Cardiac fibroblast activation detected by Ga-68 FAPI PET imaging as a potential novel biomarker of cardiac injury/remodeling

Siebermair, Johannes; Köhler, Miriam; Kupusovic, Jana; Nekolla, Stephan G.; Kessler, Lukas; Ferdinandus, Justin; Guberina, Nika; Stuschke, Martin; Grafe, Hong; Siveke, Jens T.; Kochhäuser, Simon; Fendler, Wolfgang P.; Totzeck, Matthias; Wakili, Reza; Umutlu, Lale; Schlosser, Thomas; Rassaf, Tienush; Rischpler, Christoph

doi:10.1007/s12350-020-02307-w

Cited by 82 publications

(67 citation statements)

References 23 publications

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“…SSTR-directed PET was also shown to be superior over 67 Ga-scintigraphy for identification of muscle, lymph node, and uvea lesions in a study including 20 patients with sarcoidosis [15]. Subsequent pilot studies examining cardiac sarcoidosis confirmed superiority of SSTR-directed PET vs. 18 F-FDG PET as well as a close correlation of results from cardiac magnetic resonance imaging (CMR) and SSTR-directed PET/CT [16,17].…”

Section: Somatostatin Receptorsmentioning

confidence: 90%

“…Recently, Siebermair et al retrospectively analyzed 68 Ga-FAPI-PET images for cardiac tracer uptake of 32 patients that initially underwent PET analysis for tumor staging. The authors found an association with coronary artery disease (CAD), age, and left ventricle ejection fraction (LVEF) with FAPI uptake [67]. 68 Ga-FAPI in various inflammatory conditions.…”

Section: Fibroblast Activation Protein-α (Fap)mentioning

confidence: 99%

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Imaging Inflammation with Positron Emission Tomography

et al. 2021

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The impact of inflammation on the outcome of many medical conditions such as cardiovascular diseases, neurological disorders, infections, cancer, and autoimmune diseases has been widely acknowledged. However, in contrast to neurological, oncologic, and cardiovascular disorders, imaging plays a minor role in research and management of inflammation. Imaging can provide insights into individual and temporospatial biology and grade of inflammation which can be of diagnostic, therapeutic, and prognostic value. There is therefore an urgent need to evaluate and understand current approaches and potential applications for imaging of inflammation. This review discusses radiotracers for positron emission tomography (PET) that have been used to image inflammation in cardiovascular diseases and other inflammatory conditions with a special emphasis on radiotracers that have already been successfully applied in clinical settings.

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Section: Somatostatin Receptorsmentioning

confidence: 90%

Section: Fibroblast Activation Protein-α (Fap)mentioning

confidence: 99%

Imaging Inflammation with Positron Emission Tomography

et al. 2021

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“…Switching the radioisotope, following in the footsteps of prostate-speci c membrane antigen radiopharmaceuticals, could grant a better resolution, other than facilitating the commercial distribution of this tracer. [25]; it could serve as a biomarker, working in synergy with the well-established cardiovascular prognostic risk factors [29], and it might have a role to assess treatment-related cardiotoxicity [35]. In rheumatological studies, [ 68 Ga]Ga-FAPI proved to complement [ 18 F]FDG information targeting brosis and in ammation, respectively [24,26].…”

Section: Discussionmentioning

confidence: 99%

“…One study was designed as a phase I investigation [24]. In 12/23 studies [ 68 Ga]Ga-FAPI was offered as a compassionate drug according to the German Medicinal Product Act § 13(2b) [25,26,35,36,[27][28][29][30][31][32][33][34]. In the remaining 10/23 papers, the trial phase was not speci ed or designated as "not applicable" [37][38][39][40][41][42][43][44][45][46].…”

