Radiation exposure lymphocyte damage assessed by γ-H2AX level using flow cytometry.

DNA double-strand breaks (DSBs) are considered the most relevant lesions to the DNA damage of ionizing radiation (IR), and γ-H2AX foci in peripheral blood lymphocytes are regarded as an adequate marker for DSB quantitative studies. This study aimed to investigate IR-induced DNA damage in mice through γ-H2AX fluorescence analyses by flow cytometry (FCM). The levels of γ-H2AX in CD4/CD8/B220-positive lymphocytes were quantified by FCM through mean fluorescence intensity (MFI) values. Peripheral venous blood samples were collected for evaluation, and all the control groups were restrained from irradiation. For external irradiation experiments, the dose-dependency of MFI values and temporal alternations were assessed both in vitro and in vivo. External radiation exposure damage was positively correlated with the absorbed radiation dose, and the lymphocyte recovered from damage within 3 days. I-131 sodium iodide solution (74 MBq) was injected into the mice intraperitoneally for internal irradiation experiments. Gamma counting and γH2AX foci analyses were performed at 1 h and 24 h by the group. The blood-to-blood S values (Sblood←blood) were applied for the blood-absorbed dose estimation. Internal low-dose-irradiation-induced damage was proved to recover within 24 h. The FCM method was found to be an effective way of quantitatively assessing IR-induced DNA damage.

Recent Advances in Radiopharmaceutical Theranostics of Pheochromocytoma and Paraganglioma.

As a rare kind of non-epithelial neuroendocrine neoplasms, paragangliomas (PGLs) exhibit various clinical characteristics with excessive catecholamine secretion and have been a research focus in recent years. Although several modalities are available nowadays, radiopharmaceuticals play an integral role in the management of PGLs. Theranostics utilises radiopharmaceuticals for diagnostic and therapeutic intentions by aiming at a specific target in tumour and has been considered a possible means in diagnosis, staging, monitoring and treatment planning. Numerous radiopharmaceuticals have been developed over the past decades. 123/131-Metaiodobenzylguanidine (123/131I-MIBG), the theranostics pair target on norepinephrine transporter system, has remained a fantastic protocol for patients with PGLs because of disease control with limited toxicity. The high-specific-activity 131I-MIBG was authorised by the Food and Drug Administration as a systemic treatment method for metastatic PGLs in 2018. Afterward, peptide receptor radionuclide therapy, which uses radiolabelled somatostatin (SST) analogues, has been exploited as a superior substitute. 68Ga-somatostatin analogue (SSA) PET showed significant performance in diagnosing PGLs than MIBG scintigraphy, especially in patients with head and neck PGLs or SDHx mutation. 90Y/177Lu-DOTA-SSA is highly successful and has preserved favourable safety with mounting evidence regarding objective response, disease stabilisation, symptomatic and hormonal management and quality of life preservation. Besides the ordinary beta emitters, alpha-emitters such as 211At-MABG and 225Ac-DOTATATE have been investigated intensively in recent years. However, many studies are still in the pre-clinical stage, and more research is necessary. This review summarises the developments and recent advances in radiopharmaceutical theranostics of PGLs.

Long-term outcomes and prognostic factors of patients with lung metastases from differentiated thyroid cancer after radioiodine therapy in Japan.

Long-term survival in patients with differentiated thyroid cancer (DTC) and lung metastasis remains unexplored in Japan. This study aimed to investigate the long-term survival and prognostic factors of radioiodine therapy (RIT) in a University Hospital setting. This retrospective study included 62 patients with lung metastases from DTC who received RIT between March 2005 and December 2016. According to the 131I whole-body scan and chest computed tomography results, lung metastases were classified as 131I-avid or non-131I-avid, and miliary, micronodular, or macronodular metastases. The 5- and 10-year overall survival (OS) rates from the initial RIT were calculated by the Kaplan-Meier method, and a proportional hazard fit analysis was performed to determine prognostic factors. With a median follow-up of 7.9 years, the 5- and 10-year OS rates from the initial RIT were 93% and 72%, respectively. Univariable and multivariable analyses of patient subgroups revealed that macronodular lung metastases (defined as nodules >1 cm), older age at initial RIT, and high thyroglobulin values (>400 ng/mL) at initial RIT predicted low OS. The 5- and 10-year OS rates of DTC patients with lung metastases were similar to those in previous Japanese reports, which included a smaller sample size compared with ours. Patients with ≤1 cm lung metastases, aged ≤55 years, and a thyroglobulin level of ≤400 ng/mL at the initial RIT had favorable outcomes.

