PSMA PET/CT imaging and its application to prostate cancer treatment.

Recognition of the importance of prostate-specific membrane antigen (PSMA) PET/CT in the diagnosis of prostate cancer has steadily increased following the publication of extensive data on its diagnostic accuracy and impact on patient management over the past decade. Several recent clinical trials and investigations regarding PSMA PET/CT have been ongoing in our country, and this examination is expected to become increasingly widespread in the future. This review explains the characteristics of PSMA PET/CT, its diagnostic capabilities and superiority over other modalities, the three proposed PSMA PET/CT interpretation criteria (the European Association of Nuclear Medicine [EANM], the Prostate Cancer Molecular Imaging Standardized Evaluation [PROMISE], and the PSMA Reporting and Data System [PSMA-RADS]), and the application of PSMA PET/CT to prostate cancer treatment (improvement of local control, irradiation of oligometastases, and salvage radiotherapy), incorporating actual clinical images and the latest findings.

Spatial Pattern of Intraprostatic Recurrence after Definitive External-Beam Radiation Therapy for Prostate Cancer: Implications for Focal Boost to Intraprostatic Dominant Lesion.

Purpose: We retrospectively investigated spatial pattern associations between primary and recurrent tumor sites after definitive external-beam radiation therapy (EBRT) for prostate cancer, using positron emission tomography/computed tomography (PET/CT) with a prostate-specific membrane antigen (PSMA)-targeted probe, 18F-FSU-880. Methods and Materials: We used data from our prior phase 2 trial involving patients who received PET/CT with 18F-FSU-880, which was designed to evaluate the tumor detection efficacy of PSMA-PET/CT for recurrent prostate cancer. Data from patients with local intraprostatic recurrence detected by PSMA-PET/CT after definitive EBRT were retrospectively analyzed. The prostate and seminal vesicles were divided into 14 sections. Two diagnostic radiologists separately re-evaluated the intraprostatic location of the primary tumor on magnetic-resonance imaging and that of the recurrent tumor on PSMA-PET/CT, respectively, and the rate of overlap between primary and recurrent tumors was calculated. The overlap rate was defined as "the number of sections that overlapped between the primary tumor and recurrent tumor" divided by "the total number of sections of recurrent tumor". A recurrent tumor was considered to be at the same location as the primary tumor when the overlap rate was equal to or greater than 75%, and a partial overlap was defined as an overlap rate between 25 and 74%. Results: Twelve patients had local recurrence detected by PSMA-PET/CT. The median time to diagnosis of local recurrence was 9.1 (range, 2.2-12.3) years after definitive EBRT. The recurrent tumor was detected at the same location in 25.0%, and a partial overlap was noted in 41.7%. Conclusions: Local intraprostatic recurrence after definitive EBRT often occurs at the same site or at a partially overlapping site adjacent to the primary intraprostatic dominant lesion. Our results support the merit of focal dose-escalation for intraprostatic dominant lesions in definitive EBRT.

Prognostic value of pretreatment FDG PET/CT in uterine cervical cancer according to two major histologic types: squamous cell carcinoma and adenocarcinoma.

Objectives: The aim of this study was to assess the prognostic value of pretreatment Positron emission tomography / computed tomography using 18F-fluorodeoxyglucose (FDG-PET/CT) in cervical cancer according to two major histologic types. Methods: Eighty-three squamous cell carcinoma (SCC) patients and 35 adenocarcinoma (AC) patients who underwent pretreatment FDG-PET/CT were retrospectively analyzed. Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor were calculated. Kaplan-Meier analyses were used to compare correlations between each PET parameter and overall survival (OS). The prognostic values of imaging and clinical parameters were assessed using uni- and multivariable Cox proportional hazard models. Results: SUVmax, SUVmean, and TLG were significantly higher in SCC than in AC (p<0.01 each). No significant difference in MTV was seen between the two groups (p=0.10). As for Kaplan-Meier analyses, in SCC, patients with SUVmax, SUVmean, MTV, and TLG exceeding cutoff values tended to show worse OS than patients with lower values (p=0.07, p=0.27, p<0.01, and p=0.01, respectively, for OS). On the other hand, in AC, patients with MTV and TLG exceeding cutoff values showed significantly worse PFS and OS (p<0.01 each for OS), while SUVmax and SUVmean were unrelated to OS (p=0.91 and p=0.83, respectively for OS). As for multivariable analyses, in SCC, TLG was identified as an independent prognostic factor for OS (p=0.01). In AC, MTV was identified as an independent prognostic factor for OS (p=0.02). Conclusion: Our preliminary data suggest that FDG-PET/CT would be useful for predicting prognosis in cervical cancer, although the clinical significance of quantitative values may differ according to histopathological type.

