In vivo preclinical evaluation of the new 68Ga-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 authors report on synthesis and tumor-targeting properties of PGE2 specific ⁶⁸Ga-labeled NODAGA-randomly methylated beta-cyclodextrin (⁶⁸Ga-NODAGA-RAMEB) [1]. The radiochemical purity 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 NODAGA-RAMEB was − 3.63 ± 0.04.

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. Biodistribution studies showed high accumulation of ⁶⁸Ga-NODAGA-RAMEB in PGE2 positive BxPC-3 tumors; approximately 15–20-fold higher radiotracer uptake was observed, than that of the background.

⁶⁸Ga-labeled RAMEB is a promising radiotracer in PET diagnostics of PGE2 positive tumors.

1. 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 Hajdu:
   In vivo preclinical evaluation of the new 68Ga-labeled beta-cyclodextrin in prostaglandin E2 (PGE2) positive tumor model using positron emission tomography. International Journal of Pharmaceutics 576, 25 February 2020, 118954. https://doi.org/10.1016/j.ijpharm.2019.118954