In Vitro Evaluation of the Squaramide-Conjugated Fibroblast Activation Protein Inhibitor-Based Agents AAZTA5.SA.FAPi and DOTA.SA.FAPi

Moon, Euy Sung; Rymenant, Yentl Van; Battan, Sandeep; Loose, Joni De; Bracke, An; Veken, Pieter Van der; Meester, Ingrid De; Rösch, Frank

doi:10.3390/molecules26123482

Cited by 13 publications

(17 citation statements)

References 48 publications

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“…Several derivatives have shown promising clinical results, including FAPI-02 ( 16 ), FAPI-04 ( 17 ), FAPI-46 ( 18 ), FAPI-34 ( 19 ), FAPI-74 ( 20 ), DOTA.SA.FAPI and DATA5m.SA.FAPI ( 21 ), DOTA-2P(FAPI) 2 ( 22 ), and FAPI-42 ( 23 ). Many derivatives are being developed, and some promising preclinical data have been obtained, such as 18 F-fluoroglycosylation-FAPI ( 18 F-FGlc-FAPI) ( 24 ), QCP01 and QCP02 ( 25 ), and AAZTA5.SA.FAPI ( 26 ) ( Table 1 ).…”

Section: Targeting Cafs For Imagingmentioning

confidence: 99%

“…In clinical studies, 68 Ga-DATA5m.SA.FAPI PET/CT showed specific uptake in focal nodular hyperplasia in the liver ( 35 ), and there was no significant difference in tumor uptake between 68Ga-DOTA.SA.FAPI and 18 F-FDG compared with 18 F-FDG in 14 types of tumor imaging in a total of 54 patients, with the exception of brain metastatic lesions ( 27 ). Next, the team found that radiolabeling SA.FAPI with AAZTA5 as a chelator (i.e., AAZTA5.SA.FAPI) was superior to both DOTA and DATA5m in terms of labeling process and drug yield, and the IC 50 of the product was in the low nanomolar range (0.55–0.57 nM), but the drug is still in preclinical studies ( 26 ).…”

Section: Targeting Cafs For Imagingmentioning

confidence: 99%

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FAPI-PET/CT in Cancer Imaging: A Potential Novel Molecule of the Century

Huang

et al. 2022

Front. Oncol.

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Fibroblast activation protein (FAP), a type II transmembrane serine protease, is highly expressed in more than 90% of epithelial tumors and is closely associated with various tumor invasion, metastasis, and prognosis. Using FAP as a target, various FAP inhibitors (FAPIs) have been developed, most of which have nanomolar levels of FAP affinity and high selectivity and are used for positron emission tomography (PET) imaging of different tumors. We have conducted a systematic review of the available data; summarized the biological principles of FAPIs for PET imaging, the synthesis model, and metabolic characteristics of the radiotracer; and compared the respective values of FAPIs and the current mainstream tracer 18F-Fludeoxyglucose (18F-FDG) in the clinical management of tumor and non-tumor lesions. Available research evidence indicates that FAPIs are a molecular imaging tool complementary to 18F-FDG and are expected to be the new molecule of the century with better imaging effects than 18F-FDG in a variety of cancers, including gastrointestinal tumors, liver tumors, breast tumors, and nasopharyngeal carcinoma.

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Section: Targeting Cafs For Imagingmentioning

confidence: 99%

Section: Targeting Cafs For Imagingmentioning

confidence: 99%

FAPI-PET/CT in Cancer Imaging: A Potential Novel Molecule of the Century

Huang

et al. 2022

Front. Oncol.

