{"doi":"10.3390/pharmaceutics14030666","title":"Nonpeptidic Z360-Analogs Tagged with Trivalent Radiometals as Anti-CCK2R Cancer Theranostic Agents: A Preclinical Study","abstract":"(1) Background: Theranostic approaches in the management of cholecystokinin subtype 2 receptor (CCK2R)-positive tumors include radiolabeled gastrin and CCK motifs. Moving toward antagonist-based CCK2R-radioligands instead, we herein present three analogs of the nonpeptidic CCK2R-antagonist Z360, GAS1/2/3. Each was conjugated to a different chelator (DOTA, NODAGA or DOTAGA) for labeling with medically relevant trivalent radiometals (e.g., Ga-68, In-111, Lu-177) for potential use as anti-CCK2R cancer agents; (2) Methods: The in vitro properties of the thee analogs were compared in stably transfected HEK293-CCK2R cells. Biodistribution profiles were compared in SCID mice bearing twin HEK293-CCK2R and wtHEK293 tumors; (3) Results: The GAS1/2/3 analogs displayed high CCK2R-affinity (lower nM-range). The radioligands were fairly stable in vivo and selectively targeted the HEK293-CCK2R, but not the CCK2R-negative wtHEK293 tumors in mice. Their overall pharmacokinetic profile was found strongly dependent on the radiometal-chelate. Results could be visualized by SPECT/CT for the [111In]In-analogs; (4) Conclusions: The present study highlighted the high impact of the radiometal-chelate on the end-pharmacokinetics of a new series of Z360-based radioligands, revealing candidates with promising properties for clinical translation. It also provided the impetus for the development of a new class of nonpeptidic radioligands for CCK2R-targeted theranostics of human cancer.","journal":"Pharmaceutics","year":2022,"id":272571,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":939122,"name":"Panagiotis Kanellopoulos","orcid":"0000-0002-0617-3936","position":1,"is_corresponding":false},{"id":429774,"name":"Oleg G. Chepurny","orcid":"0009-0002-2003-0752","position":2,"is_corresponding":false},{"id":939123,"name":"Maritina Rouchota","orcid":"0000-0003-1988-0426","position":3,"is_corresponding":false},{"id":939124,"name":"George Loudos","orcid":"0000-0002-2441-115X","position":4,"is_corresponding":false},{"id":429775,"name":"George G. Holz","orcid":"0000-0002-1781-3580","position":5,"is_corresponding":false},{"id":939594,"name":"Eric P. Krenning","orcid":null,"position":6,"is_corresponding":false},{"id":939125,"name":"Θεοδοσία Μάινα","orcid":"0000-0002-1123-2486","position":7,"is_corresponding":false},{"id":939121,"name":"Berthold A. Nock","orcid":"0000-0002-6028-9112","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T00:27:47.926496Z","pmid":"35336041","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":[]}