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D'Souza JW , Hensley H , Doss M , Beigarten C , Torgov M , Olafsen T , Yu JQ , Robinson MK
Cerenkov Luminescence Imaging as a Modality to Evaluate Antibody-Based PET Radiotracers
J Nucl Med. 2017 Jan;58(1) :175-180
PMID: 27539844 PMCID: PMC5209641 URL: https://www.ncbi.nlm.nih.gov/pubmed/27539844
AbstractAntibodies, and engineered antibody fragments, labeled with radioisotopes are being developed as radiotracers for the detection and phenotyping of diseases such as cancer. The development of antibody-based radiotracers requires extensive characterization of their in vitro and in vivo properties, including their ability to target tumors in an antigen-selective manner. In this study, we investigated the use of Cerenkov luminescence imaging (CLI) as compared with PET as a modality for evaluating the in vivo behavior of antibody-based radiotracers. METHODS: The anti-prostate-specific membrane antigen (PSMA) huJ591 antibody (IgG; 150 kDa) and its minibody (Mb; 80 kDa) format were functionalized with the chelator 1,4,7-triazacyclononane-1-glutaric acid-4,7-diacetic acid (NODAGA) and radiolabeled with the positron-emitting radionuclide 64Cu (half-life, 12.7 h). Immunoreactive preparations of the radiolabeled antibodies were injected into NCr nu/nu mice harboring PSMA-positive CWR22Rv1 and PSMA-negative PC-3 tumor xenografts. Tumor targeting was evaluated by both PET and CLI. RESULTS: 64Cu-NODAGA-PSMA-IgG and 64Cu-NODAGA-PSMA-Mb retained the ability to bind cell surface PSMA, and both radiotracers exhibited selective uptake into PSMA-positive tumors. Under the experimental conditions used, PSMA-selective uptake of 64Cu-NODAGA-PSMA-IgG and 64Cu-NODAGA-PSMA-Mb was observed by CLI as early as 3 h after injection, with tumor-to-background ratios peaking at 24 (IgG) and 16 (Mb) h after injection. Targeting data generated by CLI correlated with that generated by PET and necropsy. CONCLUSION: CLI provided a rapid and simple assessment of the targeting specificity and pharmacokinetics of the antibody-based PET radiotracers that correlated well with the behavior observed by standard PET imaging. Moreover, CLI provided clear discrimination between uptake kinetics of an intact IgG and its small-molecular-weight derivative Mb. These data support the use of CLI for the evaluation of radiotracer performance.
NotesD'Souza, Jimson W Hensley, Harvey Doss, Mohan Beigarten, Charles Torgov, Michael Olafsen, Tove Yu, Jian Q Robinson, Matthew K eng 2016/08/20 06:00 J Nucl Med. 2017 Jan;58(1):175-180. doi: 10.2967/jnumed.116.178780. Epub 2016 Aug 18.