Assessing Therapeutic Response to Radium-223 with an Automated Bone Scan Index among Metastatic Castration-Resistant Prostate Cancer Patients: Data from Patients in the J-RAP-BSI Trial.

To evaluate the usefulness of change in the automated bone scan index (aBSI) value derived from bone scintigraphy findings as an imaging biomarker for the assessment of treatment response and survival prediction in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223. This study was a retrospective investigation of a Japanese cohort of 205 mCRPC patients who received Ra-223 in 14 hospitals between July 2016 and August 2020 and for whom bone scintigraphy before and after radium-223 treatment was available. Correlations of aBSI change, with changes in the serum markers alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were evaluated. Additionally, the association of those changes with overall survival (OS) was assessed using the Cox proportional-hazards model and Kaplan-Meier curve results. Of the 205 patients enrolled, 165 (80.5%) completed six cycles of Ra-223. Following treatment, ALP decline (%ALP < 0%) was noted in 72.2% (148/205), aBSI decline (%aBSI < 0%) in 52.7% (108/205), and PSA decline (%PSA < 0%) in 27.8% (57/205). Furthermore, a reduction in both aBSI and ALP was seen in 87 (42.4%), a reduction in only ALP was seen in 61 (29.8%), a reduction in only aBSI was seen in 21 (10.2%), and in both aBSI and ALP increasing/stable (≥0%) was seen in 36 (17.6%) patients. Multiparametric analysis showed changes in PSA [hazard ratio (HR) 4.30, 95% confidence interval (CI) 2.32-8.77, p < 0.0001], aBSI (HR 2.22, 95%CI 1.43-3.59, p = 0.0003), and ALP (HR 2.06, 95%CI 1.35-3.14, p = 0.0008) as significant prognostic factors for OS. For mCRPC patients treated with Ra-223, aBSI change is useful as an imaging biomarker for treatment response assessment and survival prediction.

Novel nomogram developed for determining suitability of metastatic castration-resistant prostate cancer patients to receive maximum benefit from radium-223 dichloride treatment-Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial.

PURPOSE: To develop a novel nomogram for determining radium-223 dichloride (Ra-223) treatment suitability for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: This Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial was a retrospective multicenter investigation enrolled 258 mCRPC patients in Japan with Ra-223 treatment between June 2016 and August 2020, with bone scintigraphy findings before treatment, clinical data, and survival outcome available. A nomogram was constructed using prognostic factors for overall survival (OS) based on a least absolute shrinkage and selection operator Cox regression model. A sub-analysis was also conducted for patients meeting European Medicines Agency (EMA) guidelines. RESULTS: Within a median of 17.4 months after initial Ra-223 treatment, 124 patients (48.1%) died from prostate cancer. Predictive factors included (1) sum of prior treatment history (score 0, never prior novel androgen receptor-targeted agents (ARTA) therapy, never prior taxane-based chemotherapy, and ever prior bisphosphonate/denosumab treatment), (2) Eastern Cooperative Oncology Group (ECOG) performance status, (3) prostate-specific antigen doubling time (PSADT), (4) hemoglobin, (5) lactate dehydrogenase (LDH), and (6) alkaline phosphatase (ALP) levels, and (7) automated bone scan index (aBSI) value based on bone scintigraphy. The nomogram using those factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.748 and 0.734, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.771, 0.818, and 0.771, respectively. In 227 patients meeting EMA recommendation, the nomogram with seven factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.722 and 0.704, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.747, 0.790, and 0.759, respectively. CONCLUSION: This novel nomogram including aBSI to select mCRPC patients to receive Ra-223 with significantly prolonged OS possibility was found suitable for assisting therapeutic decision-making, regardless of EMA recommendation.

