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

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 synthetize the PGE2 specific ⁶⁸ Ga-labeled NODAGA-randomly methylated beta-cyclodextrin ( ⁶⁸ Ga-NODAGA-RAMEB) and investigate its tumor-targeting properties. NODAGA-RAMEB was labeled with Gallium-68 ( ⁶⁸ Ga), and the radiochemical purity (RCP%), partition coefficient (logP values), and in vitro-in vivo stability of ⁶⁸ Ga-NODAGA-RAMEB were determined. After intravenous injection of ⁶⁸ Ga-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 ⁶⁸ Ga-NODAGA-RAMEB was higher than 98%. The molar activity was 15.34 ± 1.93 GBq/μmol. The logP of ⁶⁸ Ga labeled NODAGA-RAMEB was - 3.63 ± 0.04. Biodistribution studies showed high accumulation of ⁶⁸ Ga-NODAGA-RAMEB in PGE2 positive BxPC-3 tumors; approximately 15-20-fold higher radiotracer uptake was observed, than that of the background. ⁶⁸ Ga-labeled RAMEB is a promising radiotracer in PET diagnostics of PGE2 positive tumors.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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