Molecular Imaging of Pancreatic Duct Adenocarcinoma Using [¹⁸F]JR1004, a Cannabinoid Type 2 Receptor Targeted Positron Emission Tomography (PET) Probe

Abstract Purpose Pancreatic ductal adenocarcinoma (PDAC) represents a highly aggressive malignancy with a 5-year survival rate below 10% and poor prognosis. Early diagnosis of PDAC remains a significant challenge due to its nonspecific symptomatology, insufficient reliable biomarkers, aggressive tumor progression with early metastatic spread, and limited effective screening protocols. Recent research indicates cannabinoid type 2 receptor (CB2R) overexpression in PDAC, leading to the development of [¹⁸F]JR1004 as a potential CB2R-targeted PET probe to address diagnostic challenges in this aggressive malignancy. Procedures The probe development utilized computer-aided drug design, incorporating modifications to a triaryl sulfonamide CB2R inverse agonist lead compound. Essential pharmacophoric elements (central sulfonamide, flanking aromatic rings) were preserved, while the para-methoxy group underwent conversion to a tosylate precursor for radiolabeling maintaining electronic properties. Radiolabeling with ¹⁸F was performed using a JiRui OnePlatform 3.1s synthesizer (synthesis time: 70 min). Results The radiochemical purity and yield achieved values exceeding 95% and 16.7%, respectively. In vitro studies confirmed [¹⁸F]JR1004’s specific binding affinity in CB2R-overexpressing cells, with uptake significantly reduced by a CB2R antagonist administration. PET imaging in PDAC mouse models revealed significant accumulation in tumor regions, with receptor specificity validated through CB2R blocking studies. Biodistribution analysis revealed primary probe metabolism through the hepatobiliary system, with maximal uptake in the liver and pancreas. The probe's targeting profile demonstrates notable improvements for PDAC detection compared to the relatively nonspecific uptake patterns of ¹⁸F-FDG PET in pancreatic imaging. Conclusions This investigation presents an innovative molecular imaging approach for early PDAC diagnosis and precision treatment, exhibiting considerable potential for clinical implementation.