Fibroblast activation protein-based theranostics in cancer research: A state-of-the-art review

Zhao, Liang; Chen, Jianhao; Pang, Yizhen; Fu, Kang; Shang, Qihang; Wu, Hua; Sun, Long; Qi, Lin; Chen, Haojun

doi:10.7150/thno.69475

Cited by 102 publications

(91 citation statements)

References 86 publications

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“…Cancer-associated fibroblasts (CAFs) are abundant components of the stroma in solid tumors. Therefore, targeting CAFs could be an indirect and promising approach for cancer diagnosis and therapy …”

Section: Introductionmentioning

confidence: 99%

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Development of Fibroblast Activation Protein Inhibitor-Based Dimeric Radiotracers with Improved Tumor Retention and Antitumor Efficacy

et al. 2022

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Fibroblast activation protein (FAP), a fundamental component of the tumor stroma, is overexpressed in cancerassociated fibroblasts (CAFs). As a promising theranostic probe, we evaluated whether the FAP inhibitor (FAPI) dimer (DOTA-2P [FAPI] 2 ) is more effective than its monomeric analogs for FAP-targeted radionuclide therapy. [ 68 Ga]Ga/[ 177 Lu]Lu-DOTA-2P(FAPI) 2 were assayed in a stability study, small-animal positron emission tomography (PET) and single-photon emission computed tomography (SPECT), biodistribution, and radionuclide therapy to comprehensively evaluate their preclinical pharmacokinetics. The pharmacokinetics of [ 68 Ga]Ga-DOTA-2P(FAPI) 2 and [ 177 Lu]Lu-DOTA-2P(FAPI) 2 were determined in FAP-positive hepatocellular carcinoma patient-derived xenografts (PDXs) and HT-1080-FAP cell-derived xenografts (CDXs).[ 68 Ga]Ga-DOTA-2P(FAPI) 2 and [ 177 Lu]Lu-DOTA-2P(FAPI) 2 were stable in phosphate-buffered saline for 4 h. The tumor retention of [ 68 Ga]Ga-DOTA-2P(FAPI) 2 was better than that of [ 68 Ga]Ga-FAPI-46 in HT-1080-FAP CDXs, while healthy organs showed low tracer uptake and fast body clearance. In single-photon emission computed tomography, [ 177 Lu]Lu-DOTA-2P(FAPI) 2 showed a higher uptake and longer retention for tumors in both PDXs and CDXs from 1−48 h. [ 177 Lu]Lu-DOTA-2P(FAPI) 2 showed the best inhibition of tumor growth in PDXs and CDXs. DOTA-2P(FAPI) 2 has increased tumor uptake and retention properties compared to FAPI-46, which significantly improves the use of FAPI-based vectors for PET imaging and radionuclide therapy. [ 177 Lu]Lu-DOTA-2P(FAPI) 2 may be safe and effective for the treatment of FAP-positive malignant tumors.

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Section: Introductionmentioning

confidence: 99%

“…Therefore, targeting CAFs could be an indirect and promising approach for cancer diagnosis and therapy. 5 Fibroblast activation protein (FAP), a type II integral membrane glycoprotein, is overexpressed in CAFs and expressed at low levels in healthy tissues. Thus, FAP may be a representative target of CAFs.…”

Section: Introductionmentioning

confidence: 99%

Development of Fibroblast Activation Protein Inhibitor-Based Dimeric Radiotracers with Improved Tumor Retention and Antitumor Efficacy

et al. 2022

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“…Many studies suggested that meningioma can cause increased uptake of various radiotracers, including 18 F-FDG, 3 68 Ga-DOTATATE, 8 68 Ga-PSMA, 9 18 F-FLT, 10 18 F-florapronol, 11 and so on. 68 Ga-labeled FAPI has recently been introduced as a promising tumor imaging agent, which has shown promising results in the diagnosis of cancer and inflammatory diseases 12–14 . In this case, benign intraosseous meningioma can cause increased FAPI activity, which needs our greater awareness.…”

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confidence: 99%

Elevated 68Ga-FAPI Uptake by Primary Benign Intraosseous Meningioma

Gong

Xiao

et al. 2022

Clin Nucl Med

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Intraosseous meningioma is an extremely rare benign tumor. We present the 68Ga–fibroblast activation protein inhibitor (FAPI) PET/CT findings of primary intraosseous meningioma in a 71-year-old woman. 68Ga-FAPI PET/CT revealed an intraosseous mass in the right parietal bone with increased FAPI activity. Primary skull malignancy was suspected. However, pathological examination after resection of the mass in the right parietal bone confirmed the diagnosis of benign meningioma (WHO I). A final diagnosis of benign intraosseous meningioma was made.

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“…Upon certain stimuli, the fibroblast inside tumor stroma becomes “activated” ( 113 ). Accordingly, fibroblasts acquire different morphology and expression profiles ( 114 ). These CAFs produce growth factors that promote tumor growth, angiogenesis, and the recruitment of protumorigenic inflammatory cells.…”

Section: Mechanism Of Resistance To Chemotherapeuticsmentioning

confidence: 99%

Extracellular Vesicles and Resistance to Anticancer Drugs: A Tumor Skeleton Key for Unhinging Chemotherapies

et al. 2022

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Although surgical procedures and clinical care allow reaching high success in fighting most tumors, cancer is still a formidable foe. Recurrence and metastatization dampen the patients’ overall survival after the first diagnosis; nevertheless, the large knowledge of the molecular bases drives these aspects. Chemoresistance is tightly linked to these features and is mainly responsible for the failure of cancer eradication, leaving patients without a crucial medical strategy. Many pathways have been elucidated to trigger insensitiveness to drugs, generally associated with the promotion of tumor growth, aggressiveness, and metastatisation. The main mechanisms reported are the expression of transporter proteins, the induction or mutations of oncogenes and transcription factors, the alteration in genomic or mitochondrial DNA, the triggering of autophagy or epithelial-to-mesenchymal transition, the acquisition of a stem phenotype, and the activation of tumor microenvironment cells. Extracellular vesicles (EVs) can directly transfer or epigenetically induce to a target cell the molecular machinery responsible for the acquisition of resistance to drugs. In this review, we resume the main body of knowledge supporting the crucial role of EVs in the context of chemoresistance, with a particular emphasis on the mechanisms related to some of the main drugs used to fight cancer.

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Fibroblast activation protein-based theranostics in cancer research: A state-of-the-art review

Cited by 102 publications

References 86 publications

Development of Fibroblast Activation Protein Inhibitor-Based Dimeric Radiotracers with Improved Tumor Retention and Antitumor Efficacy

Development of Fibroblast Activation Protein Inhibitor-Based Dimeric Radiotracers with Improved Tumor Retention and Antitumor Efficacy

Elevated 68Ga-FAPI Uptake by Primary Benign Intraosseous Meningioma

Extracellular Vesicles and Resistance to Anticancer Drugs: A Tumor Skeleton Key for Unhinging Chemotherapies

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