Abstract LBA032: Pan-cancer analysis of fibroblast activation protein alpha (FAP) expression to guide tumor selection for the peptide-targeted radionuclide therapy FAP-2286

Kwan, Tanya T.; Nguyen, Minh; Zboralski, Dirk; Schumann, Anne; Bredenbeck, Anne; Paschke, Matthias; Haase, C. G.; Hoehne, Aileen; Reineke, Ulrich; Smerling, Christiane; Osterkamp, Frank; Xiao, Jim; Simmons, Andrew; Harding, Thomas C.; Lin, Kevin L.

doi:10.1158/1535-7163.targ-21-lba032

Cited by 3 publications

(3 citation statements)

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“…More recently, clinical FAP-targeted PET imaging has been used to image lymphoma in addition to solid tumors [74]. Other FAP-targeting imaging agents such as (4-quinolinoyl)-glycyl-2-cyanopyrrolidine-based small molecules [75,76] and FAP-2286 [77] are also in development; however, they have not yet been as widely used as FAPI-04.…”

Section: Fap Targetingmentioning

confidence: 99%

Translating Molecules into Imaging—The Development of New PET Tracers for Patients with Melanoma

et al. 2022

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Melanoma is a deadly disease that often exhibits relentless progression and can have both early and late metastases. Recent advances in immunotherapy and targeted therapy have dramatically increased patient survival for patients with melanoma. Similar advances in molecular targeted PET imaging can identify molecular pathways that promote disease progression and therefore offer physiological information. Thus, they can be used to assess prognosis, tumor heterogeneity, and identify instances of treatment failure. Numerous agents tested preclinically and clinically demonstrate promising results with high tumor-to-background ratios in both primary and metastatic melanoma tumors. Here, we detail the development and testing of multiple molecular targeted PET-imaging agents, including agents for general oncological imaging and those specifically for PET imaging of melanoma. Of the numerous radiopharmaceuticals evaluated for this purpose, several have made it to clinical trials and showed promising results. Ultimately, these agents may become the standard of care for melanoma imaging if they are able to demonstrate micrometastatic disease and thus provide more accurate information for staging. Furthermore, these agents provide a more accurate way to monitor response to therapy. Patients will be able to receive treatment based on tumor uptake characteristics and may be able to be treated earlier for lesions that with traditional imaging would be subclinical, overall leading to improved outcomes for patients.

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Section: Fap Targetingmentioning

confidence: 99%

Translating Molecules into Imaging—The Development of New PET Tracers for Patients with Melanoma

et al. 2022

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“…Since FAP inhibitors (FAPIs) may be employed in nuclear medicine for PET imaging, the FAP-targeting SPECT probe is still inadequate in research. Consequently, the FAP-targeting SPECT probe must be developed promptly. − …”

Section: Introductionmentioning

confidence: 99%

Formulation and Preclinical Testing of Tc-99m-Labeled HYNIC-Glc-FAPT as a FAP-Targeting Tumor Radiotracer

Yang,

Li,

Ruan

et al. 2023

Bioconjugate Chem.

