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In the present study, the copper(I)\u2010catalyzed azide\u2013alkyne cycloaddition was applied for the development of a modular molecular platform for medical imaging of the prostate\u2010specific membrane antigen (PSMA), using positron emission tomography. This process is shown from molecular design, through synthesis automation and <jats:italic>in vitro<\/jats:italic> studies, all the way to pre\u2010clinical <jats:italic>in vivo<\/jats:italic> evaluation of fluorine\u201018\u2010 labeled PSMA\u2010targeting \u2018F\u2010PSMA\u2010MIC\u2019 radiotracers (t<jats:sub>1\/2<\/jats:sub>=109.7\u2005min). Pre\u2010clinical data indicate that the modular PSMA\u2010scaffold has similar binding affinity and imaging properties to the clinically used [<jats:sup>68<\/jats:sup>Ga]PSMA\u201011. Furthermore, we demonstrated that targeting the arene\u2010binding in PSMA, facilitated through the [3+2]cycloaddition, can improve binding affinity, which was rationalized by molecular modeling. The here presented PSMA\u2010binding scaffold potentially facilitates easy coupling to other medical imaging moieties, enabling future developments of new modular imaging agents.<\/jats:p>","DOI":"10.1002\/chem.202001795","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T12:21:14Z","timestamp":1587471674000},"page":"10871-10881","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Modular Medical Imaging Agents Based on Azide\u2013Alkyne Huisgen Cycloadditions: Synthesis and Pre\u2010Clinical Evaluation of <sup>18<\/sup>F\u2010Labeled PSMA\u2010Tracers for Prostate Cancer Imaging"],"prefix":"10.1002","volume":"26","author":[{"given":"Verena I.","family":"B\u00f6hmer","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging Department of Radiology Department of Surgical Oncology University of Groningen University Medical Center Groningen  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