Fibroblast-Activated Protein Inhibitor PET/CT: Cancer Diagnosis and Management

Fibroblast activation protein (FAP), overexpressed on cancer-associated fibroblasts (CAFs), is a novel target for molecular imaging of various tumors. Recently, the development of several small-molecule FAP inhibitors for radiolabeling with 68Ga has resulted in the emergence of studies evaluating its clinical role in cancer imaging. Preliminary findings have demonstrated that, in contrast to radiotracers taking advantage of cancer-specific targets such as PSMA and DOTATATE, FAPs as a target are the most promising that can compete with 18FDG in terms of widespread indications. They also have the potential to overcome the shortcomings of 18FDG, particularly false-positive uptake due to inflammatory or infectious processes, low sensitivity in certain cancer types, and radiotherapy planning. In addition, the attractive theranostic properties may facilitate the treatment of many refractory cancers. This review summarizes the current FAP variants and related clinical studies, focusing on radiopharmacy, dosimetry, and diagnostic and theranostic applications.

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68Ga-fibroblast activation protein inhibitor PET/CT on gross tumour volume delineation for radiotherapy planning of oesophageal cancer

Radiotherapy and Oncology ◽

10.1016/j.radonc.2021.02.015 ◽

2021 ◽

Author(s):

Liang Zhao ◽

Shanyu Chen ◽

Sijia Chen ◽

Yizhen Pang ◽

Yaqing Dai ◽

...

Keyword(s):

Oesophageal Cancer ◽

Tumour Volume ◽

Fibroblast Activation Protein ◽

Radiotherapy Planning ◽

Gross Tumour Volume ◽

Protein Inhibitor ◽

Fibroblast Activation ◽

Volume Delineation ◽

Pet Ct

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68Ga-Fibroblast Activation Protein Inhibitor, a Promising Radiopharmaceutical in PET/CT to Detect the Primary and Metastatic Lesions of Chromophobe Renal Cell Carcinoma

Clinical Nuclear Medicine ◽

10.1097/rlu.0000000000003454 ◽

2020 ◽

Vol 46 (2) ◽

pp. 177-179

Author(s):

Yizhen Pang ◽

Jihong Wei ◽

Qihang Shang ◽

Liang Zhao ◽

Haojun Chen

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Fibroblast Activation Protein ◽

Chromophobe Renal Cell Carcinoma ◽

Protein Inhibitor ◽

Fibroblast Activation ◽

Metastatic Lesions ◽

Pet Ct

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Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity – initial experience and comparison to [18F]FDG PET/CT and MRI

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05422-z ◽

2021 ◽

Author(s):

Christian Linz ◽

Roman C. Brands ◽

Olivia Kertels ◽

Alexander Dierks ◽

Joachim Brumberg ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Lymph Node ◽

Cell Carcinoma ◽

Squamous Cell ◽

Fdg Pet ◽

Cervical Lymph Node ◽

Fibroblast Activation Protein ◽

Cancer Associated Fibroblasts ◽

Pet Ct ◽

Fdg Pet Ct

Abstract Purpose While [18F]-fluorodeoxyglucose ([18F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT. Methods Ten consecutive, treatment-naïve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [18F]FDG and [68Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUVmax) and peak (SUVpeak) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference. Results [18F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([18F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3% vs. 87.5%; P = 0.32) and specificity (93.3% vs. 81.3%; P = 0.16) to [18F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples. Conclusion FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.

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PO-1777 68Ga-fibroblast activation protein inhibitor PET/CT on GTV delineation of oesophageal cancer

Radiotherapy and Oncology ◽

10.1016/s0167-8140(21)08228-1 ◽

2021 ◽

Vol 161 ◽

pp. S1503-S1504

Author(s):

L. Zhao ◽

H. Chen ◽

Q. Lin

Keyword(s):

Oesophageal Cancer ◽

Fibroblast Activation Protein ◽

Protein Inhibitor ◽

Fibroblast Activation ◽

Pet Ct

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Fibroblast Activation Protein Inhibitor PET/CT

