{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:25:33Z","timestamp":1789719933492,"version":"4.0.1"},"reference-count":88,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T00:00:00Z","timestamp":1591660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The folate receptor-\u03b1 (FR-\u03b1) is overexpressed in many epithelial cancers, including ovary, uterus, kidneys, breast, lung, colon and prostate carcinomas, but shows limited expression in normal tissues such as kidneys, salivary glands, choroid plexus and placenta. FR-\u03b1 has therefore emerged as a promising target for the delivery of therapeutic and imaging agents to FR-positive tumors. A series of folate-based PET (positron emission tomography) radiopharmaceuticals have been developed for the selective targeting of FR-positive malignancies. This review provides an overview on the research progress made so far regarding the design, radiosynthesis and the utility of the folate-derived PET radioconjugates for targeting FR-positive tumors. For the most part, results from folate radioconjugates labeled with fluorine-18 (t1\/2 = 109.8 min) and gallium-68 (t1\/2 = 67.7 min) have been presented but folates labeled with \u201cexotic\u201d and new PET radionuclides such as copper-64 (t1\/2 = 12.7 h), terbium-152 (t1\/2 = 17.5 h), scandium-44 (t1\/2 = 3.97 h), cobalt-55 (t1\/2 = 17.5 h) and zirconium-89 (t1\/2 = 78.4 h) are also discussed. For tumor imaging, none of the reported PET radiolabeled folates reported to date has made the complete bench-to-bedside journey except [18F]AzaFol, which made it to patients with metastatic ovarian and lung cancers in a multicenter first-in-human trial. In the near future, however, we expect more clinical trials with folate-based PET radiopharmaceuticals given the increasing clinical interest in imaging and the treatment of FR-related malignancies.<\/jats:p>","DOI":"10.3390\/cancers12061508","type":"journal-article","created":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T05:11:46Z","timestamp":1591765906000},"page":"1508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Development of Folate Receptor\u2212Targeted PET Radiopharmaceuticals for Tumor Imaging\u2014A Bench-to-Bedside Journey"],"prefix":"10.3390","volume":"12","author":[{"given":"Silvan D.","family":"Boss","sequence":"first","affiliation":[{"name":"SWAN Isotopen AG, University Hospital Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon Mensah","family":"Ametamey","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zurich, 8093 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"52553","DOI":"10.18632\/oncotarget.9651","article-title":"Targeting folate receptor alpha for cancer treatment","volume":"7","author":"Cheung","year":"2016","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"480","DOI":"10.3109\/00498254.2013.845705","article-title":"Folate, folic acid and 5-methyltetrahydrofolate are not the same thing","volume":"44","author":"Scaglione","year":"2014","journal-title":"Xenobiotica"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1146\/annurev.nutr.19.1.91","article-title":"Carrier-mediated membrane transport of folates in mammalian cells","volume":"19","author":"Sirotnak","year":"1999","journal-title":"Annu. Rev. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.4161\/cbt.22020","article-title":"The human proton-coupled folate transporter: Biology and therapeutic applications to cancer","volume":"13","author":"Desmoulin","year":"2012","journal-title":"Cancer Biol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1146\/annurev.nu.16.070196.002441","article-title":"Folate Receptors","volume":"16","author":"Antony","year":"1996","journal-title":"Annu. Rev. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0378-1119(00)00418-2","article-title":"Identification of two putative novel folate receptor genes in humans and mouse","volume":"258","author":"Spiegelstein","year":"2000","journal-title":"Gene"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1042\/bj20020512","article-title":"The human reduced folate carrier gene is ubiquitously and differentially expressed in normal human tissues: Identification of seven non-coding exons and characterization of a novel promoter","volume":"367","author":"Whetstine","year":"2002","journal-title":"Biochem. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1462399409000969","article-title":"Membrane transporters and folate homeostasis: Intestinal absorption and transport into systemic compartments and tissues","volume":"11","author":"Zhao","year":"2009","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"G660","DOI":"10.1152\/ajpgi.00309.2007","article-title":"Functional characterization of PCFT\/HCP1 as the molecular entity of the carrier-mediated intestinal folate transport system in the rat model","volume":"294","author":"Inoue","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ab.2004.12.026","article-title":"Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay","volume":"338","author":"Parker","year":"2005","journal-title":"Anal. Biochem."