Detection efficacy of PET/CT with 18F-FSU-880 in patients with suspected recurrent prostate cancer: a prospective single-center study.

PURPOSE: Our objective was to investigate the efficacy of PET/CT with a novel prostate-specific membrane antigen (PSMA)-targeted PET probe, 18F-FSU-880, for detection and localization of recurrent disease in prostate cancer patients in whom recurrence was suspected based on an increase in plasma prostate-specific antigen (PSA) levels after initial treatment. METHODS: This study was a prospective institutional review board-approved study of 72 patients (age 56-84 years, PSA level 0.22-40.00 ng/ml) with suspected relapse of prostate cancer after primary therapy, including radical prostatectomy (RP) (n = 35) or radiation therapy (RT) (n = 37). Patients underwent PET/CT approximately 1 h and 3 h after injection of 18F-FSU-880 (101.8-380 MBq). The correlation between patient-based detection rate and Gleason score (GS) of the primary tumor and plasma PSA levels at the time of PET/CT was evaluated. Maximum standardized uptake values (SUVmax) of the positive uptakes at 1 h post-injection were compared with those at 3 h post-injection. RESULTS: In total, 51 patients (71%) showed at least one positive PSMA PET result. The PSA-stratified detection rates were 22% (2/9), 36% (4/11), 89% (16/18) and 85% (29/34) for PSA levels of 0.2 to < 0.5, 0.5 to < 1.0, 1.0 to < 2.0 and ≥ 2.0 ng/ml, respectively. The GS-stratified detection rates were 33% (2/6), 67% (16/24), 70% (16/23) and 89% (17/19) for GS 6, 7, 8 and 9, respectively. In lesion-based analysis, 157 positive lesions were detected at 3 h post-injection, 18 in the prostate or prostate bed, 65 in lymph nodes, 71 in the bone and 3 in the lung. Two local recurrences, eight pelvic lymph nodes and one distant lymph node were depicted only at 3 h post-injection. SUV max at 3 h post-injection was significantly higher than SUVmax at 1 h post-injection (p < 0.001). CONCLUSION: Our preliminary data suggest that 18F-FSU-880 might be a promising new PSMA-targeting tracer for detecting recurrence after initial treatment in patients with prostate cancer.

Diagnostic Value of DCE-MRI for Differentiating Malignant Adnexal Masses Compared with Contrast-enhanced-T1WI.

PURPOSE: To compare the diagnostic performance of dynamic contrast-enhanced-MR (DCE-MR) and delayed contrast-enhanced (CE)-MRI added to unenhanced MRI, including diffusion weighted image (DWI) for differentiating malignant adnexal tumors, conducting a retrospective blinded image interpretation study. METHODS: Data of 80 patients suspected of having adnexal tumors by ultrasonography between April 2008 and August 2018 were used for the study. All patients had undergone preoperative MRI and surgical resection at our institution. Four radiologists (two specialized in gynecological radiology and two non-specialized) were enrolled for blinded review of the MR images. A 3-point scale was used: 0 = benign, 1 = indeterminate, and 2 = malignant. Three imaging sets were reviewed: Set A, unenhanced MRI including DWI; Set B, Set A and delayed CE-T1WI; and Set C, Set A and DCE-MRI. Imaging criteria for benign and malignant tumors were given in earlier reports. The diagnostic performance of the three imaging sets of the four readers was calculated. Their areas under the curve (AUCs) were compared using the DeLong method. RESULTS: Accuracies of Set B were 81%-88%. Those of Set C were 81%-85%. The AUCs of Set B were 0.83 and 0.89. Those of Set C were 0.81-0.86. For two readers, Set A showed lower accuracy and AUC than Set B/Set C (less than 0.80), although those were equivalent in other readers. No significant difference in AUCs was found among the three sequence sets. Intrareader agreement was moderate to almost perfect in Sets A and B, and substantial to almost perfect in Set C. CONCLUSION: DCE-MR showed no superiority for differentiating malignant adnexal tumors from benign tumors compared to delayed CE-T1WI with conventional MR and DWI.

