scholarly journals Radioligands Targeting Fibroblast Activation Protein (FAP)

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5744
Author(s):  
Thomas Lindner ◽  
Frederik L. Giesel ◽  
Clemens Kratochwil ◽  
Sebastian E. Serfling
Keyword(s):  
Nuclear Medicine ◽  
Fibroblast Activation Protein ◽  
Pharmaceutical Companies ◽  
Radioligand Therapy ◽  
Comprehensive Overview ◽  
Fibroblast Activation ◽  
Dietary Restrictions ◽  
18F Fdg ◽  
Medicine Community ◽  
Significant Attention

Targeting fibroblast activation protein (FAP) in cancer-associated fibroblasts (CAFs) has attracted significant attention in nuclear medicine. Since these cells are present in most cancerous tissues and FAP is rarely expressed in healthy tissues, anti-FAP tracers have a potential as pan-tumor agents. Compared to the standard tumor tracer [18F]FDG, these tracers show better tumor-to-background ratios (TBR) in many indications. Unlike [18F]FDG, FAP-targeted tracers do not require exhausting preparations, such as dietary restrictions on the part of the patient, and offer the possibility of radioligand therapy (RLT) in a theragnostic approach. Although a radiolabeled antibody was clinically investigated as early as the 1990s, the breakthrough event for FAP-targeting in nuclear medicine was the introduction and clinical application of the so-called FAPI-tracers in 2018. From then, the development and application of FAP-targeted tracers became hot topics for the radiopharmaceutical and nuclear medicine community, and attracted the interest of pharmaceutical companies. The aim of this review is to provide a comprehensive overview of the development of FAP-targeted radiopharmaceuticals and their application in nuclear medicine.

scholarly journals Clinical Translational Evaluation of Al18F-NOTA-FAPI for Fibroblast Activation Protein Targeted Tumour Imaging

2021 ◽  
Author(s):  
Shuailiang Wang ◽  
Xin Zhou ◽  
Xiaoxia Xu ◽  
Jin Ding ◽  
Song Liu ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Fibroblast Activation Protein ◽  
Ct Imaging ◽  
Whole Body ◽  
Tumour Imaging ◽  
Tumour Detection ◽  
Fibroblast Activation ◽  
Tumour Bearing ◽  
Pet Ct ◽  
18F Fdg

Abstract PurposeIn this study, a novel Al18F-NOTA-FAPI probe was developed for fibroblast activation protein (FAP) targeted tumour imaging, which was available to achieve curie level radioactivity by automatic synthesizer. The tumour detection efficacy of Al18F-NOTA-FAPI was further validated both in preclinical and clinical translational studies. MethodsThe radiolabeling procedure of Al18F-NOTA-FAPI was optimized. Cell uptake and competitive binding assay were completed with U87MG and A549 cell lines, to evaluate the affinity and specificity of Al18F-NOTA-FAPI probe. The biodistribution, pharmacokinetics, radiation dosimetry and tumour imaging efficacy of Al18F-NOTA-FAPI probe were researched with healthy Kunming (KM) and/or U87MG model mice. After the approval of ethical committee, Al18F-NOTA-FAPI probe was translated into clinical for the PET/CT imaging of first 10 cancer patients. ResultsThe radiolabeling yield of Al18F-NOTA-FAPI was 33.8 ± 3.2% through manually operation (n = 10), with the radiochemical purity over than 99% and the specific activity of 9.3-55.5 MBq/nmol. Whole body effective dose of Al18F-NOTA-FAPI was estimated to be 1.24E-02 mSv/MBq, lower than several other FAPI probes ( 68Ga-FAPI-04, 68Ga-FAPI-46 and 68Ga-FAPI-74). In U87MG tumour bearing mice, Al18F-NOTA-FAPI showed good tumor detection efficacy from the results of micro PET/CT imaging and biodistribution studies. In organ biodistribution study of human patients, Al18F-NOTA-FAPI showed lower SUVmean than 2-[18F]FDG in most organs, especially in liver (1.1 ± 0.2 vs. 2.0 ± 0.9), brain (0.1 ± 0.0 vs. 5.9 ± 1.3), and bone marrow (0.9 ± 0.1 vs. 1.7 ± 0.4). Meanwhile, Al18F-NOTA-FAPI do not show extensive bone uptakes, and was able to find out more tumour lesions than 2-[18F]FDG in the PET/CT imaging of several patients. ConclusionAl18F-NOTA-FAPI probe was successfully fabricated and applied in fibroblast activation protein targeted tumour PET/CT imaging, which showed excellent imaging quality and tumour detection efficacy in U87MG tumour bearing mice as well as in human cancer patients.