},{"key":"ref_11","first-page":"3396","article-title":"Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues","volume":"52","author":"Weitman","year":"1992","journal-title":"Cancer Res."},{"key":"ref_12","first-page":"6708","article-title":"Cellular localization of the folate receptor: Potential role in drug toxicity and folate homeostasis","volume":"52","author":"Weitman","year":"1992","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/ar3312","article-title":"A folate receptor beta-specific human monoclonal antibody recognizes activated macrophage of rheumatoid patients and mediates antibody-dependent cell-mediated cytotoxicity","volume":"13","author":"Feng","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1021\/ar7000815","article-title":"Discovery and Development of Folic-Acid-Based Receptor Targeting for Imaging and Therapy of Cancer and Inflammatory Diseases","volume":"41","author":"Low","year":"2008","journal-title":"Accounts Chem. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.2174\/138161212799315777","article-title":"Folate based radiopharmaceuticals for imaging and therapy of cancer and inflammation","volume":"18","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.addr.2004.02.003","article-title":"Folate receptor-targeted drugs for cancer and inflammatory diseases","volume":"56","author":"Low","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s10555-008-9155-6","article-title":"Tumor detection using folate receptor-targeted imaging agents","volume":"27","author":"Sega","year":"2008","journal-title":"Cancer Metastasis Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.cbpa.2009.03.022","article-title":"Folate-targeted therapeutic and imaging agents for cancer","volume":"13","author":"Low","year":"2009","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6811","DOI":"10.1021\/jm100509v","article-title":"Folate-targeted therapies for cancer","volume":"53","author":"Xia","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.3390\/molecules18055005","article-title":"Folate-based radiotracers for PET imaging\u2014Update and perspectives","volume":"18","year":"2013","journal-title":"Molecules"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.addr.2004.01.008","article-title":"Folate-targeted chemotherapy","volume":"56","author":"Leamon","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S0969-8051(03)00080-5","article-title":"Preparation of 66Ga- and 68Ga-labeled Ga(III)-deferoxamine-folate as potential folate-receptor-targeted PET radiopharmaceuticals","volume":"30","author":"Mathias","year":"2003","journal-title":"Nucl. Med. Biol."},{"key":"ref_23","first-page":"1210","article-title":"64Cu-Labeled folate-conjugated shell cross-linked nanoparticles for tumor imaging and radiotherapy: Synthesis, radiolabeling, and biologic evaluation","volume":"46","author":"Rossin","year":"2005","journal-title":"J. Nucl. Med."},{"key":"ref_24","first-page":"1153","article-title":"Synthesis and preclinical evaluation of a folic acid derivative labeled with 18F for PET imaging of folate receptor-positive tumors","volume":"47","author":"Bettio","year":"2006","journal-title":"J. Nucl. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1021\/bc800356r","article-title":"Fluorine-18 click radiosynthesis and preclinical evaluation of a new 18F-labeled folic acid derivative","volume":"19","author":"Ross","year":"2008","journal-title":"Bioconjug. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/jlcr.1022","article-title":"Novel synthesis of [18F]-fluorobenzene and pyridinecarbohydrazide-folates as potential PET radiopharmaceuticals","volume":"49","author":"Okarvi","year":"2006","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.nucmedbio.2011.03.004","article-title":"Rapid synthesis and in vitro and in vivo evaluation of folic acid derivatives labeled with fluorine-18 for PET imaging of folate receptor-positive tumors","volume":"38","author":"Amer","year":"2011","journal-title":"Nucl. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s00259-010-1597-8","article-title":"Development of new folate-based PET radiotracers: Preclinical evaluation of 68Ga-DOTA-folate conjugates","volume":"38","author":"Fani","year":"2011","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1021\/mp200418f","article-title":"In vivo imaging of folate receptor positive tumor xenografts using novel 68Ga-NODAGA-folate conjugates","volume":"9","author":"Fani","year":"2012","journal-title":"Mol. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.2967\/jnumed.112.107540","article-title":"A unique matched quadruplet of terbium radioisotopes for PET and SPECT and for \u03b1- and \u03b2--radionuclide therapy: An in vivo proof-of-concept study with a new receptor-targeted folate derivative","volume":"53","author":"Zhernosekov","year":"2012","journal-title":"J. Nucl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1021\/bc200660z","article-title":"[18F]Fluoro-deoxy-glucose folate: A novel PET radiotracer with improved in vivo properties for folate receptor targeting","volume":"23","author":"Fischer","year":"2012","journal-title":"Bioconjug. