Objective 18F-labeled prostate-specific membrane antigen (PSMA) ligand, [18F]PSMA-1007, has the benefit of a higher synthetic yield and minimal excretion in the urine. High detection efficacy was reported in biochemical recurrence (BCR) of prostate cancer after radical prostatectomy. Thus, we evaluated the preliminary diagnostic utility of [18F]PSMA-1007 PET in patients with prostate cancer, focusing on the BCR which is not detected on conventional imaging. Methods We enrolled a total of 28 patients (age 51–79 years) with BCR of prostate cancer. BCR was defined as a continuous increase in PSA after radical prostatectomy or radiation therapy without any apparent recurrent lesions on conventional diagnostic imaging (CT and bone scintigraphy). PSMA-PET scanning was performed approximately 60 min after intravenous injection of [18F]PSMA-1007 (259 ± 37 MBq). PSMA-PET images were evaluated for lesion detection as well as its relation to PSA values and location. Results Abnormal uptake, which was suspected to be recurrence or metastasis, was detected in 92.9% (26/28) of patients with BCR. The SUVmax was 8.4 ± 6.4 in local recurrence, 11.5 ± 11.8 in pelvic lymph nodes (LN), and 4.1 ± 1.6 in bone metastasis. The detection rates were 66.7% in the PSA group-1 (0.1–0.5 ng/mL), 85.7% in the PSA group-2 (0.5–1.0 ng/mL), and 100% in the PSA group-3 (above 1.0 ng/mL). Among the PET-positive BCR patients (n = 26), local recurrence was detected in 57.7% (15/26), pelvic LN in 42.3% (11/26), and bone metastasis in 15.4% (4/26). In 53% (8/15) of BCR patients who were suspected of local recurrence, focal uptake was detected adjacent to the bladder on [18F]PSMA-1007 PET. This suggested the significant advantage of having minimal physiological urine excretion. Conclusions [18F]PSMA-1007 PET showed a high detection rate in recurrent and metastatic lesions. In patients with BCR, its high detection led to suitable treatment strategies, such as salvage radiation therapy or surgical removal of recurrent lymph nodes. Trial registration (UMIN Clinical Trials Registry) UMIN000037697.

Objective In malignant melanoma patients treated with immune checkpoint inhibitor (ICI) therapy, three different FDG-PET criteria, European Organization for Research and Treatment of Cancer (EORTC), PET Response Criteria in Solid Tumors (PERCIST), immunotherapy-modified PERCIST (imPERCIST), were compared regarding response evaluation and prognosis prediction using standardized uptake value (SUV) harmonization of results obtained with various PET/CT scanners installed at different centers. Materials and methods Malignant melanoma patients (n = 27) underwent FDG-PET/CT examinations before and again 3 to 9 months after therapy initiation (nivolumab, n = 21; pembrolizumab, n = 6) with different PET scanners at five hospitals. EORTC, PERCIST, and imPERCIST criteria were used to evaluate therapeutic response, then concordance of the results was assessed using Cohen’s κ coefficient. Log-rank and Cox methods were employed to determine progression-free (PFS) and overall (OS) survival. Results Complete metabolic response (CMR)/partial metabolic response (PMR)/stable metabolic disease (SMD)/progressive metabolic disease (PMD) with harmonized EORTC, PERCIST, and imPERCIST was seen in 3/5/4/15, 4/5/3/15, and 4/5/5/13 patients, respectively. Nearly perfect concordance between each pair of criteria was noted (κ = 0.939–0.972). Twenty patients showed progression and 14 died from malignant melanoma after a median 19.2 months. Responders (CMR/PMR) showed significantly longer PFS and OS than non-responders (SMD/PMD) (harmonized EORTC: p < 0.0001 and p = 0.011; harmonized PERCIST: p < 0.0001 and p = 0.0012; harmonized imPERCIST: p < 0.0001 and p = 0.0012, respectively). Conclusions All harmonized FDG-PET criteria (EORTC, PERCIST, imPERCIST) showed accuracy for response evaluation of ICI therapy and prediction of malignant melanoma patient prognosis. Additional studies to determine their value in larger study populations will be necessary.

PET radioligands with low molar activity (MA) may underestimate the quantity of the target of interest because of competitive binding of the target with unlabeled ligand. The aim of this study was to evaluate the change in the whole-body distribution of 18 F-PSMA-1007 targeting prostate-specific membrane antigen (PSMA) when solutions with different peptide concentrations are used. Methods: Mouse xenograft models of LNCaP (PSMA-positive prostate cancer) (n 5 18) were prepared and divided into 3 groups according to the peptide concentration injected: a high-MA group (1,013 ± 146 GBq/μmol; n 5 6), a medium-MA group (100.7 ± 23.1 GBq/μmol; n 5 6), and a low-MA group (10.80 ± 2.84 GBq/μmol; n 5 6). Static PET scans were performed 1 h after injection (scan duration, 10 min). SUV mean in tumor and normal organs was compared by the multiple-comparison test. Immunohistochemical staining and Western blot analysis were performed to confirm expression of PSMA in tumor, salivary gland, and kidney. Results: The low-MA group (SUV mean , 1.12 ± 0.30) showed significantly lower uptake of 18 F-PSMA-1007 in tumor than did the high-MA group (1.97 ± 0.77) and the medium-MA group (1.81 ± 0.57). On the other hand, in salivary gland, both the low-MA group (SUV mean , 0.24 ± 0.04) and the medium-MA group (0.57 ± 0.08) showed significantly lower uptake than the high MA group (1.27 ± 0.28). The tumor-to-salivary gland SUV mean ratio was 1.73 ± 0.55 in the high-MA group, 3.16 ± 0.86 in the medium-MA group, and 4.78 ± 1.29 in the low-MA group. The immunohistochemical staining and Western blot analysis revealed significant overexpression of PSMA in tumor and low expression in salivary gland and kidney. Conclusion: A decrease in the MA level of the injected 18 F-PSMA-1007 solution resulted in decreased uptake in tumor and, to a greater degree, in normal salivary gland. Thus, there is a possibility of minimizing the adverse effects in salivary gland by setting an appropriate MA level in PSMAtargeting therapy.

