[¹⁷⁷Lu]Lu-PSMA^I&T is widely used for the radioligand therapy of metastatic castration-resistant prostate cancer (mCRPC). Since this kind of therapy has gained a large momentum in recent years, an upscaled production process yielding multiple patient doses in one batch has been developed. During upscaling, the established production method as well as the HPLC quality control were challenged. A major finding was a correlation between the specific activity and the formation of a pre-peak, presumably caused by radiolysis. Hence, nonradioactive reference standards were irradiated with an X-ray source and the formed pre-peak was subsequently identified as a deiodination product by UPLC-MS. To confirm the occurrence of the same deiodinated side product in the routine batch, a customized deiodinated precursor was radiolabeled and analyzed with the same HPLC setup, revealing an identical retention time to the pre-peak in the formerly synthesized routine batches. Additionally, further cyclization products of [¹⁷⁷Lu]Lu-PSMA^I&T were identified as major contributors to radiochemical impurities. The comparison of two HPLC methods showed the likelihood of the overestimation of the radiochemical purity during the synthesis of [¹⁷⁷Lu]Lu-PSMA^I&T. Finally, a prospective cost reduction through an optimization of the production process was shown.

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.

The efficacy of radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is currently being investigated for its application in patients with early-stage prostate cancer (PCa). However, little is known about PSMA expression in healthy organs in this cohort. Collectively, 202 [⁶⁸Ga]Ga-PSMA-11 positron emission tomography (PET) scans from 152 patients were studied. Of these, 102 PET scans were from patients with primary PCa and hormone-sensitive biochemically recurrent PCa and 50 PET scans were from patients with metastatic castration-resistant PCa (mCRPC) before and after three cycles of [¹⁷⁷Lu]Lu-PSMA-RLT. PSMA-standardized uptake values (SUV) were measured in multiple organs and PSMA-total tumor volume (PSMA-TTV) was determined in all cohorts. The measured PET parameters of the different cohorts were normalized to the bloodpool and compared using t- or Mann–Whitney U tests. Patients with early-stage PCa had lower PSMA-TTVs (10.39 mL vs. 462.42 mL, p < 0.001) and showed different SUVs in the thyroid, submandibular glands, heart, liver, kidneys, intestine, testes and bone marrow compared to patients with advanced CRPC, with all tests showing p < 0.05. Despite the differences in the PSMA-TTV of patients with mCRPC before and after [¹⁷⁷Lu]Lu-PSMA-RLT (462.42 mL vs. 276.29 mL, p = 0.023), no significant organ differences in PET parameters were detected. These suggest different degrees of PSMA-ligand binding among patients with different stages of PCa that could influence radiotoxicity during earlier stages of disease in different organs when PSMA-RLT is administered.

To investigate the use of kinetic parameters derived from direct Patlak reconstructions of [⁶⁸Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) to predict the histological grade of malignancy of the primary tumor of patients with prostate cancer (PCa). Thirteen patients (mean age 66 ± 10 years) with a primary, therapy-naïve PCa (median PSA 9.3 [range: 6.3–130 µg/L]) prior radical prostatectomy, were recruited in this exploratory prospective study. A dynamic whole-body [⁶⁸Ga]Ga-PSMA-11 PET/CT scan was performed for all patients. Measured quantification parameters included Patlak slope (Ki: absolute rate of tracer consumption) and Patlak intercept (Vb: degree of tracer perfusion in the tumor). Additionally, the mean and maximum standardized uptake values (SUVmean and SUVmax) of the tumor were determined from a static PET 60 min post tracer injection. In every patient, initial PSA (iPSA) values that were also the PSA level at the time of the examination and final histology results with Gleason score (GS) grading were correlated with the quantitative readouts. Collectively, 20 individual malignant prostate lesions were ascertained and histologically graded for GS with ISUP classification. Six lesions were classified as ISUP 5, two as ISUP 4, eight as ISUP 3, and four as ISUP 2. In both static and dynamic PET/CT imaging, the prostate lesions could be visually distinguished from the background. The average values of the SUVmean, slope, and intercept of the background were 2.4 (±0.4), 0.015 1/min (±0.006), and 52% (±12), respectively. These were significantly lower than the corresponding parameters extracted from the prostate lesions (all p < 0.01). No significant differences were found between these values and the various GS and ISUP (all p > 0.05). Spearman correlation coefficient analysis demonstrated a strong correlation between static and dynamic PET/CT parameters (all r ≥ 0.70, p < 0.01). Both GS and ISUP grading revealed only weak correlations with the mean and maximum SUV and tumor-to-background ratio derived from static images and dynamic Patlak slope. The iPSA demonstrated no significant correlation with GS and ISUP grading or with dynamic and static PET parameter values. In this cohort of mainly high-risk PCa, no significant correlation between [⁶⁸Ga]Ga-PSMA-11 perfusion and consumption and the aggressiveness of the primary tumor was observed. This suggests that the association between SUV values and GS may be more distinctive when distinguishing clinically relevant from clinically non-relevant PCa.

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.