Randomized placebo-controlled double-blind phase II study of zaltoprofen for patients with diffuse-type and unresectable localized tenosynovial giant cell tumors: The REALIZE study.

Background: A tenosynovial giant cell tumor (TGCT) is a locally aggressive benign neoplasm arising from intra- or extra-articular tissue, categorized as localized (L-TGCT, solitary lesion) and diffuse (D-TGCT, multiple lesions) TGCT. Surgical excision is the mainstay of the treatment, and a high local recurrence rate of approximately 50% has been reported. We focused on zaltoprofen, a nonsteroidal anti-inflammatory drug that can activate peroxisome proliferator-activated receptor gamma (PPARγ) and inhibit the proliferation of TGCT stromal cells. Therefore, we conducted a randomized trial to evaluate the safety and effectiveness of zaltoprofen in patients with D-TGCTs or unresectable L-TGCTs. Methods: This randomized, placebo-controlled, double-blind, multicenter trial evaluated the safety and efficacy of zaltoprofen. In the treatment group, zaltoprofen (480 mg/day) was administered for 48 weeks; the placebo group received similar dosages without zaltoprofen. The primary outcome was progression-free rate (PFR) 48 weeks after treatment administration. Disease progression was defined as the following conditions requiring surgical intervention: 1) repetitive joint swelling due to hemorrhage, 2) joint range of motion limitation, 3) invasion of the adjacent cartilage or bone, 4) severe joint space narrowing, and 5) increased tumor size (target lesion). Results: Forty-one patients were allocated to the zaltoprofen (n=21) or placebo (n=20) groups. The PFR was not significant between the zaltoprofen group and the placebo group at 48 weeks (84.0% and 90.0%, respectively; p=0.619). The mean Japanese Orthopedic Association knee score significantly improved from baseline to week 48 in the zaltoprofen group (85.38 versus 93.75, p=0.027). There was a significant difference between the values at 48 weeks of placebo and zaltoprofen group (p=0.014). One severe adverse event (grade 3 hypertension) was observed in the zaltoprofen group. Discussion: This is the first study to evaluate the efficacy and safety of zaltoprofen in patients with TGCT. No significant differences in PFR were observed between the groups at 48 weeks. Physical function significantly improved after zaltoprofen treatment. The safety profile of zaltoprofen was acceptable. This less invasive and safer treatment with zaltoprofen, compared to surgical removal, could be justified as a novel approach to treating TGCT. Further analysis of long-term administration of zaltoprofen should be considered in future studies. Clinical Trial Registration: University Hospital Medical Information Network Clinical Trials Registry, identifier (UMIN000025901).

I-131 metaiodobenzylguanidine therapy is a significant treatment option for pheochromocytoma and paraganglioma.

AIM: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours of chromaffin cells. Several modalities are currently available to treat patients with PPGL. These treatment modalities include surgery, chemotherapy, molecular targeted therapy and radiopharmaceuticals. METHODS: I-131 metaiodobenzylguanidine (mIBG), a classic radiopharmaceutical, can be taken up through specific receptors and sited into many, but not all, PPGL cells. RESULTS: Many studies have investigated the efficacy and toxicity of I-131 mIBG therapy. These studies reported significant results in terms of objective, hormonal and symptomatic responses as well as tolerable toxicities in patients. CONCLUSION: This article reviews the reported experiences of patients who underwent I-131 mIBG therapy for PPGL with a focus on functions and deficiencies of the therapy.

