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

Publication date: Available online 11 January 2020Source: International Journal of PharmaceuticsAuthor(s): György Trencsényi, Adrienn Kis, Judit P. Szabó, Ágnes Ráti, Katalin Csige, Éva Fenyvesi, Lajos Szente, Milo Malanga, Gábor Méhes, Miklós Emri, István Kertész, Miklós Vecsernyés, Ferenc Fenyvesi, István HajduAbstractThe 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 synthetize the PGE2 specific 68Ga-labeled NODAGA-randomly methylated beta-cyclodextrin (68Ga-NODAGA-RAMEB) and investigate its tumor-targeting properties. NODAGA-RAMEB was labeled with Gallium-68 (68Ga), and the radiochemical purity (RCP%), partition coefficient (logP values), and in vitro-in vivo stability of 68Ga-NODAGA-RAMEB were determined. After intravenous injection of 68Ga-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 68Ga-NODAGA-RAMEB was higher than 98%. The molar activity was 15.34±1.93 GBq/μmol. The logP of 68Ga labeled NO...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research