{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T07:14:33Z","timestamp":1793171673292,"version":"4.5.0"},"reference-count":55,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon Europe Research and Innovation program under the Marie Sk\u0142odowska-Curie Action (OncoProTools)","award":["101073231"],"award-info":[{"award-number":["101073231"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background: FAP radiopharmaceuticals show promise for cancer diagnosis; however, their limited tumor residency hinders treatment. This study compared two FAPi derivatives, DOTA.SA.FAPi and DOTAGA.(SA.FAPi)2, labeled with gallium-68 and lutetium-177, aiming to determine an optimum combination for creating theranostic pairs. Methods: The radiotracers were studied for lipophilicity, binding to human serum proteins, and binding to human cancer-associated fibroblasts (CAFs) in vitro, including saturation and internalization\/externalization studies. PET\/SPECT\/CT and biodistribution studies were conducted in PC3 and U87MG xenografts for [68Ga]Ga-DOTA.SA.FAPi and [68Ga]Ga-DOTAGA.(SA.FAPi)2. [177Lu]Lu-DOTA.SA.FAPi and [177Lu]Lu-DOTAGA.(SA.FAPi)2, were evaluated in PC3 xenografts. Biodistribution studies of [68Ga]Ga-DOTA.SA.FAPi were performed in healthy male and female mice. Results: All radiotracers exhibited strong binding to FAP. Their internalization rate was fast while only [177Lu]Lu-DOTAGA.(SA.FAPi)2 was retained longer in CAFs. [68Ga]Ga-DOTAGA.(SA.FAPi)2 and [177Lu]Lu-DOTAGA.(SA.FAPi)2 displayed elevated lipophilicity and affinity for human serum proteins compared to [68Ga]Ga-DOTA.SA.FAPi and [177Lu]Lu-DOTA.SA.FAPi. In vivo studies revealed slower washout of [68Ga]Ga-DOTAGA.(SA.FAPi)2 within 3 h compared to [68Ga]Ga-DOTA.SA.FAPi. The tumor-to-tissue ratios of [68Ga]Ga-DOTAGA.(SA.FAPi)2 versus [68Ga]Ga-DOTA.SA.FAPi did not exhibit any significant differences. [177Lu]Lu-DOTAGA.(SA.FAPi)2 maintained a significant tumor uptake even after 96 h p.i. compared to [177Lu]Lu-DOTA.SA.FAPi. Conclusions: Dimeric compounds hold promise for therapy, while monomers are better suited for diagnostics. Finding the right combination is essential for effective disease management.<\/jats:p>","DOI":"10.3390\/molecules29133093","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T08:17:29Z","timestamp":1719821849000},"page":"3093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Tailoring Fibroblast-Activation Protein Targeting for Theranostics: A Comparative Preclinical Evaluation of the 68Ga- and 177Lu-Labeled Monomeric and Dimeric Fibroblast-Activation Protein Inhibitors DOTA.SA.FAPi and DOTAGA.(SA.FAPi)2"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7746-1572","authenticated-orcid":false,"given":"Tilman","family":"L\u00e4ppchen","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Inselspital, Bern University Hospital, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrianna","family":"Bilinska","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Inselspital, Bern University Hospital, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirinaios","family":"Pilatis","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Inselspital, Bern University Hospital, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Men\u00e9ndez","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Inselspital, Bern University Hospital, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2520-2146","authenticated-orcid":false,"given":"Surachet","family":"Imlimthan","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Inselspital, Bern University Hospital, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euy Sung","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Chemistry\u2014TRIGA Site, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Afshar-Oromieh","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Inselspital, Bern University Hospital, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"R\u00f6sch","sequence":"additional","affiliation":[{"name":"Department of Chemistry\u2014TRIGA Site, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1954-736X","authenticated-orcid":false,"given":"Axel","family":"Rominger","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Inselspital, Bern University Hospital, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Gourni","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Inselspital, Bern University Hospital, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Imlimthan, S., Moon, E.S., Rathke, H., Afshar-Oromieh, A., R\u00f6sch, F., Rominger, A., and Gourni, E. 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