Section: Systematic Reviewmentioning

confidence: 99%

State-of-the-art of FAPI-PET Imaging: A Systematic Review and Meta-Analysis

Sollini

Kirienko

Gelardi

et al. 2021

Preprint

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Introduction Fibroblast Activation Protein-α (FAPα) is overexpressed on cancer-associated fibroblasts in approximately 90% of epithelial neoplasms, representing an appealing target for therapeutic and molecular imaging applications. [68Ga]Ga-labelled radiopharmaceuticals-FAP-inhibitors (FAPI) - have been developed for PET. We systematically reviewed and meta-analysed published literature to provide an overview of its clinical role.Materials and Methods The search, limited to January 1st, 2018 - March 31st 2021, was performed on MedLine and Embase databases using all the possible combinations of terms "FAP", FAPI", "PET/CT", "positron emission tomography", "fibroblast", “cancer-associated fibroblasts”, “CAF”, “molecular imaging”, and “fibroblast imaging”. Study quality was assessed using the QUADAS-2 criteria. Patient-based and lesion-based pooled sensitivities/specificities of FAPI PET were computed using a random-effects model directly from the STATA “metaprop” command. Between-study statistical heterogeneity was tested (I2-statistics).Results Twenty-three studies were selected for systematic review. Investigations on staging or restaging head and neck cancer (n=2, 29 patients), abdominal malignancies (n=6, 171 patients), various cancers (n=2, 143 patients), and radiation treatment planning (n=4, 56 patients) were included in the metanalysis. On patient-based analysis, pooled sensitivity was 0.99 (95% CI 0.97-1.00) with negligible heterogeneity; pooled specificity was 0.87 (95% CI 0.62-1.00), with negligible heterogeneity. On lesion-based analysis, sensitivity and specificity had high heterogeneity (I2=88.56% and I2=97.20%, respectively). Pooled sensitivity for the primary tumour was 1.00 (95% CI 0.98-1.00) with negligible heterogeneity. Pooled sensitivity/specificity of nodal metastases had high heterogeneity (I2=89.18% and I2=95.74%, respectively). Pooled sensitivity in distant metastases was good (0.93 with 95% CI 0.88-0.97) with negligible heterogeneity.Conclusions FAPI-PET appears promising, especially in imaging cancers unsuitable for [18F]FDG imaging, particularly primary lesions and distant metastases. However, high-level evidence is needed to define its’ role, specifically to identify cancer types, non-oncological diseases and clinical settings for its’ applications.

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“…7 Further retrospective evaluations of cardiac FAPI distribution in a heterogeneous patient population with metastasized cancer associated with preexisting coronary artery disease, cardiovascular risk factors or metabolic disease were reported. 8,9 However, 68 Ga-FAPI-04-PET investigations in patients after MI have not been reported yet. For this case presentation, we retrospectively evaluated fibroblast activation in a patient after MI und carcinoma patients without cardiac disease.…”

Section: Introductionmentioning

confidence: 99%

Imaging of cardiac fibroblast activation in a patient after acute myocardial infarction using 68Ga-FAPI-04

Notohamiprodjo

Nekolla

Robu

et al. 2022

Journal of Nuclear Cardiology

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Our previous study has demonstrated the feasibility of noninvasive imaging of fibroblast activation protein (FAP)-expression after myocardial infarction (MI) in MI-territory in a rat model with 68Ga-FAPI-04-PET. In the current extended clinical case, we sought to delineate cardiac uptake of 68Ga-FAPI-04 in a patient after MI with clinical indication for the evidence of fibroblast activation. Carcinoma patients without cardiac disease underwent 68Ga-FAPI-04-PET/CT as control. The patient with one-vessel disease underwent dynamic 68Ga-FAPI-04-cardiac-PET/CMR for 60 minutes. Correlation of cardiac 68Ga-FAPI-04 uptake with clinical findings, ECG, echocardiography, coronary-arteriography and enhanced cardiac-MRI with T1 MOLLI and ECV mapping were performed. No uptake was found in normal myocardium and in mature scar. A focal intense 68Ga-FAPI-04 uptake with continuous wash-out in the infarct territory of coronary occlusion correlating with T1 and ECV mapping was observed. The uptake of 68Ga-FAPI-04 extends beyond the actual infarcted area and overestimates the infarct size as confirmed by follow-up CMR.

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Cardiac fibroblast activation detected by Ga-68 FAPI PET imaging as a potential novel biomarker of cardiac injury/remodeling

Cited by 82 publications

References 23 publications

Imaging Inflammation with Positron Emission Tomography

Imaging Inflammation with Positron Emission Tomography

State-of-the-art of FAPI-PET Imaging: A Systematic Review and Meta-Analysis

Imaging of cardiac fibroblast activation in a patient after acute myocardial infarction using 68Ga-FAPI-04

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