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.nucmedbio.2012.02.005","article-title":"Novel synthesis and preclinical evaluation of folic acid derivatives labeled with 18F-[FDG] for PET imaging of folate receptor-positive tumors","volume":"39","author":"Amer","year":"2012","journal-title":"Nucl. Med. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/ar4191","article-title":"Evaluation of the novel folate receptor ligand [18F]fluoro-PEG-folate for macrophage targeting in a rat model of arthritis","volume":"15","author":"Gent","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s11307-013-0651-x","article-title":"Improved PET imaging of tumors in mice using a novel 18F-folate conjugate with an albumin-binding entity","volume":"15","author":"Fischer","year":"2013","journal-title":"Mol. Imaging Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.1021\/mp4001684","article-title":"Comparative analysis of folate derived PET imaging agents with [18F]-2-fluoro-2-deoxy-D-glucose using a rodent inflammatory paw model","volume":"10","author":"Kularatne","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Schieferstein, H., Fischer, C.R., Ross, T.L., and Betzel, T. (2013). 18F-click labeling and preclinical evaluation of a new 18F-folate for PET imaging. EJNMMI Res., 3.","DOI":"10.1186\/2191-219X-3-68"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.2967\/jnumed.113.123810","article-title":"Promises of cyclotron-produced 44Sc as a diagnostic match for trivalent \u03b2--emitters: In vitro and in vivo study of a 44Sc-DOTA-folate conjugate","volume":"54","author":"Bunka","year":"2013","journal-title":"J. Nucl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1002\/mabi.201400200","article-title":"18F-Radiolabeling, preliminary evaluation of folate-pHPMA conjugates via PET","volume":"14","author":"Schieferstein","year":"2014","journal-title":"Macromol. Biosci."},{"key":"ref_39","first-page":"6547","article-title":"Development and pre-clinical evaluation of new 68Ga-NOTA-folate Conjugates for PET imaging of folate receptor-positive tumors","volume":"34","author":"Amer","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1021\/acs.molpharmaceut.6b00143","article-title":"64Cu- and 68Ga-based PET imaging of folate receptor-positive tumors: Development and evaluation of an albumin-binding NODAGA\u2013folate","volume":"13","author":"Farkas","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.apradiso.2016.07.024","article-title":"Synthesis and evaluation of a 68Ga labeled folic acid derivative for targeting folate receptors","volume":"116","author":"Jain","year":"2016","journal-title":"Appl. Radiat. Isot."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1021\/acs.molpharmaceut.5b00989","article-title":"Synthesis and preclinical evaluation of folate-NOTA-Al18F for PET imaging of folate receptor-positive tumors","volume":"13","author":"Chen","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1021\/acs.bioconjchem.5b00644","article-title":"Comparative studies of three pairs of \u03b1- and \u03b3-conjugated folic acid derivatives labeled with fluorine-18","volume":"27","author":"Boss","year":"2016","journal-title":"Bioconjug. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1007\/s11307-017-1049-y","article-title":"Development of a new folate-derived Ga-68-based PET imaging agent","volume":"19","author":"Brand","year":"2017","journal-title":"Mol. Imaging Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4353","DOI":"10.1021\/acs.molpharmaceut.7b00415","article-title":"Folate-PEG-NOTA-Al18F: A new folate based radiotracer for PET imaging of folate receptor-positive tumors","volume":"14","author":"Chen","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6113","DOI":"10.1039\/C7NR09269E","article-title":"64Cu-Labeled multifunctional dendrimers for targeted tumor PET imaging","volume":"10","author":"Ma","year":"2018","journal-title":"Nanoscale"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kettenbach, K., Reffert, L.M., Schieferstein, H., Pektor, S., Eckert, R., Miederer, M., R\u00f6sch, F., and Ross, T.L. (2018). Comparison study of two differently clicked 18F-folates\u2014Lipophilicity plays a key role. Pharmaceuticals, 11.","DOI":"10.3390\/ph11010030"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/jlcr.3563","article-title":"Synthesis and evaluation of 68Ga-HBED-CC-EDBE-folate for positron-emission tomography imaging of overexpressed folate receptors on CT26 tumor cells","volume":"61","author":"Choi","year":"2018","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Radford, L.L., Fernandez, S., Beacham, R., El Sayed, R., Farkas, R., Bene\u0161ov, M., M\u00fcller, C., and Lapi, S.E. (2019). New 55Co-labeled albumin-binding folate derivatives as potential PET agents for folate receptor imaging. Pharmaceuticals, 12.","DOI":"10.3390\/ph12040166"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3996","DOI":"10.1021\/acs.molpharmaceut.9b00653","article-title":"Folate receptor \u03b1-targeted 89Zr-M9346A immuno-PET for image-guided intervention with mirvetuximab soravtansine in triple-negative breast cancer","volume":"16","author":"Heo","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/bkcs.10794","article-title":"In vitro PET\/MRI