Physiological FDG uptake in growth plate on pediatric PET.

OBJECTIVES: 18F-Fluorodeoxyglucose (FDG) uptake in children is different from that in adults. Physiological accumulation is known to occur in growth plates, but the pattern of distribution has not been fully investigated. Our aim was to evaluate the metabolic activity of growth plates according to age and location. METHODS: We retrospectively evaluated 89 PET/CT scans in 63 pediatric patients (male : female=25 : 38, range, 0-18 years). Patients were classified into four age groups (Group A: 0-2 years, Group B: 3-9 years, Group C: 10-14 years and Group D: 15-18 years). The maximum standardized uptake value (SUVmax) of the proximal and distal growth plates of the humerus, the forearm bones and the femur were measured. The SUVmax of each site and each age group were compared and statistically analyzed. We also examined the correlations between age and SUVmax. RESULTS: As for the comparison of SUVmax in each location, the SUVmax was significantly higher in the distal femur than those in the other sites (p< 0.01). SUVmax in the distal humerus and the proximal forearm bones were significantly lower than those in the other sites (p< 0.01). In the distal femur, there was large variation in SUVmax, while in the distal humerus and the proximal forearm bones, there was small variation. As for the comparison of SUVmax in each age group, the SUVmax in group D tended to be lower than those in the other groups, but in the distal femur, there was no significant difference among each age group. CONCLUSION: Our data indicate that FDG uptake in growth plates varies depending on the site and age with remarkable uptake especially in the distal femur.

Hyperestrogenism on 18F-FDG PET/CT in a Patient With Estrogen-Producing Ovarian Clear Cell Carcinoma.

A 78-year-old woman was referred to the gynecologic outpatient department because she was suspected of having ovarian cancer based on an imaging study performed during a general medical examination. Further examination using F-FDG PET/CT revealed a bulky mass lesion with low FDG avidity, as well as surprisingly strong bilateral breast radiotracer uptake despite the patient's age. Thus, an estrogen-producing tumor was suspected. Bilateral salpingo-oophorectomy was performed, and surgical pathology diagnosed the tumor as clear cell carcinoma of the ovary.

Evaluation and Optimization of a New PET Reconstruction Algorithm, Bayesian Penalized Likelihood Reconstruction, for Lung Cancer Assessment According to Lesion Size.

OBJECTIVE. The purpose of this study was to characterize the Bayesian penalized likelihood (BPL) reconstruction algorithm in comparison with an ordered subset expectation maximization (OSEM) reconstruction algorithm and to determine its optimal penalization factor (expressed as a beta value) for clinical use. MATERIALS AND METHODS. FDG PET/CT scans of 46 patients with lung cancer were reconstructed using OSEM and BPL with beta values of 200, 300, 400, 500, and 1000. The liver signal-to-noise ratio, mean standardized uptake value (SUVmean) of the liver, and maximum standardized uptake value (SUVmax) and SUVmean of the cancers were measured. Tumors were categorized into three size groups, and the percentage difference in the tumor SUVmax between OSEM and BPL with a beta value of 200 as well as the percentage difference in the SUVmax between BPL with a beta value of 200 and BPL with a beta value of 1000 were calculated. Image quality was assessed by visual scoring. RESULTS. BPL showed a significantly higher liver signal-to-noise ratio than OSEM, except for BPL with a beta value of 200. The liver SUVmean showed no statistical difference among all algorithms. The SUVmax and SUVmean of tumors decreased as the beta value increased. BPL with a beta value of 200 produced a significantly higher tumor SUVmax than did OSEM (p < 0.01), and BPL with a beta value of 400, 500, or 1000 produced a significantly lower tumor SUVmax than did OSEM (p < 0.01). Visual analysis showed the highest and lowest scores for BPL with beta values of 500 and 200, respectively. In the small size group, the percentage difference in the SUVmax between OSEM and BPL with a beta value of 200 and the percentage difference in the SUVmax between BPL with a beta value of 200 and BPL with a beta value of 1000 were significantly larger than that in the other size groups (p < 0.01). CONCLUSION. The BPL algorithm improves image quality without compromising image quantification. A beta value of 500 appeared to be optimal in this study. Smaller tumors were more influenced by BPL.

