Visualization of fibroblast activation using 68Ga-FAPI PET/CT after pulmonary vein isolation with pulsed field compared with cryoballoon ablation.

BACKGROUND: Pulsed-field ablation (PFA) is a novel ablation modality for atrial fibrillation (AF) ablating myocardium by electroporation without tissue-heating. With its different mechanism of tissue ablation, it is assumed that lesion creation is divergent to thermal energy sources. 68Ga-fibroblast-activation protein inhibitor (FAPI) PET/CT targets FAP-alpha expressed by activated fibroblasts. We aimed to assess 68Ga-FAPI uptake in pulmonary veins as surrogate for ablation damage after PFA and cryoballoon ablation (CBA). METHODS: 26 patients (15 PFA, 11 CBA) underwent 68Ga-FAPI-PET/CT after ablation. Standardized uptake values (SUV) and fibroblast-activation volumes of localized tracer uptake were assessed. RESULTS: Patient characteristics were comparable between groups. In PFA, focal FAPI uptake was only observed in 3/15 (20%) patients, whereas in the CBA cohort, 10/11 (90.9%) patients showed atrial visual uptake. We observed lower values of SUVmax (2.85 ± 0.56 vs 4.71 ± 2.06, P = 0.025) and FAV (1.13 ± 0.84 cm3 vs 3.91 ± 2.74 cm3, P = 0.014) along with a trend towards lower SUVpeak and SUVmean in PFA vs CBA patients, respectively. CONCLUSION: Tissue response with respect to fibroblast activation seems to be less pronounced in PFA compared to established thermal ablation systems. This functional assessment might contribute to a better understanding of lesion formation in thermal and PFA ablation potentially contributing to better safety outcomes.

PSMA PET Tumor-to-Salivary Gland Ratio to Predict Response to [177Lu]PSMA Radioligand Therapy: An International Multicenter Retrospective Study.

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy can improve the outcome of patients with advanced metastatic castration-resistant prostate cancer, but patients do not respond uniformly. We hypothesized that using the salivary glands as a reference organ can enable selective patient stratification. We aimed to establish a PSMA PET tumor-to-salivary gland ratio (PSG score) to predict outcomes after [177Lu]PSMA. Methods: In total, 237 men with metastatic castration-resistant prostate cancer treated with [177Lu]PSMA were included. A quantitative PSG (qPSG) score (SUVmean ratio of whole-body tumor to parotid glands) was semiautomatically calculated on baseline [68Ga]PSMA-11 PET images. Patients were divided into 3 groups: high (qPSG > 1.5), intermediate (qPSG = 0.5-1.5), and low (qPSG < 0.5) scores. Ten readers interpreted the 3-dimensional maximum-intensity-projection baseline [68Ga]PSMA-11 PET images and classified patients into 3 groups based on visual PSG (vPSG) score: high (most of the lesions showed higher uptake than the parotid glands) intermediate (neither low nor high), and low (most of the lesions showed lower uptake than the parotid glands). Outcome data included a more than 50% prostate-specific antigen decline, prostate-specific antigen (PSA) progression-free survival, and overall survival (OS). Results: Of the 237 patients, the numbers in the high, intermediate, and low groups were 56 (23.6%), 163 (68.8%), and 18 (7.6%), respectively, for qPSG score and 106 (44.7%), 96 (40.5%), and 35 (14.8%), respectively, for vPSG score. The interreader reproducibility of the vPSG score was substantial (Fleiss weighted κ, 0.68). The more than 50% prostate-specific antigen decline was better in patients with a higher PSG score (high vs. intermediate vs. low, 69.6% vs. 38.7% vs. 16.7%, respectively, for qPSG [P < 0.001] and 63.2% vs 33.3% vs 16.1%, respectively, for vPSG [P < 0.001]). The median PSA progression-free survival of the high, intermediate, and low groups by qPSG score was 7.2, 4.0, and 1.9 mo (P < 0.001), respectively, by qPSG score and 6.7, 3.8, and 1.9 mo (P < 0.001), respectively, by vPSG score. The median OS of the high, intermediate, and low groups was 15.0, 11.2, and 13.9 mo (P = 0.017), respectively, by qPSG score and 14.3, 9.6, and 12.9 mo (P = 0.018), respectively, by vPSG score. Conclusion: The PSG score was prognostic for PSA response and OS after [177Lu]PSMA. The visual PSG score assessed on 3-dimensional maximum-intensity-projection PET images yielded substantial reproducibility and comparable prognostic value to the quantitative score.

Visualization of thermal damage using 68 Ga-FAPI-PET/CT after pulmonary vein isolation.

PURPOSE: 68 Ga-fibroblast-activation protein inhibitor (FAPI) positron emission tomography (PET) is a novel technique targeting FAP-alpha. This protein is expressed by activated fibroblasts which are the main contributors to tissue remodeling. The aim of this proof-of-concept study was to assess 68 Ga-FAPI uptake in the pulmonary vein (PV) region of the left atrium after pulmonary vein isolation (PVI) with cryoballoon ablation (CBA) and radiofrequency (RFA) as a surrogate for thermal damage. METHODS: Twelve PVI patients (5 RFA, 7 CBA) underwent 68 Ga-FAPI-PET 20.5 ± 12.8 days after PVI. Five patients without atrial fibrillation or previous ablation served as controls. Standardized uptake values of localized tracer uptake were calculated. RESULTS: Focal FAPI uptake around the PVs was observed in 10/12 (83.3%) PVI patients, no uptake was observed in 2 PVI patients and all controls. Patients after PVI had higher FAPI uptake in PVs compared to controls (SUVmax: 4.3 ± 2.2 vs. 1.6 ± 0.2, p < 0.01; SUVpeak: 2.9 ± 1.4 vs. 1.3 ± 0.2, p < 0.01). All CBA patients had an intense uptake, while in the RFA, group 2 (40%), 1 (20%), and 2 (40%) patients had an intense, moderate, and no uptake, respectively. We observed higher uptake values (SUVpeak) in CBA compared to RFA patients (4.4 ± 1.5 vs. 2.5 ± 0.8, p = 0.02). CONCLUSION: We demonstrate in-vivo visualization of 68 Ga-FAPI uptake as a surrogate for fibroblast activation after PVI. CBA seems to cause more pronounced fibroblast activation following tissue injury than RFA. Future studies are warranted to assess if this modality can contribute to a better understanding of the mechanisms of AF recurrence after PVI by lesion creation and gap assessment.