Preclinical Evaluation of 18F-Fluoroethyl-β-D-Lactose in Pancreatic Carcinoma

Objectives The early diagnosis of pancreatic cancer is crucial for the reduction of mortality and morbidity for the patients. However, the most widely used PET (positron emission tomography) tracer, ¹⁸F-FDG was not able to detect some pancreatic tumors that are not FDG avid. A recently reported lactose analogue, ¹⁸F-FEL (¹⁸F-2-fluoroethyl-β-D-lactose), which binds to hepatocellular carcinoma-intestine-pancreas and pancreatitis-associated proteins (HIP/PAP), seems to be a promising tracer capable of imaging of pancreatic carcinomas. In this study, automatic synthesis, preclinical evaluation of the probe in detecting pancreatic carcinoma xenografts in mice were conducted.

Methods A multifunctional synthesis module was used for the radiolabeling of ¹⁸F-FEL starting from ¹⁸F ion using a one-pot fully automated reactions and the product was analyzed by radio-TLC. Additional competitions studies in vitro, investigations on the metabolic stability in vivo, ¹⁸F-FEL microPET scans (Fig. A&D), comparative ¹⁸F-FDG microPET (Fig. C&E), and competitive studies of ¹⁸F-FEL in vivo (Fig. B) were performed in nude mice bearing T3M4 pancreatic carcinoma (Fig. A-C, pancreatic carcinoma in right upper arm, and turpentine-induced inflammation in left hind leg), and SKBR3 breast carcinoma xenografts (Fig. D&E). In the in vivo blocked study, β-D-lactose (15 mg/kg) was coinjected with ¹⁸F-FEL (100 μCi) before the microPET images were acquired. HIP/PAP expression on T3M4 and SKBR3 tumor sections were determined by immunohistochemical stainning (IHC).

Results The average radiochemical yield was of 20 ± 5% (n = 10, non-decay-corrected) with the specific activity greater than 14.2 ± 7.1 GBq/μmol. Synthesis time was approximately 30 min from the end of bombardment. ¹⁸F-FEL exhibits high HIP/PAP affinity with a half maximum inhibitory concentration (IC50) of 22 ± 3.89 nM. The percentage of intact probe was no less than 94% for the in vivo stability test. ¹⁸F-FEL showed low uptake in nontumor tissue and particularly low non-sterile inflammation tissue accumulation leading to high-contrast delineation of tumors in micro-PET studies. The radiotracer was rapidly cleared from circulation and excreted mainly through the urinary system. In competitive studies, the tumor-to-muscle ratio was reduced by approximately 80% in xenografts coinjected with β-D-lactose (Table). High HIP/PAP expression in T3M4 tumors, and almost none expression in SKBR3 tumors, were confirmed by IHC staining.

Conclusions Conclusions: A simple 2-step automatic radiosynthesis of ¹⁸F-FEL has been accomplished with high yield and purity. These studies indicate that ¹⁸F-FEL is a promising and specific probe for non-invasive imaging of HIP/PAP-expressing pancreatic carcinoma by PET, and shows potentially advantage over FDG in differentiation tumor from inflammation.