{"doi":"10.3390/ph14040358","title":"Feasibility of Developing Radiotracers for MDM2: Synthesis and Preliminary Evaluation of an 18F-Labeled Analogue of the MDM2 Inhibitor SP-141","abstract":"Murine double minute 2 (MDM2), a negative regulator of the p53 tumor suppressor protein, is overexpressed in several human cancers. Herein we investigate the feasibility of developing 18F-labeled compounds based on the small molecule inhibitor SP-141 for imaging tumor MDM2 expression levels with positron emission tomography (PET). Three nonradioactive fluorinated SP-141 analogues, 1–3, were synthesized, and their binding to the MDM2 protein was analyzed by surface plasmon resonance (SPR). One of these, a fluoroethoxy analogue, was labeled with fluorine-18 (18F) using 18F-fluorethyl bromide to provide [18F]1 and evaluated in vitro and in vivo. SPR analysis confirmed the binding of the fluorinated analogues to MDM2 at 1.25–20 µM concentrations. Cell uptake studies revealed high uptake (67.5–71.4%/mg protein) and specificity of [18F]1 in MCF7 and HepG2 cells. The uptake of [18F]1 in these cells could be modulated using 100 µM SP-141, potentially reflecting changes in MDM2 expression because of p53 activation by SP-141. [18F]1 exhibited stable uptake and retention in HepG2 tumor xenografts (~3 %ID/g) in vivo, but poor clearance from blood and other normal tissues, yielding low tumor-to-background ratios (<2) at 2 h post injection. Our results suggest that [18F]1 has suboptimal characteristics for in vivo evaluation as a PET tracer for MDM2, but warrant radiolabeling and assessment of the other fluorinated analogues synthesized in this work, 2 and 3, and potentially other molecular scaffolds for developing MDM2 targeted radiotracers.","journal":"Pharmaceuticals","year":2021,"id":203404,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":510452,"name":"Zhengyuan Zhou","orcid":"0000-0001-9572-5642","position":1,"is_corresponding":false},{"id":642735,"name":"Brian Watts","orcid":"0000-0003-1731-2441","position":2,"is_corresponding":false},{"id":510362,"name":"Michael R. Zalutsky","orcid":"0000-0002-5456-0324","position":3,"is_corresponding":false},{"id":784613,"name":"Satish K. Chitneni","orcid":"0000-0003-1183-2286","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-18T23:51:18.050175Z","pmid":"33924734","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":[]}