Pilot-phase PET/CT study targeting integrin α v β 6 in pancreatic cancer patients using the cystine-knot peptide–based 18 F-FP-R 0 1-MG-F2

Purpose A novel cystine-knot peptide–based PET radiopharmaceutical, 18 F-FP-R 0 1-MG-F2 (knottin), was developed to selectively bind to human integrin α v β 6 which is overexpressed in pancreatic cancer. The purpose of this study is to evaluate the safety, biodistribution, dosimetry, and lesion uptake of 18 F-FP-R 0 1-MG-F2 in patients with pancreatic cancer. Methods Fifteen patients (6 men, 9 women) with histologically confirmed pancreatic cancer were prospectively enrolled and underwent knottin PET/CT between March 2017 and February 2021 (ClinicalTrials.gov Identifier NCT02683824). Vital signs and laboratory results were collected before and after the imaging scans. Maximum standardized uptake values (SUV max ) and mean SUV (SUV mean ) were measured in 24 normal tissues and pancreatic cancer lesions for each patient. From the biodistribution data, the organ doses and whole-body effective dose were calculated using OLINDA/EXM software. Results There were no significant changes in vital signs or laboratory values that qualified as adverse events or serious adverse events. At 1 h post-injection, areas of high 18 F-FP-R 0 1-MG-F2 uptake included the pituitary gland, stomach, duodenum, kidneys, and bladder (average SUV mean : 9.7–14.5). Intermediate uptake was found in the normal pancreas (average SUV mean : 4.5). Mild uptake was found in the lungs and liver (average SUV mean < 1.0). The effective dose was calculated to be 2.538 × 10 −2 mSv/MBq. Knottin PET/CT detected all known pancreatic tumors in the 15 patients, although it did not detect small peri-pancreatic lymph nodes of less than 1 cm in short diameter in two of three patients who had lymph node metastases at surgery. Knottin PET/CT detected distant metastases in the lungs ( n = 5), liver ( n = 4), and peritoneum ( n = 2), confirmed by biopsy and/or contrast-enhanced CT. Conclusion 18 F-FP-R 0 1-MG-F2 is a safe PET radiopharmaceutical with an effective dose comparable to other diagnostic agents. Evaluation of the primary pancreatic cancer and distant metastases with 18 F-FP-R 0 1-MG-F2 PET is feasible, but larger studies are required to define the role of this approach. Trial registration NCT02683824.