Abstract
Simple SummaryThe purpose of this systematic review is to summarize the findings of using fibroblast activation protein (FAP) as a new tracer for positron emission tomography (PET) in cancer patients. In the 19 included studies, FAP was evaluated in various cancers and showed promising initial results for staging as well as radiotherapy planning. Small molecules targeting fibroblast activation protein (FAP) have emerged as a new group of tracers for positron emission tomography (PET) in 2018. The purpose of this systematic review is therefore to summarize the evidence that has been gathered to date in patients and to discuss its possible implications for radiotherapy planning. The MEDLINE database was searched for the use of FAP-specific PET in cancer patients and the records were screened according to PRISMA guidelines. Nineteen studies were included. While dedicated analyses of FAP-specific PET for radiotherapy planning were available for glioblastoma, head and neck cancers, lung cancer, and tumors of the lower gastrointestinal tract, there is still very limited data for several epidemiologically significant cancers. In conclusion, FAP-specific PET represents a promising imaging modality for radiotherapy planning that warrants further research.
Highlights
positron emission tomography (PET)-computed tomography (CT) are nowadays recommended for a variety of clinical indications and have been shown to alter the management of oncology patients in many cases [2,3]
As fibroblast activation protein (FAP) is highly specific to a large subset of cancer-associated fibroblasts (CAFs), early molecules targeting FAP have initially been designed to inhibit FAP and to thereby serve as potential therapeutic agents before being used as a PET tracer in the past [5,6]
All articles that did not focus on the use of FAP-specific PET in cancer patients and did not provide information on the ability of FAP-specific PET to detect and delineate tumors were excluded
Summary
Target volume delineation has always been but has become increasingly challenging in radiation oncology given the ever more prevalent use of techniques that enable highly conformal radiotherapies such as intensity-modulated or stereotactic radiation therapy.As dose gradients become steeper, parts of the tumor which cannot be detected by pretreatment imaging may not be included and receive sufficient dose as the supposedly normal tissue in the vicinity of the tumor is spared.Developing new techniques to complement established imaging modalities such as computed tomography (CT) or magnetic resonance imaging (MRI) with or without contrast enhancement is of great importance not just from a diagnostic and a radiation oncology perspective.One modality which has provided continuous innovation and seen increasing use has been the positron emission tomography-computed tomography (PET-CT), mainly due to the development of new tracers in addition to the most prevalent 18 F-fluorodeoxyglucose (18 F-FDG) [1].PET-CTs are nowadays recommended for a variety of clinical indications and have been shown to alter the management of oncology patients in many cases [2,3].A novel group of tracers that has emerged recently are substances targeting the fibroblast activation protein (FAP) on the surface of fibroblasts in the tumor stroma, so-called cancer-associated fibroblasts (CAFs) first published in 2018 [4]. Target volume delineation has always been but has become increasingly challenging in radiation oncology given the ever more prevalent use of techniques that enable highly conformal radiotherapies such as intensity-modulated or stereotactic radiation therapy. Developing new techniques to complement established imaging modalities such as computed tomography (CT) or magnetic resonance imaging (MRI) with or without contrast enhancement is of great importance not just from a diagnostic and a radiation oncology perspective. One modality which has provided continuous innovation and seen increasing use has been the positron emission tomography-computed tomography (PET-CT), mainly due to the development of new tracers in addition to the most prevalent 18 F-fluorodeoxyglucose (18 F-FDG) [1]. Even though fibroblasts occur ubiquitously throughout the body, they normally express dipeptidyl peptidase 4 (DPP4) instead of the related FAP, which is why in preclinical in vitro and in vivo studies, FAP-specific tracers showed high specificity, affinity, and rapid internalization [4]
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