Evaluation of PSMA expression changes on PET/CT before and after initiation of novel antiandrogen drugs (enzalutamide or abiraterone) in metastatic castration-resistant prostate cancer patients Abstract Objective To investigate the association between Prostate-Specific Membrane Antigen (PSMA) expression changes on positron emission tomography–computed tomography (PET/CT) and the response to treatment following the start of enzalutamide or abiraterone in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods All consecutive 68Ga-PSMA-11 PET/CT scans routinely performed at our institution during more than 4 years were retrospectively screened for inclusion. We included mCRPC patients with a baseline PSMA PET/CT performed less than 2 months before the start of either enzalutamide or abiraterone, and a follow-up PSMA PET/CT performed no more than a year after, while still under those novel antiandrogen drugs (NAD). The associated clinical records were reviewed. Patients were considered treatment responders if they presented decreasing PSA levels > 50% or a radiological response based on RECIST 1.1 criteria. PSMA expression changes on the follow-up PET/CT were assessed using per-patient dominant response criteria to classify patients as PSMA-responders (complete disappearance of pathologic PSMA uptake, or a decreased uptake of the majority of lesions) or PSMA-non-responders (new PSMA-expressing lesions, increased uptake of the majority of lesions, or stable PSMA expression of the disease). Descriptive statistics and measures of associations (two-sided Fisher’s exact test and Phi coefficient) were calculated. Results A total of 11 and 15 patients were included in the enzalutamide and abiraterone groups. Median follow-up was 110 (IQR 76–124) and 87 (IQR 71–242) days, respectively. All treatment responders (3 enzalutamide and 4 abiraterone) were considered PSMA-responders, and all treatment non-responders (8 enzalutamide, 11 abiraterone) were considered PSMA-non-responders. PSMA PET response was thus perfectly associated with conventional response criteria (p = 0.006, Phi = 1 for enzalutamide; p = 0.001, Phi = 1 for abiraterone). In our cohort, no PSMA expression flare phenomenon was detected on follow-up PET/CT scans at a median follow-up of 3 months. However, an early and short-lived flare cannot be excluded. Conclusions This retrospective study suggests that, after a median follow-up of 3 months under enzalutamide or abiraterone, PSMA expression changes on PET/CT are strongly associated with response to treatment. Prospective studies are needed to better understand PSMA expression dynamics following the start of enzalutamide and abiraterone, along with the role of PSMA PET/CT in response assessment.

Response to Dr. Kameyama’s letter to the editor

No delayed imaging or CCK administration is needed in most cases when bowel excretion does not occur but gallbladder fills promptly Abstract Objective On hepatobiliary scintigraphy, “preferential gallbladder (GB) filling without tracer excretion into the small bowel (SB) [p-GB-no-SB]” is occasionally seen on images obtained up to an hour. In such cases, many practitioners administer cholecystokinin (CCK) (even when the measurement of GB ejection fraction is not indicated) or obtain delayed images (DI) to exclude common bile duct (CBD) obstruction. We aimed (1) to assess the prevalence of clinically relevant CBD obstruction found by CCK administration or DI in this circumstance and (2) to find imaging findings and/or parameters that can be used to triage patients who do or do not need such maneuvers. Methods Of 1244 scans reviewed, 1089 were excluded because of one or more of the following reasons: SB visualized within 60 min, GB not visualized within 60 min, severely decreased hepatic function, and less than 1 month of clinical follow-up after scanning. The remaining 155 showed p-GB-no-SB with clinical follow-up available for ≥ 1 month. For the 155 scans, clearance of liver parenchymal activity was assessed. Results Of the 155 scans, 142 showed visually prompt clearance of liver parenchymal activity (group A), while 13 scans showed mild to moderately delayed clearance of liver parenchymal activity with or without initial decreased hepatic uptake (group B). 134 of 142 in group A had additional imaging (99 CCK or 35 DI); all 134 showed SB visualization. Eight remaining scans were terminated without additional imaging. None of the 142 had any event attributable to CBD obstruction on follow-up. All 13 in group B had additional imaging (9 CCK, 4 DI); SB visualized in 11, but not in two; clinical follow-up revealed no CBD obstruction in 11. ERCP revealed CBD obstruction in the latter two. Conclusions When a HIDA scan shows p-GB-no-SB, the probability of identifying clinically relevant CBD obstruction by additional imaging with CCK or DI is virtually zero in an acute clinical setting if clearance of liver parenchymal activity is prompt. Additional imaging with CCK or DI can be reserved for only those showing abnormal clearance of liver parenchymal activity.