Placement of a Viabahn stent-graft for hepatic artery pseudoaneurysm complicated by arterial dissection caused by a guiding sheath.

A 69-year-old man was transferred to our hospital for massive hemorrhage from a right hepatic artery pseudoaneurysm 5 months after surgery for gastric cancer. Stent-graft placement was planned to avoid fatal hepatic infarction, and a guiding sheath was advanced deeply into the tortuous and stenotic right hepatic artery beyond the pseudoaneurysm for safe deployment of a stent-graft. However, this advancement caused arterial dissection of the right hepatic artery. After the guiding sheath was pulled back, a Viabahn stent-graft was successfully advanced over a guidewire to exclude the pseudoaneurysm. We consider that a Viabahn stent-graft is more flexible than a guiding sheath and that advancing a Viabahn stent-graft directly from a proximally placed guiding sheath is safer than advancing a guiding sheath into a tortuous and stenotic abdominal artery.

Usefulness of a distal access catheter in embolization of a short gastric artery pseudoaneurysm.

A 59-year-old man was admitted to our hospital for hematemesis. A hematoma was found in the posterior wall of the stomach, but the source of bleeding was not identified. One month later, contrast-enhanced computed tomography revealed a pseudoaneurysm in the short gastric artery. Embolization of the pseudoaneurysm was difficult due to vessel tortuosity. Usage of a distal access catheter improved catheter stability and enabled successful embolization. We consider a distal access catheter to be useful for embolization of an aneurysm beyond a tortuous artery.

Loop formation by an aortic occlusion balloon catheter during resuscitative endovascular balloon occlusion of the aorta (REBOA).

A 77-year-old man was transferred to our hospital for endoscopically uncontrollable active bleeding from a duodenal ulcer. Soon after his arrival, he became hemodynamically unstable and resuscitative endovascular balloon occlusion of the aorta was performed using a 7-F aortic occlusion balloon catheter (Rescue Balloon; Tokai Medical Products, Aichi, Japan). He became hemodynamically stable and was transferred to the CT room. CT demonstrated that the distal part of the catheter shaft had made a loop in the aorta and the balloon was located at the level of the upper abdomen. We consider the low-profile occlusion balloon catheter to be less rigid than large ones, and care should be taken to prevent balloon migration and catheter shaft bending.

Successful embolization of ileal conduit stomal varices with N-butyl cyanoacrylate via a recanalized paraumbilical vein.

A 77-year-old woman with liver cirrhosis was admitted to our hospital for marked hemorrhage in her ileal conduit stoma. She had a history of cystectomy and urinary diversion for bladder carcinoma 2 years ago. Contrast-enhanced CT demonstrated varices in the ileal conduit stoma. We accessed the varices via a recanalized paraumbilical vein to avoid pain from the transhepatic approach, and selectively embolized the varices with N-butyl cyanoacrylate (NBCA). We consider antegrade embolization of ileal conduit stomal varices with NBCA to be effective and feasible. Access via a paraumbilical vein is a useful alternative to the transhepatic approach.

Successful Embolization of Bleeding Ileal Varices with N-butyl Cyanoacrylate via a Recanalized Paraumbilical Vein.

A 48-year-old woman with alcoholic liver cirrhosis was admitted to our hospital because of hematochezia and severe anemia. She had been hospitalized many times over the past year for hematochezia of unknown etiology. Contrast-enhanced CT demonstrated ileal varices, which were fed by several ileal veins. These feeding veins were selectively embolized with N-butyl cyanoacrylate (NBCA) via a recanalized paraumbilical vein. The paraumbilical vein instead of the portal vein was punctured to decrease the risk of bleeding complications because she had coagulopathy and ascites. We consider antegrade embolization of ileal varices with NBCA to be a feasible and effective treatment. Access via a paraumbilical vein is an alternative to the transhepatic approach.Level of Evidence Level V, case report.