Synthesis and biological evaluation of 68Ga-DOTA-PLE: a Plectin-1-targeted radiotracer for PET/MR imaging of pancreatic cancer.

PURPOSE: Pancreatic cancer is characterized by high malignancy and diagnostic challenges. Plectin-1 is a specific biomarker significantly overexpressed in pancreatic ductal adenocarcinoma (PDAC). This study aimed to synthesize a Plectin-1-targeting radiotracer, 68Ga-DOTA-PLE, and evaluate its potential for pancreatic cancer imaging. METHODS: The precursor DOTA-PLE was radiolabeled with 68Ga, followed by radiochemical yield and stability evaluated. In vitro binding affinity and in vivo biological properties were evaluated using cell binding assays, pharmacokinetic analysis, biodistribution studies, and micro-PET/MR imaging in Plectin-1-positive BxPC-3 and Plectin-1-negative β-TC-6 models. RESULTS: Radiochemical analysis by radio-HPLC and TLC confirmed that ⁶⁸Ga-DOTA-PLE was obtained with high radiochemical purity with no detectable free ⁶⁸Ga or colloidal species. The tracer demonstrated excellent in vitro stability, maintaining a radiochemical purity (RCP) of > 90% after incubation in PBS and serum at 37 °C for 2 h. In vitro binding assays revealed specific binding of ⁶⁸Ga-DOTA-PLE to Plectin-1, as evidenced by significantly higher uptake in Plectin-1-positive BxPC-3 cells than in Plectin-1-negative β-TC-6 cells (P<0.001). Pharmacokinetic evaluation indicated rapid blood clearance, with distribution (T₁/₂α) and elimination (T₁/₂β) half-lives of 2.99 min and 18.99 min, respectively. Biodistribution studies performed prominent tumor accumulation (4.41 ± 1.05 %ID/g) at 30 min post-injection. while the radiotracer was primarily excreted via the renal pathway (8.65 ± 1.61 %ID/g), exhibiting low hepatic and intestinal background. Micro-PET/MR imaging clearly delineated tumor lesions, and identified 15-30 min post-injection as the optimal imaging window, during which the tumor-to-muscle (T/M) ratio reached its maximum (2.91 ± 0.38).