{"doi":"10.2967/jnumed.120.246926","title":"Predicting Gemcitabine Delivery by<sup>18</sup>F-FAC PET in Murine Models of Pancreatic Cancer","abstract":"<sup>18</sup>F-FAC (2′-deoxy-2′-<sup>18</sup>F-fluoro-β-d-arabinofuranosylcytosine) has close structural similarity to gemcitabine and thus offers the potential to image drug delivery to tumors. We compared tumor <sup>18</sup>F-FAC PET images with <sup>14</sup>C-gemcitabine levels, established ex vivo, in 3 mouse models of pancreatic cancer. We further modified tumor gemcitabine levels with injectable PEGylated recombinant human hyaluronidase (PEGPH20) to test whether changes in gemcitabine would be tracked by <sup>18</sup>F-FAC. <b>Methods:</b><sup>18</sup>F-FAC was synthesized as described previously. Three patient-derived xenograft (PDX) models were grown in the flanks of NSG mice. Mice were given PEGPH20 or vehicle intravenously 24 h before coinjection of <sup>18</sup>F-FAC and <sup>14</sup>C-gemcitabine. Animals were euthanized and imaged 1 h after tracer administration. Tumor and muscle uptake of both <sup>18</sup>F-FAC and <sup>14</sup>C-gemcitabine was obtained ex vivo. The efficacy of PEPGPH20 was validated through staining with hyaluronic acid binding protein. Additionally, an organoid culture, initiated from a KPC (Pdx-1 Cre LSL-Kras<sup>G12D</sup> LSL-p53<sup>R172H</sup>) tumor, was used to generate orthotopically growing tumors in C57BL/6J mice, and these tumors were then serially transplanted. Animals were injected with PEGPH20 and <sup>14</sup>C-gemcitabine as described above to validate increased drug uptake by ex vivo assay. PET/MR images were obtained using a PET insert on a 7-T MR scanner. Animals were imaged immediately before injection with PEGPH20 and again 24 h later. <b>Results:</b> Tumor-to-muscle ratios of <sup>14</sup>C-gemcitabine and <sup>18</sup>F-FAC correlated well across all PDX models and treatments (<i>R</i><sup>2</sup> = 0.78). There was a significant increase in the tumor PET signal in PEGPH20-treated PDX animals, and this signal was matched in ex vivo counts for 2 of 3 models. In KPC-derived tumors, PEGPH20 raised <sup>14</sup>C-gemcitabine levels (tumor-to-muscle ratio of 1.9 vs. 2.4, control vs. treated, <i>P</i> = 0.013). PET/MR <sup>18</sup>F-FAC images showed a 12% increase in tumor <sup>18</sup>F-FAC uptake after PEGPH20 treatment (<i>P</i> = 0.023). PEGPH20-treated animals uniformly displayed clear reductions in hyaluronic acid staining. <b>Conclusion:</b><sup>18</sup>F-FAC PET was shown to be a good surrogate for gemcitabine uptake and, when combined with MR, to successfully determine drug uptake in tumors growing in the pancreas. PEGPH20 had moderate effects on tumor uptake of gemcitabine.","journal":"Journal of Nuclear Medicine","year":2020,"id":89160,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":255788,"name":"Milan Grkovski","orcid":"0000-0001-7228-9497","position":1,"is_corresponding":false},{"id":452177,"name":"Isabella O’Donoghue","orcid":null,"position":2,"is_corresponding":false},{"id":451222,"name":"Teja Kalidindi","orcid":"0000-0002-0210-0270","position":3,"is_corresponding":false},{"id":291557,"name":"Nagavarakishore Pillarsetty","orcid":"0000-0002-1750-7436","position":4,"is_corresponding":false},{"id":451223,"name":"Eva Burnazi","orcid":"0000-0003-3089-0959","position":5,"is_corresponding":false},{"id":218301,"name":"Amanda Kulick","orcid":"0000-0001-7365-4142","position":6,"is_corresponding":false},{"id":452178,"name":"Amber Bahr","orcid":null,"position":7,"is_corresponding":false},{"id":451224,"name":"Qing Chang","orcid":"0000-0001-7406-8479","position":8,"is_corresponding":false},{"id":451225,"name":"H. Carl LeKaye","orcid":"0000-0001-7495-8199","position":9,"is_corresponding":false},{"id":225995,"name":"Elisa de Stanchina","orcid":"0000-0002-3873-315X","position":10,"is_corresponding":false},{"id":242188,"name":"Kenneth H. Yu","orcid":"0000-0002-4774-2672","position":11,"is_corresponding":false},{"id":255807,"name":"John L. Humm","orcid":"0000-0003-4245-5591","position":12,"is_corresponding":false},{"id":228775,"name":"James Russell","orcid":"0000-0003-0827-1801","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T22:01:50.225871Z","pmid":"32646874","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":[]}