Application of a tungsten apron for occupational radiation exposure in nursing care of children with neuroblastoma during 131I-meta-iodo-benzyl-guanidine therapy.

The use of effective shielding materials against radiation is important among medical staff in nuclear medicine. Hence, the current study investigated the shielding effects of a commercially available tungsten apron using gamma ray measuring instruments. Further, the occupational radiation exposure of nurses during 131I-meta-iodo-benzyl-guanidine (131I-MIBG) therapy for children with high-risk neuroblastoma was evaluated. Attachable tungsten shields in commercial tungsten aprons were set on a surface-ray source with 131I, which emit gamma rays. The mean shielding rate value was 0.1 ± 0.006 for 131I. The shielding effects of tungsten and lead aprons were evaluated using a scintillation detector. The shielding effect rates of lead and tungsten aprons against 131I was 6.3% ± 0.3% and 42.1% ± 0.2% at 50 cm; 6.1% ± 0.5% and 43.3% ± 0.3% at 1 m; and 6.4% ± 0.9% and 42.6% ± 0.6% at 2 m, respectively. Next, we assessed the occupational radiation exposure during 131I-MIBG therapy (administration dose: 666 MBq/kg, median age: 4 years). The total occupational radiation exposure dose per patient care per 131I-MIBG therapy session among nurses was 0.12 ± 0.07 mSv. The average daily radiation exposure dose per patient care among nurses was 0.03 ± 0.03 mSv. Tungsten aprons had efficient shielding effects against gamma rays and would be beneficial to reduce radiation exposures per patient care per 131I-MIBG therapy session.

An open-label, single-arm, multi-center, phase II clinical trial of single-dose [131I]meta-iodobenzylguanidine therapy for patients with refractory pheochromocytoma and paraganglioma.

OBJECTIVE: In this phase II study, we aimed to investigate the efficacy and safety of single-dose [131I]meta-iodobenzylguanidine (131I-mIBG) therapy in patients with refractory pheochromocytoma and paraganglioma (PPGL). PATIENTS AND METHODS: This study was designed as an open-label, single-arm, multi-center, phase II clinical trial. The enrolled patients were administered 7.4 GBq of 131I-mIBG. Its efficacy was evaluated 12 and 24 weeks later, and its safety was monitored continuously until the end of the study. We evaluated the biochemical response rate as the primary endpoint using the one-sided exact binomial test based on the null hypothesis (≤ 5%). RESULTS: Seventeen patients were enrolled in this study, of which 16 were treated. The biochemical response rate (≥ 50% decrease in urinary catecholamines) was 23.5% (90% confidence interval: 8.5-46.1%, p = 0.009). The radiographic response rates, determined with CT/MRI according to the response evaluation criteria in solid tumors (RECIST) version 1.1 and 123I-mIBG scintigraphy were 5.9% (0.3%-25.0%) and 29.4% (12.4%-52.2%), respectively. The most frequent non-hematologic treatment-emergent adverse events (TEAEs) were gastrointestinal symptoms including nausea, appetite loss, and constipation, which were, together, observed in 15 of 16 patients. Hematologic TEAEs up to grade 3 were observed in 14 of 16 patients. No grade 4 or higher TEAEs were observed. All patients had experienced at least one TEAE, but no fatal or irreversible TEAEs were observed. CONCLUSION: A single dose 131I-mIBG therapy was well tolerated by patients with PPGL, and statistically significantly reduced catecholamine levels compared to the threshold response rate, which may lead to an improved prognosis for these patients.

Prognostic factors for refractory pheochromocytoma and paraganglioma after 131I-metaiodobenzylguanidine therapy.

