Clinical summary of fibroblast activation protein inhibitor-based radiopharmaceuticals: cancer and beyond

Li, Mengting; Younis, Muhsin H.; Zhang, Yongxue; Cai, Weibo; Lan, Xiaoli

doi:10.1007/s00259-022-05706-y

Cited by 60 publications

(44 citation statements)

References 184 publications

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“…Since fibroblast activation can remodel the tissue in fibrosis, inflammation and tissue healing, this may lead to tracer uptake in non-cancerous tissue. It is also worth noting that FAPI tracers have also been studied in non-oncologic diseases, such as IgG4-related disease [ 50 ], cardiac amyloidosis [ 51 , 52 , 53 ], risk of sudden cardiac death [ 54 ], tuberculosis [ 55 ], Crohn’s disease [ 56 ], Erdheim–Chester disease [ 57 ], arthritis and fibrosis. A slight uptake is also seen in the thyroid that may increase in cases of chronic thyroiditis and immune related thyroiditis [ 58 , 59 ].…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Activation Protein Inhibitor (FAPI)-Based Theranostics—Where We Are at and Where We Are Heading: A Systematic Review

Sidrak

Feo

Corica

et al. 2023

IJMS

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Cancer is the leading cause of death around the globe, followed by heart disease and stroke, with the highest mortality to this day. We have reached great levels of understanding of how these various types of cancer operate at a cellular level and this has brought us to what we call “precision medicine” where every diagnostic examination and the therapeutic procedure is tailored to the patient. FAPI is among the new tracers that can be used to assess and treat many types of cancer. The aim of this review was to gather all the known literature on FAPI theranostics. A MEDLINE search was conducted on four web libraries, PUBMED, Cochrane, Scopus, and Web of Sciences. All of the available articles that included both diagnoses and therapy with FAPI tracers were collected and put through the CASP (Critical Appraisal Skills Programme) questionnaire for systematic reviewing. A total of 8 records were deemed suitable for CASP review, ranging from 2018 to November 2022. These studies were put through the CASP diagnostic checklist, in order to assess the goal of the study, diagnostic and reference tests, results, descriptions of the patient sample, and future applications. Sample sizes were heterogeneous, both for size as well as for tumor type. Only one author studied a single type of cancer with FAPI tracers. Progression of disease was the most common outcome, and no relevant collateral effects were noted. Although FAPI theranostics is still in its infancy and lacks solid grounds to be brought into clinical practice, it does not show any collateral effects that prohibit administration to patients, thus far, and has good tolerability profiles.

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Section: Discussionmentioning

confidence: 99%

Fibroblast Activation Protein Inhibitor (FAPI)-Based Theranostics—Where We Are at and Where We Are Heading: A Systematic Review

Sidrak

Feo

Corica

et al. 2023

IJMS

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“…With FAPI-specific PET imaging, patients do not require dietary preparation, and high-quality images can be obtained soon after tracer injection (10 min to 1 h, mainly 1 h) [ 21 ]. The superior value of [ 68 Ga]Ga-FAPI PET/CT over [ 18 F]FDG in detecting primary and metastatic lesions in digestive system cancers has been confirmed, most lesions showing higher tracer uptake with FAPI imaging, and it exhibits a promising role in the diagnosis, (re)staging, management, and treatment planning of digestive system cancers [ 22 ]. However, limited data about 99m Tc-labelled FAPIs in clinical have been reported, with only application in two patients (ovarian and pancreatic cancer) [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

The role of [99mTc]Tc-HFAPi SPECT/CT in patients with malignancies of digestive system: first clinical experience

