Evaluation of 134 Ce as a PET imaging surrogate for antibody drug conjugates incorporating 225 Ac

The in vivo generator Ce/ La has the potential to serve as a PET imaging surrogate for both alpha-emitting Ac and Th radionuclides due to the unique Ce /Ce redox couple and the relatively long half-life of Ce. The purpose of this study was to demonstrate the compatibility of Ce with DOTA-based antibody drug conjugates, which would act as therapeutic agents when incorporating Ac. The in vivo biodistributions of [ Ce]Ce-DOTA and [ Ce]Ce-citrate were assayed by microPET imaging over 25 h in Swiss Webster mice to determine the in vivo stability of the [ Ce]Ce-DOTA complex. L -edge X-ray absorption spectroscopy measurements were used to confirm the Ce oxidation state and the formation of a fully coordinated Ce-DOTA complex. The in vivo biodistribution of [ Ce]Ce-DOTA-Trastuzumab was assayed over 147 h by microPET imaging in SK-OV-3 tumor-bearing NOD SCID mice to evaluate tumor uptake and in vivo stability. Mice were euthanized at 214 h after administration of the radiolabeled antibody conjugate, and imaged 1 h later. An ex vivo biodistribution experiment was then performed in order to corroborate the PET images. [ Ce]Ce-DOTA displayed rapid renal elimination and high in vivo stability over 25 h, with negligible bone and liver uptake, in comparison to [ Ce]Ce-citrate. L -edge X-ray absorption spectroscopy experiments confirmed the 3+ oxidation state within the stable Ce-DOTA complex. MicroPET images of [ Ce]Ce-DOTA-Trastuzumab displayed elevated tumor uptake over 214 h, with minimal bone and liver uptake analogous to previously reported [ Ac]Ac-DOTA-Trastuzumab biodistribution results, and the ex vivo biodistribution of [ Ce]Ce-DOTA-Trastuzumab corroborated the final PET images. These results demonstrate that Ce allows for long-term tumor targeting with DOTA-based antibody drug conjugates and may therefore be used to trace antibody drug conjugates incorporating Ac.