In vivo preclinical evaluation of the new Ga-68-labeled beta-cyclodextrin in prostaglandin E2 (PGE2) positive tumor model using positron emission tomography

摘要

The cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway plays an important role in tumor development and formation of metastases. It was earlier reported that cyclodextrin derivatives have a high affinity to form complexes with PGE2. Based on these results radiolabeled cyclodextrins - as new radiopharmaceuticals - may open a new pathway in the in vivo imaging and diagnosis of PGE2 positive tumors. The aims of this study were to synthesize the PGE2 specific Ga-68-labeled NODAGA-randomly methylated beta-cyclodextrin (Ga-68-NODAGA-RAMEB) and investigate its tumor-targeting properties. NODAGA-RAMEB was labeled with Gallium-68 (Ga-68), and the radiochemical purity (RCP%), partition coefficient (logP values), and in vitro-in vivo stability of Ga-68-NODAGA-RAMEB were determined. After intravenous injection of Ga-68-NODAGA-RAMEB the accumulation in organs and tissues was monitored in vivo by positron emission tomography (PET) and ex vivo by gamma counter in BxPC-3 and PancTu-1 tumor-bearing CB17 SCID mice. The RCP% of the newly synthesized Ga-68-NODAGA-RAMEB was higher than 98%. The molar activity was 15.34 +/- 1.93 GBq/mu mol. The logP of Ga-68 labeled NODAGA-RAMEB was - 3.63 +/- 0.04. Biodistribution studies showed high accumulation of Ga-68-NODAGA-RAMEB in PGE2 positive BxPC-3 tumors; approximately 15-20-fold higher radiotracer uptake was observed, than that of the background. Ga-68-labeled RAMEB is a promising radiotracer in PET diagnostics of PGE2 positive tumors.