Model for age-dependent decline in dopamine transporter

Fully automated analysis for bone scintigraphy with artificial neural network: usefulness of bone scan index (BSI) in breast cancer Abstract Objective Artificial neural network (ANN) technology has been developed for clinical use to analyze bone scintigraphy with metastatic bone tumors. It has been reported to improve diagnostic accuracy and reproducibility especially in cases of prostate cancer. The aim of this study was to evaluate the diagnostic usefulness of quantitative bone scintigraphy with ANN in patients having breast cancer. Patients and methods We retrospectively evaluated 88 patients having breast cancer who underwent both bone scintigraphy and 18F-fluorodeoxyglucose (FDG) positron-emission computed tomography/X-ray computed tomography (PET/CT) within an interval of 8 weeks between both examinations for comparison. The whole-body bone images were analyzed with fully automated software that was customized according to a Japanese multicenter database. The region of interest for FDG-PET was set to bone lesions in patients with bone metastasis, while the bone marrow of the ilium and the vertebra was used in patients without bone metastasis. Results Thirty of 88 patients had bone metastasis. Extent of disease, bone scan index (BSI) which indicate severity of bone metastasis, the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and serum tumor markers in patients with bone metastasis were significantly higher than those in patients without metastasis. The Kaplan–Meier survival curve showed that the overall survival of the lower BSI group was longer than that with the higher BSI group in patients with visceral metastasis. In the multivariate Cox proportional hazard model, BSI (hazard ratio (HR): 19.15, p = 0.0077) and SUVmax (HR: 10.12, p = 0.0068) were prognostic factors in patients without visceral metastasis, while the BSI was only a prognostic factor in patients with visceral metastasis (HR: 7.88, p = 0.0084), when dividing the sample into two groups with each mean value in patients with bone metastasis. Conclusion BSI, an easily and automatically calculated parameter, was a well prognostic factor in patients with visceral metastasis as well as without visceral metastasis from breast cancer.

68Ga-PSMA-11 PET/CT derived quantitative volumetric tumor parameters for classification and evaluation of therapeutic response of bone metastases in prostate cancer patients Abstract Background To evaluate the role of 68Gallium prostate-specific membrane antigen-positron emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) derived quantitative volumetric tumor parameters in comparison with fully diagnostic conventional CT and serum-PSA levels for classification and evaluation of therapeutic response of bone metastases in patients with metastasized prostate cancer (PC). Methods A total of 177 men with biochemical recurrence of prostate cancer suffering from bone metastases underwent PET/CT with [68Ga] Ga-PSMA-HBED-CC (68Ga-PSMA-11). To calculate 68Ga-PSMA-11 PET quantitative volumetric tumor parameters including whole-body total-lesion PSMA (TL-PSMA), whole-body PSMA-tumor volume (PSMA-TV), as well as the established maximum standard uptake values (SUVmax) and mean standard uptake values (SUVmean), all 443 68Ga-PSMA-11-positive bone lesions in the field of view were assessed quantitatively. Quantitative volumetric tumor parameters were correlated with CT-derived volume and bone density measurements of metastatic bone lesions, serum prostate-specific antigen (PSA) levels, and Gleason Scores. In the 20 patients suffering from bone metastases who underwent 68Ga-PSMA-11 PET/CT before and after therapy, CT-derived volume and bone density measurements of metastatic lesions were compared to biochemical response determined by serum-PSA levels. Results In 177 patients, a total of 443 68Ga-PSMA-11 PET-positive bone lesions were detected. Of these, 50 lesions (11%) were only detectable on PET but not on conventional CT. PET-positive/CT-negative bone metastases demonstrated a significantly lower PSMA uptake compared to PET-positive/CT-positive bone lesions (p < 0.05). SUVmax, SUVmean, PSMA-TV, and TL-PSMA of bone metastases were significantly higher (p < 0.05) in patients with Gleason Scores > 7 compared to those with Gleason Scores ≤ 7. In the linear regression analysis, an association was determined between SUVmean, Gleason Scores, lesion classification, and serum-PSA levels but not for CT-derived bone density measurements. No significant correlation could be found between changes of bone density and CT-derived volume measurements of metastatic bone lesions and changes of serum-PSA levels (p > 0.05) before and after therapy, while a highly significant correlation was observed for changes of PSMA-TV, TL-PSMA, and serum-PSA levels (p < 0.001). Conclusion Our results suggest that 68Ga-PSMA-11 PET/CT might be a valuable tool for the detection and follow-up of bone metastases in patients with metastasized prostate cancer. 68Ga-PSMA-11 PET-derived quantitative volumetric parameters demonstrated a highly significant correlation with changes of serum-PSA levels during the course of therapy. No such correlation could be determined for bone density measurements of metastatic bone lesions. Compared to the fully diagnostic CT scan, a significantly higher proportion of bone metastases was detected on 68Ga-PSMA-11 PET.