OBJECTIVE: Given the rarity of refractory pheochromocytoma and paraganglioma (PPGL), outcomes and prognostic factors after 131I-metaiodobenzylguanidine (131I-mIBG) treatment still remain unclear. Therefore, this study evaluated whether baseline characteristics at initial 131I-mIBG therapy and imaging response to repeated 131I-mIBG therapy could be prognostic factors for refractory PPGL. METHODS: All patients [n = 59 (male/female = 35/24), median age; 49.3 years] with refractory PPGL who received 131I-mIBG therapy at our institution between September 2009 and September 2019 were retrospectively reviewed for the effects of the following factors on overall survival: age, sex, hypertension, diabetes mellitus, palpitations, constipation, cancer pain, catecholamines values, past history of therapy (external beam radiation for bone metastasis, operation, and chemotherapy), metastasis sites, and response to 131I-mIBG treatments. RESULTS: Throughout the follow-up period, 18 patients died from disease exacerbation. The estimated 5- and 10-year survival rates were 79.4% and 67.2% from the initial diagnoses of refractory PPGL and 68.5% and 49.9% from the first 131I-mIBG therapy, respectively. The multivariate Cox proportional hazards model showed that progressive disease (PD) [hazard ratio (HR) 96.3, P = 0.011] and constipation (HR 8.2, P = 0.024) were adverse prognostic factors for overall survival after initial 131I-mIBG therapy. The log-rank test demonstrated that PD in response to 131I-mIBG therapies (P < 0.0001) and constipation (P < 0.01) were correlated with poor survival rates. CONCLUSIONS: Response to repeated 131I-mIBG treatment can be a strong predictor of prognosis after initial 131I-mIBG therapy for refractory PPGL. Repeated 131I-mIBG therapy may be a good option for controlling refractory PPGL.

[Radiation Protection Against Exposure from Patients Receiving 131I-MIBG and Released from Radiation Treatment Room].

131I-3-iodobenzylguanidine or 131I-iobenguane (3-(131I) iodobenzylguanidine or 131I-iobenguane [131I-MIBG]) is a radioactive agent that is specifically accumulated in tumor cells such as pheochromocytoma and neuroblastoma. Due to its cytotoxic beta ray emitted from 131I, it has been developed as an agent for radioisotope therapy and some researchers have reported its effectiveness. In this study, based on the patients' data from previous clinical trials of 131I-MIBG therapy, we evaluated the radiation safety for public exposure caused by radiation emitted from patients who received 131I-MIBG. In results, it was considered that public exposure and medical exposure of visitors and caregivers to the patients were less than their dose limit and dose constraint by complying the current criteria of the release of patients after therapy with 131I.

Comparison of the detecting capability between 123I-mIBG and post-therapeutic 131I-mIBG scintigraphy for curie scoring in patients with neuroblastoma after chemotherapy.

OBJECTIVE: To evaluate the detecting capability between planar imaging (PI) and PI combined with single-photon emission computed tomography/computed tomography (PICWS), including 123I- and 131I-labeled metaiodobenzylguanidine (mIBG) and to compare the detecting capability between 123I-mIBG and post-therapeutic 131I-mIBG scintigraphy including PI and PICWS for Curie scoring in patients with neuroblastoma. METHODS: Sixty-two patients with 66 pairs of complete images with neuroblastoma were enrolled in this retrospective study. RESULTS: Comparing the Curie scoring between 123I-mIBG PI and PICWS and between post-therapeutic 131I-mIBG PI and PICWS, findings were concordantly negative in 28.79% and 18.18% of studies, concordantly positive in 66.67% and 74.24% of studies, and discordant in 4.54% and 7.58% of studies, respectively. PICWS was superior to PI including 123I- and 131I-mIBG in the evaluation of Curie scoring for neuroblastoma patients (both P < 0.001). Comparing the Curie scores between 123I- and post-therapeutic 131I-mIBG PI and between 123I- and post-therapeutic 131I-mIBG PICWS, concordantly negative imaging was visualized in 22.73% and 19.70% of studies, concordantly positive imaging in 66.67% and 69.70% of studies, and discordant imaging in 10.60% and 10.60% of studies, respectively. Post-therapeutic 131I-mIBG was significantly better than that of 123I-mIBG scintigraphy including PI and PICWS in detecting the Curie scoring for neuroblastoma patients (both P < 0.001). CONCLUSION: The present study demonstrates that 131I- or 123I-mIBG PICWS are more helpful in the evaluation of Curie scores than that of conventional PI and that post-therapeutic 131I-mIBG is superior to 123I-mIBG scintigraphy for the detecting capability of Curie scoring in patients with neuroblastoma.