scholarly journals Potential Targets Other than PSMA for Prostate Cancer Theranostics: A Systematic Review

2021 ◽  
Vol 10 (21) ◽  
pp. 4909
Author(s):  
Mathieu Gauthé ◽  
Paul Sargos ◽  
Eric Barret ◽  
Gaëlle Fromont-Hankard ◽  
Jean-Baptiste Beauval ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Nuclear Medicine ◽  
Web Search ◽  
Somatostatin Receptors ◽  
Fibroblast Activation Protein ◽  
Low Grade ◽  
Fibroblast Activation ◽  
Time Restrictions ◽  
Surface Receptor ◽  
Cancer Theranostics

Background: Prostate-specific membrane antigen (PSMA) is not sufficiently overexpressed in a small proportion of prostate cancer (PCa) patients, who require other strategies for imaging and/or treatment. We reviewed potential targets other than PSMA for PCa theranostics in nuclear medicine that have already been tested in humans. Methods: We performed a systematic web search in the PubMed and Cochrane databases, with no time restrictions by pooling terms (“prostate cancer”, “prostatic neoplasms”) and (“radioligand”, “radiotracer”). Included articles were clinical studies. The results were synthetized by the target type. Results: We included 38 studies on six different targets: gastrin-releasing peptide receptors (GRPRs) (n = 23), androgen receptor (n = 11), somatostatin receptors (n = 6), urokinase plasminogen activator surface receptor (n = 4), fibroblast activation protein (n = 2 studies) and integrin receptors (n = 1). GRPRs, the most studied target, has a lower expression in high-grade PCa, CRPC and bone metastases. Its use might be of higher interest in treating earlier stages of PCa or low-grade PCa. Radiolabeled fibroblast activation protein inhibitors were the most recent and promising molecules, but specific studies reporting their interest in PCa are needed. Conclusion: Theranostics in nuclear medicine will continue to develop in the future, especially for PCa patients. Targets other than PSMA exist and deserve to be promoted.

Fibroblast activation protein inhibitor (FAPi) positive tumour fraction on PET/CT correlates with Ki-67 in liver metastases of neuroendocrine tumours

2021 ◽  
Author(s):  
Barbara Kreppel ◽  
Maria Angeles Gonzalez-Carmona ◽  
Georg Feldmann ◽  
Jim Küppers ◽  
Euy Sung Moon ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Prognostic Significance ◽  
Correlation Coefficients ◽  
Clinical Parameter ◽  
Fibroblast Activation Protein ◽  
Ki 67 ◽  
Fibroblast Activation ◽  
Positron Emission ◽  
Pet Ct ◽  
18F Fdg

Abstract Aim Gallium-68-labelled inhibitors of the fibroblast activation protein (FAPi) enable positron emission tomography/computed tomography (PET/CT) imaging of fibroblast activation. We evaluated if [68Ga]Ga-DATA5 m.SA.FAPi PET/CT is related to Ki-67 as a marker of tumour aggressiveness in patients with liver metastases of NET. Methods Thirteen patients with liver metastases of a histologically confirmed NET who underwent PET/CT with [68Ga]Ga-DATA5 m.SA.FAPi, [18F]FDG and [68Ga]Ga-DOTA-TOC were retrospectively analyzed. PET-positive liver tumour volumes were segmented for calculation of volume, SUVmax and PET-positive tumour fraction (TF). PET parameters were correlated with Ki-67. Results FDGSUVmax correlated positively (rho = 0.543, p < 0.05) and DOTATOCSUVmax correlated negatively (rho = –0.618, p < 0.05) with Ki-67, the correlation coefficients were in the moderate range. There was no significant correlation between FAPiSUVmax and Ki-67 (rho = 0.382, p > 0.05). FAPiTF correlated positively (rho = 0.770, p < 0.01) and DOTATOCTF correlated negatively (rho = –0.828, p < 0.01) with Ki-67, both significantly with high correlation coefficients. FDGTF also correlated significantly with Ki-67, with a moderate correlation coefficient (rho = 0.524, p < 0.05). The ratio FAPiVOL:DOTATOCVOL showed a significant and strong correlation with Ki-67 (rho = 0.808, p < 0.01). Conclusion The ratio FAPiVOL:DOTATOCVOL might serve as a clinical parameter for the assessment of dedifferentiation and aggressiveness of liver metastases in patients with NET. [68Ga]Ga-DATA5 m.SA.FAPi might hold potential for identification of high-risk patients. Further studies are warranted to evaluate its prognostic significance in comparison to [18F]FDG in patients with NET.

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