Nuclear medicine practice in Japan: a report of the eighth nationwide survey in 2017 Abstract Objective Subcommittee on Survey of Nuclear Medicine Practice in Japan has performed a nationwide survey of nuclear medicine practice every 5 years since 1982 to survey contemporary nuclear medicine practice and its changes over the years. Methods The subcommittee sent questionnaires, including the number and category of examinations as well as the kind and dose of the radiopharmaceuticals during the 30 days of June 2017, to all nuclear medicine institutes. The total numbers for the year 2017 were then estimated. Results A total of 1132 institutes responded to the survey, including 351 PET centers. The recovery rate was 90.6%. The number of gamma cameras installed was 1332 in total, with 7.0% decrease in 5 years. Dual-head cameras and hybrid SPECT/CT scanners accounted for 88.2 and 23.6%, respectively. The number of single-photon tracer studies in 2017 was 1.08 million which means a decrease in 5.7% in 5 years and 23.6% in 10 years. All but neurotransmitter system, sentinel lymph node, and liver scintigraphy decreased. Bone scintigraphy was a leading examination (32.3%), followed by myocardial scintigraphy (24.1%) and cerebral perfusion study (18.0%) in order. SPECT studies showed an increase from 47.2% to 63.5%. PET centers have also increased from 295 to 389, as compared to the last survey. The 112 PET centers have installed one or two in-house cyclotrons. PET studies showed 24.5% increase in 5 years, with oncology accounting for 88.9%. 18F-FDG accounted for 98.2% (630,570 examinations). PET examinations using 11C-methionine have decreased, with 2440 examinations in 2017. PET examinations using 13N-NH3 have been increasing, with 2363 examinations in 2017. The number of PET studies using 11C-PIB was 904. 131I-radioiodine targeted therapies showed an increase in 5 years (23.1%), including 4487 patients for thyroid cancer. Out-patient thyroid bed ablation therapy with 1,110 MBq of 131I accounted for 36.6% of cancer patients. The number of admission rooms increased from 135 to 157 in 5 years. The number of 223Ra targeted therapies for castration-resistant metastatic prostate cancer was 1194 patients. Conclusions Single-photon examinations showed a continuous tendency toward a decline in the survey. In contrast, the number of hybrid SPECT/CT scanner examinations has increased. PET/CT study and radionuclide targeted therapy have steadily increased.

Clinical utility of SPECT/CT and CT-dacryocystography-enhanced dacryoscintigraphy in the imaging of lacrimal drainage system obstruction Abstract Purpose Epiphora is commonly caused by a relative or complete occlusion in the lacrimal drainage system (LDS), principally a nasolacrimal duct obstruction (NLDO). Dacryoscintigraphy (DSG), an extensively assessed imaging technique in diagnosing its abnormalities, can provide only planar images, according to which it needs to be improved. Our aim was to evaluate clinical utility of simultaneous DSG and single-photon emission computed tomography/computed tomography (SPECT/CT) combined with computed tomographic dacryocystography (CT-DCG) in the evaluation of LDS. Methods Dynamic imaging with DSG was performed, and tracer radioactivity was detected by a gamma camera. Successively, SPECT/CT images of the involved region were gained, followed by CT-DCG, during which a contrast medium was syringed into the affected LDS, and finally contrast CT scans were obtained again from the same region. Results Fifty-seven patients, mean age 54.25 (± 18.26) years all with unilateral NLDO and 32 control subjects, all with patent LDS, mean age 49.88 (± 18.61) years were evaluated in the study. Delayed outflow of tearing eyes was exposed to DSG compared to the fellow and control eyes. The highest value for sensitivity was observed for SPECT/CT, followed by CT-DCG and DSG techniques, while combining DSG with SPECT/CT, DSG with CT-DCG, and SPECT/CT with CT-DCG, the sensitivity increased to 96.49%, 92.98%, and 94.73%, respectively. Conclusions Although DSG is a sensitive nuclear medicine method, it only provides useful clinical data when simultaneously supplemented with SPECT/CT and CT-DCG trials as they jointly can offer valuable information about the localization of an abnormality and verify stenosis or obstruction.