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“…The same team also synthesized and studied the AAZTA 5 analogue of DATA 5m -SA-FAPi, following a strictly comparable synthesis sequence (Scheme 14) [84]. The broader coordination capabilities of AAZTA allowed 68 Ga, 44 Sc, and 177 Lu radiolabeling with direct comparison with DOTA-SA-FAPi.…”

Section: Fibroblast Activation Protein Inhibitorsmentioning

confidence: 99%

“…maceuticals 2022, 15, x FOR PEER REVIEW 21 of Scheme 14. Synthesis of AAZTA 5 -and DATA 5m -SA-FAPi derivatives [82,84].…”

Section: Fibroblast Activation Protein Inhibitorsmentioning

confidence: 99%

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AAZTA-Derived Chelators for the Design of Innovative Radiopharmaceuticals with Theranostic Applications

et al. 2022

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With the development of 68Ga and 177Lu radiochemistry, theranostic approaches in modern nuclear medicine enabling patient-centered personalized medicine applications have been growing in the last decade. In conjunction with the search for new relevant molecular targets, the design of innovative chelating agents to easily form stable complexes with various radiometals for theranostic applications has gained evident momentum. Initially conceived for magnetic resonance imaging applications, the chelating agent AAZTA features a mesocyclic seven-membered diazepane ring, conferring some of the properties of both acyclic and macrocyclic chelating agents. Described in the early 2000s, AAZTA and its derivatives exhibited interesting properties once complexed with metals and radiometals, combining a fast kinetic of formation with a slow kinetic of dissociation. Importantly, the extremely short coordination reaction times allowed by AAZTA derivatives were particularly suitable for short half-life radioelements (i.e., 68Ga). In view of these particular characteristics, the scope of this review is to provide a survey on the design, synthesis, and applications in the nuclear medicine/radiopharmacy field of AAZTA-derived chelators.

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Translational assessment of a DATA-functionalized FAP inhibitor with facile 68Ga-labeling at room temperature

Escudero-Castellanos

Kurth

Imlimthan

et al. 2023

Eur J Nucl Med Mol Imaging

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Purpose The present study aims at evaluating the preclinical and the clinical performance of [68Ga]Ga-DATA5m.SA.FAPi, which has the advantage to be labeled with gallium-68 at room temperature. Methods [68Ga]Ga-DATA5m.SA.FAPi was assessed in vitro on FAP-expressing stromal cells, followed by biodistribution and in vivo imaging on prostate and glioblastoma xenografts. Moreover, the clinical assessment of [68Ga]Ga-DATA5m.SA.FAPi was conducted on six patients with prostate cancer, aiming on investigating, biodistribution, biokinetics, and determining tumor uptake. Results [68Ga]Ga-DATA5m.SA.FAPi is quantitatively prepared in an instant kit-type version at room temperature. It demonstrated high stability in human serum, affinity for FAP in the low nanomolar range, and high internalization rate when associated with CAFs. Biodistribution and PET studies in prostate and glioblastoma xenografts revealed high and specific tumor uptake. Elimination of the radiotracer mainly occurred through the urinary tract. The clinical data are in accordance with the preclinical data concerning the organ receiving the highest absorbed dose (urinary bladder wall, heart wall, spleen, and kidneys). Different to the small-animal data, uptake of [68Ga]Ga-DATA5m.SA.FAPi in tumor lesions is rapid and stable and tumor-to-organ and tumor-to-blood uptake ratios are high. Conclusion The radiochemical, preclinical, and clinical data obtained in this study strongly support further development of [68Ga]Ga-DATA5m.SA.FAPi as a diagnostic tool for FAP imaging.

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In Vitro Evaluation of the Squaramide-Conjugated Fibroblast Activation Protein Inhibitor-Based Agents AAZTA5.SA.FAPi and DOTA.SA.FAPi

Cited by 13 publications

References 48 publications

FAPI-PET/CT in Cancer Imaging: A Potential Novel Molecule of the Century

FAPI-PET/CT in Cancer Imaging: A Potential Novel Molecule of the Century

AAZTA-Derived Chelators for the Design of Innovative Radiopharmaceuticals with Theranostic Applications

Translational assessment of a DATA-functionalized FAP inhibitor with facile 68Ga-labeling at room temperature

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