Synthesis and Preclinical Evaluation of Three Novel ⁶⁸Ga-Labeled Bispecific PSMA/FAP-Targeting Tracers for Prostate Cancer Imaging
department or school: Medicine, Faculty of
data provider: DSpace
identifier citation: Molecules 28 (3): 1088 (2023)
contributor: BC Cancer Research Centre. Molecular Oncology
contributor: BC Cancer Agency
creator: Verena, Arsyangela
creator: Zhang, Zhengxing
creator: Kuo, Hsiou-Ting
creator: Merkens, Helen
creator: Zeisler, Jutta
creator: Wilson, Ryan
creator: Bendre, Shreya
creator: Wong, Antonio A. W. L.
creator: Bénard, François
creator: Lin, Kuo-Shyan
issued: 2025-02-07T17:05:28Z
issued: 2023-01-21
description: Tumor heterogeneity limits the efficacy and reliability of monospecific radiopharmaceuticals in prostate cancer diagnosis and therapy. To overcome this limitation and improve lesion detection sensitivity, we developed and evaluated three bispecific radiotracers that can target both prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP), which are the two key proteins overexpressed in prostate cancer. Three FAP-targeting ligands with various linker lengths were synthesized through multistep organic synthesis, and then connected to the PSMA-targeting motif. IC₅₀(PSMA) and IC₅₀(FAP) values of Ga-complexed bispecific ligands, ⁶⁸Ga-AV01017, ⁶⁸Ga-AV01030, and ⁶⁸Ga-AV01038 were 25.2–71.6 and 1.25–2.74 nM, respectively. The uptake values in PSMA-expressing LNCaP tumor xenografts were 4.38 ± 0.55, 5.17 ± 0.51, and 4.25 ± 0.86 %ID/g for [⁶⁸Ga]Ga-AV01017, [⁶⁸Ga]Ga-AV01030, and [⁶⁸Ga]Ga-AV01038, respectively, which were lower than the monospecific PSMA-targeting tracer [⁶⁸Ga]Ga-HTK03041 (23.1 ± 6.11 %ID/g). The uptake values in FAP-expressing HEK293T:hFAP tumor xenografts were 2.99 ± 0.37, 3.69 ± 0.81, 3.64 ± 0.83 %ID/g for [⁶⁸Ga]Ga-AV01017, [⁶⁸Ga]Ga-AV01030, and [⁶⁸Ga]Ga-AV01038, respectively, which were also lower than the monospecific FAP-targeting tracer, [⁶⁸Ga]Ga-FAPI-04 (12.5 ± 2.00 %ID/g). We observed that the bispecific tracers had prolonged blood retention, in which tracers with a longer linker tend to have a higher blood uptake and lower tumor uptake. Further investigations are needed to optimize the linker selection to generate promising bispecific PSMA/FAP-targeting tracers for prostate cancer imaging.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/90333
note: Citation: Verena, A.; Zhang, Z.; Kuo,H.-T.; Merkens, H.; Zeisler, J.; Wilson,R.; Bendre, S.; Wong, A.A.W.L.;Bénard, F.; Lin, K.-S. Synthesis andPreclinical Evaluation of Three Novel68Ga-Labeled BispecificPSMA/FAP-Targeting Tracers forProstate Cancer Imaging. Molecules2023, 28, 1088. https://doi.org/10.3390/molecules28031088Academic Editor: João D. G. CorreiaReceived: 24 December 2022Revised: 15 January 2023Accepted: 19 January 2023Published: 21 January 2023Copyright: © 2023 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).moleculesArticleSynthesis and Preclinical Evaluation of Three Novel68Ga-Labeled Bispecific PSMA/FAP-Targeting Tracers forProstate Cancer ImagingArsyangela Verena 1 , Zhengxing Zhang 1, Hsiou-Ting Kuo 1, Helen Merkens 1, Jutta Zeisler 1, Ryan Wilson 1,Shreya Bendre 1, Antonio A. W. L. Wong 1 , François Bénard 1,2,3,* and Kuo-Shyan Lin 1,2,3,*1 Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, BC V5Z1L3, Canada2 Department of Radiology, University of British Columbia, Vancouver, BC V5Z1M9, Canada3 Department of Functional Imaging, BC Cancer, Vancouver, BC V5Z4E6, Canada* Correspondence: fbenard@bccrc.ca (F.B.); klin@bccrc.ca (K.-S.L.); Tel.: +1-604-675-8208 (K.-S.L.)Abstract: Tumor heterogeneity limits the efficacy and reliability of monospecific radiopharmaceuticalsin prostate cancer diagnosis and therapy. To overcome this limitation and improve lesion detectionsensitivity, we developed and evaluated three bispecific radiotracers that can target both prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP), which are the two keyproteins overexpressed in prostate cancer. Three FAP-targeting ligands with various linker lengthswere synthesized through multistep organic synthesis, and then connected to the PSMA-targetingmotif. IC…
has type: Article
is shown at: 10.14288/1.0448032
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: Multidisciplinary Digital Publishing Institute
publisher DOI: 10.3390/molecules28031088
rights: CC BY 4.0
rights URI: https://creativecommons.org/licenses/by/4.0/
scholar level: Faculty
scholar level: Researcher
subject: prostate-specific membrane antigen
subject: fibroblast activation protein
subject: bispecific radiotracers
subject: PET/CT
subject: Gallium-68
type: Text
identifier URI: http://hdl.handle.net/2429/90333