Background: [ 18 F]PSMA-1007, a positron emission tomography (PET) tracer, specifically targets prostate-specific membrane antigen (PSMA), which is highly expressed in prostate cancer. PSMA-PET is effective especially for regional detection of biochemical recurrence, which significantly affects patient management. Herein, we established and optimized a one-step radiolabeling protocol to separate and purify [ 18 F]PSMA-1007 with a CFN-MPS200 synthesizer for clinical application. Results: A dedicated single use cassette and synthesis program for [ 18 F]PSMA-1007 was generated using a single-step method for direct precursor radiolabeling. In the cassette, three tube types (fluoro-elastomer, PharMed® BPT, silicone) and two different precursor salts (trifluoroacetic acid or acetic acid) were compared for optimization. Furthermore, three-lot tests were performed under optimized conditions for quality confirmation. Activity yields and mean radiochemical purity of [ 18 F]PSMA-1007 were > 5000 MBq and 95%, respectively, at the end of synthesis, and the decay-corrected mean radiochemical yield from all three cassettes was approximately 40% using a trifluoroacetic acid salt precursor. Fluoro-elastomer tubings significantly increased the amount of non-radioactive PSMA-1007 (8.5 ± 3.1 μg/mL) compared to those with other tubings (0.3 μg/mL). This reduced the molar activity of [ 18 F]PSMA-1007 synthesized in the cassette assembled by fluoroelastomer tubings (46 GBq/μmol) compared to that with PharMed® BPT and silicone tubings (1184 and 1411 GBq/μmol, respectively). Residual tetrabutylammonium, acetonitrile, and dimethyl sulfoxide levels were < 2.6 μg/mL, < 8 ppm, and < 11 ppm, respectively, and ethanol content was 8.0-8.1% in all three cassettes and two different salts. Higher activity yields, radiochemical purities, and decay-corrected radiochemical yields were obtained using an acetic acid salt precursor rather than a trifluoroacetic acid salt precursor (7906 ± 1216 MBq, 97% ± 0%, and 56% ± 4%). In the three-lot tests under conditions optimized with silicone cassettes and acetic acid salt precursor, all quality items passed the specifications required for human use.

PurposeThis study evaluated the effects of new Bayesian penalized likelihood (BPL) reconstruction algorithm on visualization and quantification of upper abdominal malignant tumors in clinical FDG PET/CT examinations, comparing the results to those obtained by an ordered subset expectation maximization (OSEM) reconstruction algorithm. Metabolic tumor volume (MTV) and texture features (TFs), as well as SUV-related metrics, were evaluated to clarify the BPL effects on quantification.Materials and MethodsA total of 153 upper abdominal lesions (82 liver metastatic and 71 pancreatic cancers) were included in this study. FDG PET/CT images were acquired with a GE Discovery 710 scanner equipped with a time-of-flight system. Images were reconstructed using OSEM and BPL (beta 700) algorithms. In 58 lesions &lt;1.5 cm in greatest diameter (small-lesion group), visual image quality of each lesion was evaluated using a four-point scale. SUVmax was obtained for quantitative metrics. Visual scores and SUVmax were compared between OSEM and BPL images. In 95 lesions &gt;2.0 cm in greatest diameter (larger-lesion group), SUVmax, SUVpeak, MTV, and six TFs were compared between OSEM and BPL images. In addition to the size-based analyses, an increase of SUVmax with BPL was evaluated according to the original SUVmax in OSEM images.ResultsIn the small-lesion group, both visual score and SUVmax were significantly higher in the BPL than OSEM images. The increase in visual score was observed in 20 (34%) of all 58 lesions. In the larger-lesion group, no statistical difference was observed in SUVmax, SUVpeak, or MTV between OSEM and BPL images. BPL increased high gray-level zone emphasis and decreased low gray-level zone emphasis among six TFs compared to OSEM with statistical significance. No statistical differences were observed in other TFs. SUVmax-based analysis demonstrated that BPL increased and decreased SUVmax in lesions with low (&lt;5) and high (&gt;10) SUVmax in original OSEM images, respectively.ConclusionThis study demonstrated that BPL improved conspicuity of small or low-count upper abdominal malignant lesions in clinical FDG PET/CT examinations. Only two TFs represented significant differences between OSEM and BPL images of all quantitative metrics in larger lesions.