Copper-64-Labeled 1C1m-Fc, a New Tool for TEM-1 PET Imaging and Prediction of Lutetium-177-Labeled 1C1m-Fc Therapy Efficacy and Safety.

ABSTRACT: 1C1m-Fc, a promising anti-TEM-1 DOTA conjugate, was labeled with ⁶⁴Cu to target cancer cells for PET imaging and predicting the efficacy and safety of a previously studied [¹⁷⁷Lu]Lu-1C1m-Fc companion therapy. DOTA-conjugated 1C1m-Fc was characterized by mass spectrometry, thin layer chromatography and immunoreactivity assessment. PET/CT and biodistribution studies were performed in human neuroblastoma xenografted mice. Absorbed doses were assessed from biodistribution results and extrapolated to ¹⁷⁷Lu based on the [⁶⁴Cu]Cu-1C1m-Fc data. The immunoreactivity was ≥ 70% after 48 h of incubation in serum, and the specificity of [⁶⁴Cu]Cu-1C1m-Fc for the target was validated. High-resolution PET/CT images were obtained, with the best tumor-to-organ ratios reached at 24 or 48 h and correlated with results of the biodistribution study. Healthy organs receiving the highest doses were the liver, the kidneys and the uterus. [⁶⁴Cu]Cu-1C1m-Fc could be of interest to give an indication of ¹⁷⁷Lu dosimetry for parenchymal organs. In the uterus and the tumor, characterized by specific TEM-1 expression, the ¹⁷⁷Lu-extrapolated absorbed doses are overestimated because of the lack of later measurement time points. Nevertheless, 1C1m-Fc radiolabeled with ⁶⁴Cu for imaging would appear as an interesting radionuclide companion for therapeutic application with [¹⁷⁷Lu]Lu-1C1m-Fc.

SUBMITTER: Delage JA 

PROVIDER: S-EPMC8657097 | biostudies-literature |

REPOSITORIES: biostudies-literature