Al 18 F-labeled alpha-melanocyte-stimulating hormone (α-MSH) peptide derivative for the early detection of melanoma Abstract Objective Early detection plays a role in the prognosis of melanoma, the most aggressive skin cancer. 64Cu- and 68Ga-labeled alpha-melanocyte-stimulating hormone (α-MSH) analogs targeting the melanocortin-1 receptor are promising positron emission tomography (PET) tracers for detecting melanoma, and the use of 18F-labeling will further contribute to the detectability and availability. However, the high radiochemistry demand related to the conventional 18F-labeling methods has restricted the development of 18F-labeled α-MSH analogs. A recently developed radiofluorination method using aluminum-fluoride (Al18F) offers a simple, efficient, and time-saving labeling procedure compared to the conventional 18F-labeling methods. Herein, we sought to establish a simple preparation method for an 18F-labeled α-MSH analog using Al18F, and we examined its potential for the early detection of melanoma. Methods A 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA)-conjugated α-MSH analog (NOTA-GGNle-CycMSHhex) was prepared by the Fmoc solid-phase strategy. NOTA-GGNle-CycMSHhex was labeled with Al18F by heating at 105 °C using a microwave synthesizer for 15 min. Biodistribution study was conducted on B16/F10-luc melanoma-bearing mice at 30 min, 1 h and 3 h after injection of Al18F-NOTA-GGNle-CycMSHhex. PET imaging was conducted on melanoma-bearing mice at 1 h post-injection. One day prior to the PET imaging, bioluminescence imaging was also performed. Results Al18F-NOTA-GGNle-CycMSHhex was readily prepared with a high radiochemical yield (94.0 ± 2.8%). The biodistribution study showed a high accumulation of Al18F-NOTA-GGNle-CycMSHhex in the tumor at 30 min and 1 h post-injection (6.69 ± 1.49 and 7.70 ± 1.71%ID/g, respectively). The tumor-to-blood ratio increased with time: 3.46 ± 0.89, 12.67 ± 1.29, and 35.27 ± 9.12 at 30 min, 1 h, and 3 h post-injection, respectively. In the PET imaging, Al18F-NOTA-GGNle-CycMSHhex clearly visualized the tumors and depicted very small tumors (< 3 mm). Conclusions We successfully prepared Al18F-NOTA-GGNle-CycMSHhex in a simple and efficient manner. Al18F-NOTA-GGNle-CycMSHhex showed high tumor accumulation and clearly visualized very small tumors in melanoma-bearing mice. These findings suggest that Al18F-NOTA-GGNle-CycMSHhex will be a promising PET tracer for melanoma imaging at an earlier stage.

Quantitative SPECT/CT imaging for medication-related osteonecrosis of the jaw: a preliminary study using volume-based parameters, comparison with chronic osteomyelitis Abstract Objective To investigate the quantitative SPECT/CT imaging for medication-related osteonecrosis of the jaw (MRONJ) using volume-based parameters. Methods Thirteen patients with mandibular lesions (nine MRONJ and four chronic osteomyelitis) underwent SPECT/CT acquisition at 4 h after injection of technetium 99m hydroxymethylene diphosphonate. Then, reconstruction of the acquired data and underwent voxel-based quantitative analysis using GI-BONE software. The parameters of the quantitative manner, such as maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), mean SUV (SUVmean), metabolic bone volume (MBV) and total bone uptake (TBU), were compared for the mandibular lesions. Statistical analyses for the quantitative parameters of mandibular lesions were performed by Mann–Whitney U test. A p value lower than 0.05 was considered as statistically significant. Results Then, reconstruction of these quantitative parameters, SUVmax (10.16 ± 0.96), SUVpeak (7.95 ± 0.88), SUVmean (5.90 ± 0.86) and TBU (94.22 ± 57.44) for chronic osteomyelitis were significantly higher than those for MRONJ [5.50 ± 2.47 (p = 0.020), 4.10 ± 1.85 (p = 0.011), 2.74 ± 1.07 (p = 0.006) and 29.88 ± 15.46 (p = 0.034), respectively]. Conclusions SUVmax, SUVpeak, SUVmean and TBU derived from bone SPECT/CT and voxel-based quantitative parameters may be useful for the evaluation of mandibular lesions, such as MRONJ and chronic osteomyelitis.