European Journal of Nuclear Medicine and Molecular Imaging最新文献

Background: Aortic stenosis (AS) induces myocardial remodeling and fibroblast activation, yet modifiable biomarkers capable of capturing active fibrogenesis and predicting post-transcatheter aortic valve implantation (TAVI) recovery are currently scarce. Fibroblast activation protein (FAP)-targeted PET serves as a noninvasive tool to visualize activated fibroblasts in vivo. We evaluated a time-robust, blood-pool-normalized myocardial [⁶⁸Ga]Ga-FAPI PET imaging biomarker that reflects AS burden and predicts outcomes after TAVI.

Methods: Nineteen patients with severe symptomatic AS underwent [⁶⁸Ga]Ga-FAPI-04 PET/CT at 60, 70, and 120 min. Using an in-house semi-automatic pipeline, the left ventricular (LV) myocardium was segmented, and regions of elevated fibroblast activity (EFM) were delineated using a blood-pool-anchored, time-point-specific threshold. We quantified myocardial SUV_mean, blood-pool SUV_mean, and a normalized myocardium-to-blood index, TBR(EFM), and assessed associations with N-terminal pro-brain natriuretic peptide (NT-proBNP) and left-ventricular ejection fraction (LVEF). One-year outcomes (n = 11) were assessed using a predefined composite clinical response.

Results: Blood-pool SUV_mean declined from 60 to 120 min, whereas myocardial SUV_mean decreased less, yielding stable TBR(EFM) across time points (60/70/120 min: 2.2 ± 0.8, 2.1 ± 0.9, 2.3 ± 0.9; ANOVA p = 0.596). By contrast, myocardial SUV_mean fell from 3.8 ± 0.7 (60 min) to 2.1 ± 0.9 (120 min; p < 0.001). TBR(EFM) correlated with NT-proBNP at all time-points (60 min r = 0.65, p = 0.007; 120 min r = 0.72, p = 0.003), whereas SUV_mean did not (60 min p = 0.576; 120 min p = 0.109). Baseline TBR(EFM) was significantly lower in one-year responders than non-responders (1.7 ± 0.2 vs. 2.9 ± 0.9; p = 0.013), with separation present at each time point (p < 0.05). Higher baseline TBR(EFM) associated with lower reductions in NT-proBNP at one year (p < 0.05).

Conclusions: Myocardial [⁶⁸Ga]Ga-FAPI TBR may provide a time-robust index of active fibroblast signaling that relates to myocardial hemodynamic stress and stratifies one-year clinical response after TAVI. A single 60-minute acquisition with TBR quantification may be sufficient for myocardial [⁶⁸Ga]Ga-FAPI assessment. These hypothesis-generating findings require validation in larger, multicenter cohorts.

Peptide receptor radionuclide therapy (PRRT) has established itself as a pivotal component in the management of advanced, somatostatin receptor (SSTR)-positive neuroendocrine tumours (NETs). The NETTER-1 phase III trial demonstrated that [¹⁷⁷Lu]Lu-DOTATATE significantly prolongs progression-free survival (PFS) and improves quality of life in patients with midgut NETs refractory to somatostatin analogues, leading to regulatory approval by both EMA (2017) and FDA (2018). The recent NETTER-2 phase III trial further extended these findings by supporting the first-line use of PRRT in Grade 2 and 3 gastroentero-pancreatic (GEP)-NETs (Ki-67 ≥ 10 ≤ 55%). Beyond standard β-emitting therapy, several developments are reshaping the field: the clinical adoption of SSTR antagonists such as radiolabelled JR-11 and LM3, targeted α-particle-emitting therapies (²²⁵Ac, ²¹²Pb, ²¹³Bi) for resistant disease, and rational combination strategies with chemotherapy, DNA-repair inhibitors, and immunotherapy. Parallel innovation in radiopharmaceutical chemistry has yielded new peptide ligands, including cholecystokinin-2 receptor (CCK2R)-targeted compounds such as DOTA-MGS5, which show promise for rare NETs such as medullary thyroid carcinoma (MTC) and small-cell lung cancer (SCLC). This review summarises clinical evidence, translational advances, and future perspectives for PRRT as a cornerstone of precision nuclear oncology. Emphasis is placed on expanding indications, integrating α-emitters, improving safety and dosimetry, and developing novel theragnostic ligands that enable personalised treatment strategies for NETs patients.