Jia

et al. 2022

Eur J Nucl Med Mol Imaging

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Background Recently, PET/CT imaging with radiolabelled FAP inhibitors (FAPIs) has been widely evaluated in diverse diseases. However, rare report has been published using SPECT/CT, a more available imaging method, with [99mTc]Tc-labelled FAPI. In this study, we evaluated the potential effect of [99mTc]Tc-HFAPi in clinical analysis for digestive system tumours. Methods This is a single-centre prospective diagnostic efficiency study (Ethic approved No.: XJTU1AF2021LSK-021 of the First Affiliated Hospital of Xi’an Jiaotong University and ChiCTR2100048093 of the Chinese Clinical Trial Register). Forty patients with suspected or confirmed digestive system tumours underwent [99mTc]Tc-HFAPi SPECT/CT between January and June 2021. For dynamic biodistribution and dosimetry estimation, whole-body planar scintigraphy was performed at 10, 30, 90, 150, and 240 min post-injection in four representative patients. Optimal acquisition time was considered in all the patients at 60–90 min post-injection, then quantified or semi-quantified using SUVmax and T/B ratio was done. The diagnostic performance of [99mTc]Tc-HFAPi was calculated and compared with those of contrast-enhanced CT (ceCT) using McNemar test, and the changes of tumour stage and oncologic management were recorded. Results Physiological distribution of [99mTc]Tc-HFAPi was observed in the liver, pancreas, gallbladder, and to a lesser extent in the kidneys, spleen and thyroid. Totally, 40 patients with 115 lesions were analysed. The diagnostic sensitivity of [99mTc]Tc-HFAPi for non-operative primary lesions was similar to that of ceCT (94.29% [33/35] vs 100% [35/35], respectively; P = 0.5); in local relapse detection, [99mTc]Tc-HFAPi was successfully detected in 100% (n = 3) of patients. In the diagnosis of suspected metastatic lesions, [99mTc]Tc-HFAPi exhibited higher sensitivity (89.66% [26/29] vs 68.97% [20/29], respectively, P = 0.03) and specificity (97.9% [47/48] vs 85.4% [41/48], respectively, P = 0.03) than ceCT, especially with 100% (24/24) specificity in the diagnosis of liver metastases, resulting in 20.0% (8/40) changes in TNM stage and 15.0% (6/40) changes in oncologic management. Conclusion [99mTc]Tc-HFAPi demonstrates a greater diagnostic efficiency than ceCT in the detection of distant metastasis, especially in identifying liver metastases.

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“…Fibroblast activation, migration, and proliferation in the intima have been reported as one of the causes of intimal hyperplasia ( 50 ). Currently, the targeted imaging of fibroblast activation protein alpha (FAP), a serine protease expressed mainly by activated fibroblast, is gaining tremendous interest in cancer and inflammatory diseases ( 355 ). The interest in FAP targeted imaging started with the development of radiolabeled FAP inhibitor [ 125 I]MIP-1232 for single-photon emission computed tomography (SPECT) imaging of atherosclerosis ( 356 ).…”

Section: Potential Novel Pet Tracers For Diagnosis and Monitoring Of ...mentioning

confidence: 99%

“…From these FAPI based radiotracers, [ 68 Ga]FAPI-04 has been rapidly implemented in clinical trials and has shown superiority compared to the long-time gold standard [ 18 F]FDG for imaging cancer and inflammation as recently summarized by Li et al ( 355 ). These reports showed high and specific uptake in tumors as well as at sites of fibrosis and inflammation while displaying negligible blood pool and brain radioactivity supporting its potential application for imaging both C-GCA and LV-GCA.…”

Section: Potential Novel Pet Tracers For Diagnosis and Monitoring Of ...mentioning

confidence: 99%

Novel PET Imaging of Inflammatory Targets and Cells for the Diagnosis and Monitoring of Giant Cell Arteritis and Polymyalgia Rheumatica

et al. 2022

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Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two interrelated inflammatory diseases affecting patients above 50 years of age. Patients with GCA suffer from granulomatous inflammation of medium- to large-sized arteries. This inflammation can lead to severe ischemic complications (e.g., irreversible vision loss and stroke) and aneurysm-related complications (such as aortic dissection). On the other hand, patients suffering from PMR present with proximal stiffness and pain due to inflammation of the shoulder and pelvic girdles. PMR is observed in 40–60% of patients with GCA, while up to 21% of patients suffering from PMR are also affected by GCA. Due to the risk of ischemic complications, GCA has to be promptly treated upon clinical suspicion. The treatment of both GCA and PMR still heavily relies on glucocorticoids (GCs), although novel targeted therapies are emerging. Imaging has a central position in the diagnosis of GCA and PMR. While [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) has proven to be a valuable tool for diagnosis of GCA and PMR, it possesses major drawbacks such as unspecific uptake in cells with high glucose metabolism, high background activity in several non-target organs and a decrease of diagnostic accuracy already after a short course of GC treatment. In recent years, our understanding of the immunopathogenesis of GCA and, to some extent, PMR has advanced. In this review, we summarize the current knowledge on the cellular heterogeneity in the immunopathology of GCA/PMR and discuss how recent advances in specific tissue infiltrating leukocyte and stromal cell profiles may be exploited as a source of novel targets for imaging. Finally, we discuss prospective novel PET radiotracers that may be useful for the diagnosis and treatment monitoring in GCA and PMR.

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Clinical summary of fibroblast activation protein inhibitor-based radiopharmaceuticals: cancer and beyond

Cited by 60 publications

References 184 publications

Fibroblast Activation Protein Inhibitor (FAPI)-Based Theranostics—Where We Are at and Where We Are Heading: A Systematic Review

Fibroblast Activation Protein Inhibitor (FAPI)-Based Theranostics—Where We Are at and Where We Are Heading: A Systematic Review

The role of [99mTc]Tc-HFAPi SPECT/CT in patients with malignancies of digestive system: first clinical experience

Novel PET Imaging of Inflammatory Targets and Cells for the Diagnosis and Monitoring of Giant Cell Arteritis and Polymyalgia Rheumatica

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