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Molecular imaging and targeted radiotherapy with radiolabeled fibroblast activation protein inhibitor (FAPI) targeting peptide probes hold great potential for enhancing the clinical management of patients with FAP-expressing cancers. However, the high cost of PET probes has prompted us to search for new FAP-targeting single-photon imaging agents. In this study, HYNIC-Glc-FAPT is synthesized and radiolabeled with technetium-99m using tricine/EDDA or dimer tricine as coligands to produce [99mTc]Tc-tricine/EDDA-HYNIC-Glc-FAPT and [99mTc]Tc-tricine(2)-HYNIC-Glc-FAPT. Both [99mTc]Tc-tricine/EDDA-HYNIC-Glc-FAPT and [99mTc]Tc-tricine(2)-HYNIC-Glc-FAPT were effectively synthesized with an excellent radiochemistry yield (both >97%, n = 6) in a single-step technique, and their stability in PBS and human serum was satisfactory. Compared to [99mTc]Tc-tricine(2)-HYNIC-Glc-FAPT, [99mTc]Tc-tricine/EDDA-HYNIC-Glc-FAPT exhibited a more hydrophilic nature with a log P of −3.53 ± 0.12. In vitro cellular uptake and blocking assays, internalization, efflux experiments, and affinity experiments all suggested a mechanism with high FAP-specificity and affinity. SPECT imaging and biodistribution of [99mTc]Tc-tricine/EDDA-HYNIC-Glc-FAPT demonstrated sustained high tumor uptake in BALB/c nude mice bearing U87MG tumors for 6 h. It demonstrated a long-range retention characteristic and more rapid clearance ability from nontarget organs. Collectively, we successfully synthesized [99mTc]Tc-tricine/EDDA-HYNIC-Glc-FAPT and [99mTc]Tc-tricine(2)-HYNIC-Glc-FAPT, and the excellent targeting properties of [99mTc]Tc-tricine/EDDA-HYNIC-Glc-FAPT suggest a potential diagnostic value in future clinical studies for advanced-stage FAP-expressing malignancies, especially in prognostic evaluation of tumors for it low price and convenient source.

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“…Nevertheless, throughout literature search, we find that comprehensive analysis of FAP based on big clinical data is still ill-established, and in-depth research of the relationship between FAP expression and tumor immunological profile is still lacking [ 11 – 13 ]. Thus, in this study, we systematically evaluated the FAP expression profile across thousands of cancer cases based on the TCGA, GTEx and CPTAC datasets, to establish the link between FAP expression and the clinical prognostic features.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of the oncogenic and immunological role of FAP and identification of the ceRNA network in human cancers

Mai

Liu

et al. 2023

Aging

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Fibroblast activation protein-alpha (FAP) is a transmembrane serine protease involving in tissue remodeling. Previous studies report that FAP is highly expressed in certain tumors and participated in oncogenesis. However, there is still lack of systematic and in-depth analysis of FAP based on clinical big data. Here, we comprehensively map the FAP expression profile, prognostic outcome, genetic alteration, immune infiltration across over 30 types of human cancers through multiple datasets including TCGA, CPTAC, and cBioPortal. We find that FAP is up-regulated in most cancer types, and increased FAP expression is associated with advanced pathological stages or poor prognosis in several cancers. Furthermore, FAP is significantly correlated with the infiltration of cancer-associated fibroblasts, macrophages, myeloid dendritic cells, as well as endothelia cells. Immunosuppressive checkpoint proteins or cytokines expression, microsatellite instability and tumor mutational burden analysis also indicate the regulation role of FAP in tumor progression. Gene enrichment analysis demonstrates that ECM-receptor interaction as well as extracellular matrix and structure process are linked to the potential mechanism of FAP in tumor pathogenesis. The ceRNA network is also constructed and identified the involvement of LINC00707/hsa-miR-30e-5p/FAP, LINC02535/hsa-miR-30e-5p/FAP, LINC02535/hsa-miR-30d-5p/FAP, as well as AC026356.1/hsa-miR-30d-5p/FAP axis in tumor progression. In conclusion, our study offers new insights into the oncogenic and immunological role of FAP from a pan-cancer perspective, providing new clues for developing novel targeted anti-tumor strategies.

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Abstract LBA032: Pan-cancer analysis of fibroblast activation protein alpha (FAP) expression to guide tumor selection for the peptide-targeted radionuclide therapy FAP-2286

Cited by 3 publications

References 0 publications

Translating Molecules into Imaging—The Development of New PET Tracers for Patients with Melanoma

Translating Molecules into Imaging—The Development of New PET Tracers for Patients with Melanoma

Formulation and Preclinical Testing of Tc-99m-Labeled HYNIC-Glc-FAPT as a FAP-Targeting Tumor Radiotracer

Comprehensive analysis of the oncogenic and immunological role of FAP and identification of the ceRNA network in human cancers

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