{"doi":"10.1007/s00259-025-07110-8","title":"Whole-body PET imaging of simian immunodeficiency virus using gp120-targeting probes fails to reveal regions of specific uptake in rhesus macaques","abstract":"Abstract Purpose Following the initial reports demonstrating the feasibility of immunoPET imaging of simian immunodeficiency virus (SIV) using gp120-targeting monoclonal antibodies in non-human primates, replication efforts of the imaging system in human immunodeficiency virus (HIV)-infected individuals have yielded conflicting results. Herein, we used two anti-gp120 antibodies, 7D3 and ITS103.01LS-F(ab’) 2 , to interrogate the reproducibility of gp120-targeting probes for immunoPET imaging of SIV in rhesus macaques. Methods The binding affinity estimates of 89 Zr radiolabeled 7D3 and ITS103.01LS-F(ab’) 2 to SIV gp120, and the in-vitro and ex-vivo binding specificities of [ 89 Zr]Zr-7D3 and [ 89 Zr]Zr-ITS103.01LS-F(ab’) 2 to SIV Env expressing cells, primary cells, and tissue sections from uninfected and SIV-infected macaques were obtained through competition assays. The biodistributions of [ 89 Zr]Zr-7D3 and [ 89 Zr]Zr-ITS103.01LS-F(ab’) 2 were performed with static PET scans up to 6 days post-injection in 20 rhesus macaques and the standardized uptake values in various tissues were compared between SIV-infected and uninfected controls. Results Despite the demonstrated nanomolar affinity of [ 89 Zr]Zr-7D3 and [ 89 Zr]Zr-ITS103.01LS-F(ab’) 2 to SIV gp120, and strong binding specificity to SIV gp120 cell lines, we observed no discernible differences in their binding in primary cells, tissue sections of secondary lymphoid organs, in-vivo probe uptake between SIV-infected and uninfected macaques, or ex-vivo validation necropsies. While the probes remained stable in-vivo, only [ 89 Zr]Zr-ITS103.01LS-F(ab’) 2 in chronic plasma retained its binding specificity to SIV gp120, with [ 89 Zr]Zr-7D3 experiencing a > 97% reduction in binding to gp120 due to competition from endogenous antibodies at the 7D3 binding site. Conclusion The overall absence of specific uptake suggests inadequate binding potential (ligand affinity x target molarity) for these probes to effectively image SIV or HIV in-vivo, warranting further investigation into the lack of reproducibility observed with earlier non-human primate SIV imaging and conflicting human studies.","journal":"European Journal of Nuclear Medicine and Molecular Imaging","year":2025,"id":533213,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9656,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":945207,"name":"In‐Sook Kim","orcid":"0000-0003-0600-8268","position":1,"is_corresponding":false},{"id":945708,"name":"Hyukjin Jang","orcid":null,"position":2,"is_corresponding":false},{"id":794993,"name":"Paula DeGrange","orcid":"0000-0002-7705-9831","position":3,"is_corresponding":false},{"id":1047569,"name":"Heather Brown","orcid":"0009-0003-5547-9821","position":4,"is_corresponding":false},{"id":1336940,"name":"Viviana Dalton","orcid":null,"position":5,"is_corresponding":false},{"id":1263456,"name":"Yunden Badralmaa","orcid":null,"position":6,"is_corresponding":false},{"id":433365,"name":"Ven Natarajan","orcid":null,"position":7,"is_corresponding":false},{"id":945208,"name":"Brad Long","orcid":"0000-0002-9365-2782","position":8,"is_corresponding":false},{"id":308731,"name":"Jorge A. Carrasquillo","orcid":"0000-0002-8513-5734","position":9,"is_corresponding":false},{"id":794994,"name":"Michele Di Mascio","orcid":"0000-0001-6609-9689","position":10,"is_corresponding":false},{"id":794992,"name":"Sharat Srinivasula","orcid":"0000-0003-1867-5762","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T02:51:32.301795Z","pmid":"39888424","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}