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) . 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.
- 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