Clinical Nuclear Medicine ◽

10.1097/rlu.0000000000003489 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Author(s):

Punit Sharma ◽

Shashank Shekhar Singh ◽

Shankaramurthy Gayana

Keyword(s):

Fibroblast Activation Protein ◽

Protein Inhibitor ◽

Fibroblast Activation ◽

Pet Ct

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Using 18F-flurodeoxyglucose and 68Ga-fibroblast activation protein inhibitor PET/CT to evaluate a new periprosthetic joint infection model of rabbit due to Staphylococcus aureus

Nuclear Medicine Communications ◽

10.1097/mnm.0000000000001495 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Yiqun Wang ◽

Honghong Liu ◽

Shulin Yao ◽

Zhiwei Guan ◽

Qingxiao Li ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Periprosthetic Joint Infection ◽

Joint Infection ◽

Fibroblast Activation Protein ◽

Infection Model ◽

Protein Inhibitor ◽

Fibroblast Activation ◽

Pet Ct

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Cancer-Associated Fibroblasts as Players in Cancer Development and Progression and Their Role in Targeted Radionuclide Imaging and Therapy

Cancers ◽

10.3390/cancers13051100 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1100

Author(s):

Sofia Koustoulidou ◽

Mark W. H. Hoorens ◽

Simone U. Dalm ◽

Shweta Mahajan ◽

Reno Debets ◽

...

Keyword(s):

Current Knowledge ◽

Tumour Microenvironment ◽

Therapeutic Interventions ◽

Great Promise ◽

Cancer Associated Fibroblasts ◽

Functional Heterogeneity ◽

Radioligand Therapy ◽

Targeted Interventions ◽

Theranostic Applications ◽

Complex Origin

Cancer Associated Fibroblasts (CAFs) form a major component of the tumour microenvironment, they have a complex origin and execute diverse functions in tumour development and progression. As such, CAFs constitute an attractive target for novel therapeutic interventions that will aid both diagnosis and treatment of various cancers. There are, however, a few limitations in reaching successful translation of CAF targeted interventions from bench to bedside. Several approaches targeting CAFs have been investigated so far and a few CAF-targeting tracers have successfully been developed and applied. This includes tracers targeting Fibroblast Activation Protein (FAP) on CAFs. A number of FAP-targeting tracers have shown great promise in the clinic. In this review, we summarize our current knowledge of the functional heterogeneity and biology of CAFs in cancer. Moreover, we highlight the latest developments towards theranostic applications that will help tumour characterization, radioligand therapy and staging in cancers with a distinct CAF population.

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Fibroblasts Influence the Efficacy, Resistance, and Future Use of Vaccines and Immunotherapy in Cancer Treatment

Vaccines ◽

10.3390/vaccines9060634 ◽

2021 ◽

Vol 9 (6) ◽

pp. 634

Author(s):

Bailee H. Sliker ◽

Paul M. Campbell

Keyword(s):

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Cell Types ◽

Fibroblast Activation Protein ◽

Cancer Associated Fibroblasts ◽

Cell Type ◽

Adaptive Immune ◽

Adaptive Immune Cells ◽

New Research ◽

Tumor Types

Tumors are composed of not only epithelial cells but also many other cell types that contribute to the tumor microenvironment (TME). Within this space, cancer-associated fibroblasts (CAFs) are a prominent cell type, and these cells are connected to an increase in tumor progression as well as alteration of the immune landscape present in and around the tumor. This is accomplished in part by their ability to alter the presence of both innate and adaptive immune cells as well as the release of various chemokines and cytokines, together leading to a more immunosuppressive TME. Furthermore, new research implicates CAFs as players in immunotherapy response in many different tumor types, typically by blunting their efficacy. Fibroblast activation protein (FAP) and transforming growth factor β (TGF-β), two major CAF proteins, are associated with the outcome of different immunotherapies and, additionally, have become new targets themselves for immune-based strategies directed at CAFs. This review will focus on CAFs and how they alter the immune landscape within tumors, how this affects response to current immunotherapy treatments, and how immune-based treatments are currently being harnessed to target the CAF population itself.

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