In Vivo Investigation of Gallium-68 and Bismuth-205/206 Labeled Beta Cyclodextrin for Targeted Alpha Therapy of Prostaglandin E2 Receptor-Expressing Tumors in Mice.

Prostaglandin E2 (PGE2) molecule and its receptors play an important role in the development of malignancies and metastases therefore PGE2 may play a crucial role in the diagnosis and a new therapeutic target in the field of radionuclide therapy of PGE2-positive tumors. PGE2 form complexes with RAMEB (randomly-methylated-beta-cyclodextrin) with high affinity therefore the aim of this present study was to synthesize a PGE2-specific DOTAGA-RAMEB, which can be labeled with diagnostic and therapeutic isotopes also and binds to PGE2-positive tumors. DOTAGA-RAMEB was labeled with 68Ga and Bi-205/206 radionuclides and their radiochemical purity (RCP%), partition coefficient (logP values), and in vitro and in vivo stability were determined. For the assessment of the biological properties and the PGE2 specificity of [Ga-68]Ga-DOTAGA-RAMEB and [Bi-205/206]Bi-DOTAGA-RAMEB in vivo PET imaging and ex vivo biodistribution studies were performed using healthy control and PGE2-positive BxPC-3 tumor-bearing CB17 SCID mice. The RCP% of the newly synthesized [Ga-68]Ga-DOTAGA-RAMEB and [Bi-205/206]Bi-DOTAGA-RAMEB was higher than 98 %. In vivo studies showed that the tumor-to-background ratio of [Ga-68]Ga-DOTAGA-RAMEB was 2.5 +/- 0.2 as a result BxPC-3 tumors were clearly identified on PET images. Beside this the ex vivo biodistribution studies showed that the accumulation rate of [Ga-68]Ga-DOTAGA-RAMEB and [Bi-205/206]Bi-DOTAGA-RAMEB was similar in the PGE2-positive BxPC-3 tumors.