Diagnostic Use of Post-therapy 131I-Meta-Iodobenzylguanidine Scintigraphy in Consolidation Therapy for Children with High-Risk Neuroblastoma.

123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy is used for evaluating disease extent in children with neuroblastoma. 131I-mIBG therapy has been used for evaluation in children with high-risk neuroblastoma, and post-therapy 131I-mIBG scintigraphy may detect more lesions compared with diagnostic 123I-mIBG scintigraphy. However, no studies have yet revealed the detection rate of hidden mIBG-avid lesions on post-therapy 131I-mIBG whole-body scan (WBS) and SPECT images in neuroblastoma children without mIBG-avid lesions as demonstrated by diagnostic 123I-mIBG scintigraphy. We retrospectively examined the diagnostic utility of post-therapy 131I-mIBG scintigraphy in children who received 131I-mIBG as consolidation therapy. Nineteen children with complete response to primary therapy were examined. Post-therapy 131I-mIBG scintigraphy was performed four days after injection. The post-therapy 131I-mIBG scintigraphy, 4 children exhibited abnormal uptake on the WBS. Post-therapy 131I-mIBG SPECT/CT provided additional information in 2 cases. In total, 6 children exhibited abnormal uptake. The site of abnormal accumulation was on the recurrence site in one case, operation sites in five cases, and bone metastasis in one case. Post-therapy 131I-mIBG scintigraphy could detect residual disease that was not recognized using diagnostic 123I-mIBG scintigraphy in 32% of children with high-risk neuroblastoma and ganglioneuroblastoma. The diagnostic use of post-therapy 131I-mIBG scintigraphy can provide valuable information for detecting residual disease.

High-dose 131I-mIBG as consolidation therapy in pediatric patients with relapsed neuroblastoma and ganglioneuroblastoma: the Japanese experience.

OBJECTIVE: Children with relapsed neuroblastoma have a poor prognosis despite modern multimodality therapy. Novel and more effective therapeutic strategies are required for relapsed neuroblastoma. We retrospectively examined the utility of consolidation therapy with high-dose 131I-meta-iodo-benzyl-guanidine (131I-mIBG) in relapsed neuroblastoma or ganglioneuroblastoma patients with complete response (CR) to induction therapy as demonstrated by diagnostic 123I-mIBG scintigraphy. METHODS: Between December 2009 and 2014, five patients with relapsed neuroblastoma and one with relapsed ganglioneuroblastoma received high-dose 131I-mIBG therapy. Overall and progression-free survival rates at five years after 131I-mIBG therapy were analyzed by the Kaplan-Meier method. RESULTS: During follow-up, three children showed no signs of disease relapse, whereas three died. One child without a relapse died from post-transplant side effects, and two children with a relapse died owing to tumor progression. The 5-year progression-free and overall survival rates after 131I-mIBG therapy were 44% and 67%, respectively. CONCLUSIONS: Consolidation therapy with high-dose 131I-mIBG for patients with 2nd CR showed good overall and progression-free survival. While the risks of radiation exposure must be considered, high-dose 131I-mIBG therapy as consolidation therapy needs to be further investigated.

[The Nationwide Survey on Avoidance of Targeted Radionuclide Therapy in Patients with Limited Activities of Daily Living and Those Undergoing Hemodialysis].

Targeted radionuclide therapy with high-dose radioisotopes should be performed in isolation rooms. Patients can be released only after radioactivity remaining in their bodies becomes less than the limits determined by the release criteria in order to secure public protection. Patients are asked to stay in isolation rooms for a few days. Physicians often face difficulties to carry out therapy in patients with limited activities of daily living and those undergoing hemodialysis, and have to avoid therapy in such cases. The Japanese Society of Nuclear Medicine conducted a nationwide survey in order to find out the actual situation. The survey results should reflect future improvement of therapeutic environment in collaborating with related societies and administrative bodies.

