1. Medical Imaging Department, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, China.
2. Department of Nuclear Medicine, Taizhou People's Hospital, Taizhou, 225300, China.
3. Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, 90033, USA.
4. Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, 730000, China.
Early detection of pancreatic cancer has been a long-standing challenge. Inflammatory mass is the main source of false-positive findings in 18F-labeled fluorodeoxyglucose (18F-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 18F-NOTA-Dimer-Sansalvamide A cyclodecapeptide (18F-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 18F-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 18F-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.
Keywords: Positron emission tomography (PET), heat shock protein 90 (Hsp90), pancreatic cancer, Dimer-Sansalvamide A cyclodecapeptide, 18F labeling