confirmed that the expression of Hsp90 was positive in PL45 pancreatic cancer but negative in the muscles next to the tumor and inflammatory muscles. We concluded that (18)F-NOTA-Dimer-San A PET might allow non-invasive imaging for Hsp90 expression in tumors and has the potential to discriminate pancreatic cancer from inflammatory mass.