Background: Current diagnosis of Transthyretin-related Amyloidosis (ATTR) using bone scintigraphy is primarily based on visual scoring and semi-quantitative indices. With the introduction of new potential life-prolonging drugs for ATTR, a more precise quantification of myocardial amyloid burden is desirable for improved response prediction and therapy monitoring. Methods: At first, quantification experiments using an anthropomorphic thorax phantom were performed. Second, 32 patients underwent both planar whole body [^99mTc]- 3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD)-scintigraphy and quantitative Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) of the thorax. SPECT/CT standardized myocardial uptake values SUVpeak and SUVpeak normalized to bone uptake (nSUVpeak) were determined. Results: Phantom measurements showed a strong linear relationship between the activity in the myocardial insert and the measured activity (r = 0.9998, p = 0.01), but the measured activity was systematically underestimated by approximately 30%. Receiver operating characteristics (ROC) analysis revealed a 100% sensitivity and specificity at a cut-off of 3.1 for SUVpeak for the differentiation of both patient groups. Conclusion: SUV quantification of ATTR amyloid burden is feasible using novel SPECT/CT technology. With a SUVpeak cut-off of 3.1, patients with Perugini grade 2 and 3 could be clearly separated from those with Perugini grade 0 and 1. Besides ATTR diagnostics, quantification of amyloid deposits could potentially be used for therapy monitoring and prognostication in patients with cardiac ATTR.

Background: [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) could affect kidney and salivary gland functions in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: We retrospectively analyzed clinical, renal, and salivary scintigraphy data and salivary [⁶⁸Ga]Ga-PSMA-11 ligand PET scan measures such as metabolic volume and SUVmax values of 27 mCRPC men (mean age 71 ± 7 years) before and 4 weeks after receiving three cycles of PSMA-RLT every 4 weeks. Twenty-two patients additionally obtained renal and salivary scintigraphy prior to each cycle. A one-way ANOVA, post-hoc Scheffé test and Cochran’s Q test were applied to assess organ toxicity. Results: In total, 54 PSMA PET scans, 98 kidney, and 98 salivary scintigraphy results were evaluated. There were no significant differences for the ejection fraction, peak time, and residual activity after 5 min for both parotid and submandibular glands prior to each cycle and 4 weeks after the last cycle. Similarly, no significant differences in serum creatinine and renal scintigraphy parameters were observed prior to each cycle and 4 weeks after the last treatment. Despite there being no changes in the metabolic volume of both submandibular glands, SUVmax values dropped significantly (p < 0.05). Conclusion: Results evidenced no alterations in renal function and only minimal impairment of salivary function of mCRPC patients who acquired an intense PSMA-RLT regimen every 4 weeks.

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [¹⁷⁷Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

Background: Cardiovascular disease (CVD), driven primarily by atherosclerosis, is a major cause of morbidity and mortality among cancer patients. This study aims to evaluate the diagnostic value of [⁶⁸Ga]Ga-FAPI-PET as a novel molecular imaging tool for atherosclerosis, compared with established, non-specific [¹⁸F]FDG. Methods: We retrospectively analyzed twenty patients with bladder cancer who underwent [⁶⁸Ga]Ga-FAPI positron-emission tomography/magnetic resonance (PET/MR) and [¹⁸F]FDG positron emission tomography/computed tomography (PET/CT) at staging. The target-to-background ratio (TBRs) of both tracers were assessed along six arterial segments, and uptake patterns were compared between the two radiotracers. Additionally, associations between the intensity of PET-active lesions and certain CVD risk factors, as well as the intake of acetylsalicylic acid (ASA), were evaluated. Results: [⁶⁸Ga]Ga-FAPI detects significantly more active arterial PET lesions and shows significantly higher uptake than [¹⁸F]FDG in the per-lesion analysis (TBR_FAPI: 1.7 ± 0.5 vs. TBR_FDG: 1.4 ± 0.2; difference 19%; p < 0.001) and in the patient-based analysis (TBR_FAPI: 1.7 ± 0.4 vs. TBR_FDG: 1.4 ± 0.2; difference 19%; p = 0.018). Arterial hypertension (p < 0.001), dyslipidemia (p < 0.001), and particularly type 2 diabetes mellitus (p < 0.001; difference 34%), were significantly associated with elevated [⁶⁸Ga]Ga-FAPI expression compared to [¹⁸F]FDG uptake. ASA therapy was associated with a significant reduction in arterial [⁶⁸Ga]Ga-FAPI expression than [¹⁸F]FDG (p = 0.02). Conclusions: [⁶⁸Ga]Ga-FAPI-PET imaging, demonstrating superior detection of atherosclerotic activity compared to [¹⁸F]FDG, might be a promising molecular imaging marker for atherosclerosis.