diagnosis and targeted chemotherapy for cancer using radiolabeled nanoprobe: A theragnostic approach","volume":"37","author":"Cho","year":"2016","journal-title":"Korean Chem. Soc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1166\/jnn.2020.17205","article-title":"Synthesis of 64Cu-radiolabeled folate-conjugated iron oxide nanoparticles for cancer diagnosis","volume":"20","author":"Park","year":"2020","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/jlcr.3410","article-title":"Synthesis and biological evaluation of 68Ga-labeled pteroyl-Lys conjugates for folate receptor-targeted tumor imaging","volume":"59","author":"Zhang","year":"2016","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1007\/s00259-006-0111-9","article-title":"Preclinical evaluation of novel organometallic 99mTc-folate and 99mTc-pteroate radiotracers for folate receptor-positive tumour targeting","volume":"33","author":"Hohn","year":"2006","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/jlcr.3116","article-title":"Preparation and biological evaluation of 99mTcN-labeled pteroyl-lys derivative as a potential folate receptor imaging agent","volume":"57","author":"Chen","year":"2014","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7421","DOI":"10.1021\/ja043006n","article-title":"Targeting the tumor-associated folate receptor with an 111In-DTPA conjugate of pteroic acid","volume":"127","author":"Ke","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1016\/j.bmcl.2011.02.014","article-title":"The synthesis of pteroyl-lys conjugates and its application as technetium-99m labeled radiotracer for folate receptor-positive tumor targeting","volume":"21","author":"Guo","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.2967\/jnumed.110.079756","article-title":"A new 18F-labeled folic acid derivative with improved properties for the PET imaging of folate receptor-positive tumors","volume":"51","author":"Ross","year":"2010","journal-title":"J. Nucl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1021\/bc300483a","article-title":"Radiosynthesis and preclinical evaluation of 3\u2032-aza-2\u2032-[18F]fluorofolic acid: A novel PET radiotracer for folate receptor targeting","volume":"24","author":"Betzel","year":"2013","journal-title":"Bioconjug. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.nucmedbio.2011.12.003","article-title":"A fast chemoenzymatic synthesis of [11C]-N5,N10-methylenetetrahydrofolate as a potential PET tracer for proliferating cells","volume":"39","author":"Saeed","year":"2012","journal-title":"Nucl. Med. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.2967\/jnumed.111.099390","article-title":"A folate receptor-\u03b1-specific ligand that targets cancer tissue and not sites of inflammation","volume":"53","author":"Vaitilingam","year":"2012","journal-title":"J. Nucl. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1021\/acs.bioconjchem.7b00775","article-title":"Reduced 18F-folate conjugates as a new class of PET tracers for folate receptor imaging","volume":"29","author":"Boss","year":"2018","journal-title":"Bioconjug. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"135","DOI":"10.2967\/jnumed.118.213314","article-title":"Diastereomerically pure 6R- and 6S-3\u2032-Aza-2\u2032-18F-fluoro-5-methyltetrahydrofolates show unprecedentedly high uptake in folate receptor-positive KB tumors","volume":"60","author":"Boss","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nature12327","article-title":"Structural basis for molecular recognition of folic acid by folate receptors","volume":"500","author":"Chen","year":"2013","journal-title":"Nature"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.addr.2004.01.003","article-title":"Antifolates targeted specifically to the folate receptor","volume":"56","author":"Jackman","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.addr.2004.01.004","article-title":"Folate-receptor-targeted radionuclide imaging agents","volume":"56","author":"Ke","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_67","first-page":"76","article-title":"Imaging of folate receptor with I-125 labeled folate using small animal imaging system built with plastic scintillating optical fibers","volume":"2281","author":"Kulkarni","year":"1994","journal-title":"SPIE"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/S0969-8051(03)00117-3","article-title":"The folate receptor as a molecular target for tumor-selective radionuclide delivery","volume":"30","author":"Ke","year":"2003","journal-title":"Nucl. Med. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jmir.2013.11.002","article-title":"The diagnostic application of radiolabelled folate in the detection of folate receptor-positive tumors","volume":"45","author":"Taylor","year":"2014","journal-title":"J. Med. Imaging Radiat. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2967\/jnumed.110.076018","article-title":"Folic acid conjugates for nuclear imaging of folate receptor-positive cancer","volume":"52","author":"Schibli","year":"2011","journal-title":"J. Nucl. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1021\/bc9500709","article-title":"Synthesis, purification, and tumor cell uptake of 67Ga-deferoxamine-folate, a potential radiopharmaceutical for tumor imaging","volume":"7","author":"Wang","year":"1996","journal-title":"Bioconjug. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Siwowska, K., Schmid, R., Cohrs, S., Schibli, R., and M\u00fcller, C. (2017). Folate receptor-positive gynecological cancer cells: In vitro and in vivo characterization. Pharmaceuticals, 10.","DOI":"10.3390\/ph10030072"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1002\/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4","article-title":"A stepwise huisgen cycloaddition process: Copper(I)-catalyzed regioselective \u201cligation\u201d of azides and terminal alkynes","volume":"41","author":"Rostovtsev","year":"2002","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"35035","DOI":"10.1074\/jbc.M205854200","article-title":"Albumin binding as a general strategy for improving the pharmacokinetics of proteins","volume":"277","author":"Dennis","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"124","DOI":"10.2967\/jnumed.112.107235","article-title":"DOTA Conjugate with an albumin-binding entity enables the first folic acid-targeted 177Lu-radionuclide tumor therapy in mice","volume":"54","author":"Struthers","year":"2013","journal-title":"J. Nucl. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-57841-x","article-title":"First in man study of [18F]fluoro-PEG-folate PET: A novel macrophage imaging technique to visualize rheumatoid arthritis","volume":"10","author":"Verweij","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.5012\/bkcs.2013.34.11.3243","article-title":"Folate receptor-specific positron emission tomography imaging with folic acid-conjugated tissue inhibitor of metalloproteinase-2","volume":"34","author":"Kim","year":"2013","journal-title":"Bull. Korean Chem. Soc."},{"key":"ref_78","first-page":"427","article-title":"99mTc-Ethylenedicysteine-Folate: A new tumor imaging agent. Synthesis, labeling and evaluation in animals","volume":"13","author":"Ilgan","year":"1998","journal-title":"Cancer Biother. Radiopharm."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1021\/bc0200430","article-title":"Synthesis and biological evaluation of EC20: A new folate-derived, 99mTc-based radiopharmaceutical","volume":"13","author":"Leamon","year":"2002","journal-title":"Bioconjug. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"899","DOI":"10.2967\/jnumed.107.049478","article-title":"Exploratory study of 99mTc-EC20 imaging for identifying patients with folate receptor-positive solid tumors","volume":"49","author":"Fisher","year":"2008","journal-title":"J. Nucl. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1007\/s12149-015-1006-2","article-title":"Phase I clinical trial of 99mTc-etarfolatide, an imaging agent for folate receptor in healthy Japanese adults","volume":"29","author":"Yamada","year":"2015","journal-title":"Ann. Nucl. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1093\/annonc\/mdu024","article-title":"Phase II study of treatment of advanced ovarian cancer with folate-receptor-targeted therapeutic (vintafolide) and companion SPECT-based imaging agent (99mTc-etarfolatide)","volume":"25","author":"Morris","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4709","DOI":"10.1039\/C6CS00492J","article-title":"Fluorine-18 labelled building blocks for PET tracer synthesis","volume":"46","author":"Pees","year":"2017","journal-title":"Chem. Soc. Rev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s10967-009-0410-2","article-title":"Nucleophilic aromatic substitution by [18F]fluoride at substituted 2-nitropyridines","volume":"283","author":"Malik","year":"2009","journal-title":"J. Radioanal. Nucl. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"27S","DOI":"10.2967\/jnumed.116.186791","article-title":"Identification of ligands and translation to clinical applications","volume":"58","author":"Haberkorn","year":"2017","journal-title":"J. Nucl. Med."},{"key":"ref_86","first-page":"S219","article-title":"First-in-Human Study with 18F-Azafol for Folate Receptor Targeted PET: An Interim-Analysis of the PET_FOL_1 Phase-I Trial","volume":"45","author":"Meisel","year":"2018","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13550-020-00624-2","article-title":"Radiation dosimetry of 18F-AzaFol: A first in-human use of a folate receptor PET tracer","volume":"10","author":"Gnesin","year":"2020","journal-title":"EJNMMI Res."},{"key":"ref_88","first-page":"1062","article-title":"First-in-human PET imaging study using [68Ga]-folate tracer, [68Ga]EC2115","volume":"60","author":"Cohen","year":"2019","journal-title":"J. Nucl. Med."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/6\/1508\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:37:07Z","timestamp":1760175427000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/6\/1508"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,9]]},"references-count":88,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["cancers12061508"],"URL":"https:\/\/doi.org\/10.3390\/cancers12061508","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,9]]}}}