Radiation exposure in nurses during care of 131I-MIBG therapy for pediatric patients with high-risk neuroblastoma.

OBJECTIVE: 131I-meta-iodo-benzyl-guanidine (131I-MIBG) therapy has been used in children with high-risk neuroblastoma, who, in Japan, are cared for by trained nurses. To determine the safety of occupational radiation exposure in nurses, we retrospectively examined radiation exposure during therapy. METHODS: Sixty-two nurses who received radiation exposure during 131I-MIBG therapy were assessed for the daily percentage of total radiation exposure received using the formula, daily radiation exposure/total radiation dose × 100; self-care score of children was evaluated. RESULTS: Fifty-four 131I-MIBG treatments (592 ± 111 MBq/kg) were performed in neuroblastoma patients (M/F; 27 /27, mean age at 131I-MIBG treatment; 7 ± 2 years), who were isolated for 5 ± 1 days. Average total (0.36 ± 0.18 mSv; range 0.09-0.97 mSv) and daily (0.07 ± 0.05 mSv/day; range 0.02-0.32 mSv/day) radiation exposure to nurses per patient care. The daily percentage of total radiation exposure significantly decreased in 3 days after 131I-MIBG treatment (days 0, 1, and 2 was 38.2 ± 14.7%, 26.9 ± 12.6%, and 15.3 ± 7.1%, respectively), and the average self-care score was 12.2 ± 3.5 (10-27) for all patients. Higher self-care score was significantly related to younger patients' age and higher daily radiation exposure in nurses. CONCLUSION: Individual exposure to radiation was well controlled. Nurses who care for pediatric patients needing daily assistance must be aware of the radiation exposure risks, which can be reduced by establishing a care system and monitoring radiation exposure.

High-dose 131I-metaiodobenzylguanidine therapy in patients with high-risk neuroblastoma in Japan.

OBJECTIVE: The aim of the study was to investigate the outcomes and prognostic factors of high-dose 131I-metaiodobenzylguanidine (131I-MIBG) therapy in patients with refractory or relapsed neuroblastoma (NBL) in Japan. METHODS: We retrospectively analyzed 20 patients with refractory or relapsed high-risk NBL who underwent 131I-MIBG therapy with an administration dose ranging from 444 to 666 MBq/kg at Kanazawa University Hospital, Japan, between September 2008 and September 2013. We focused on measurements regarding their initial responses, prognostic factors, survivals, and toxicities following 131I-MIBG therapy using our hospital data and questionnaires from the hospitals that these patients were initially referred from. Furthermore, we performed Kaplan-Meier survival analysis to evaluate event-free survival (EFS) and overall survival (OS). RESULTS: In 19 patients with complete follow-up data, the median age at first 131I-MIBG treatment was 7.9 years (range 2.5-17.7 years). Following 131I-MIBG therapy, 17 of the 19 patients underwent stem-cell transplantations, and their treatment response was either complete (CR) or partial (PR) in three and two cases, respectively. The EFS and OS rates at 1 year following 131I-MIBG therapy were 42% and 58%, respectively, and those at 5 years following 131I-MIBG therapy were 16% and 42%, respectively. Using the two-sample log-rank test, the OS time following 131I-MIBG therapy was significantly longer for < 3-year time interval between the initial diagnosis and 131I-MIBG therapy (p = 0.017), Curie score < 16 just before 131I-MIBG therapy (p = 0.002), without pain (p = 0.002), without both vanillylmandelic acid (VMA) and homovanillic acid (HVA) elevation (p = 0.037) at 131I-MIBG therapy, and with CR or PR following 131I-MIBG therapy (p = 0.015). Although severe hematological toxicities were identified in all 19 patients, severe nonhematological toxicity was not recorded in any patient, except for one patient with grade 3 anorexia and nausea. CONCLUSIONS: High-dose 131I-MIBG therapy in patients with refractory or relapsed high-risk NBL can provide a favorable prognosis without severe nonhematological toxicities. Better prognosis may be anticipated in patients with the initial good response, no pain at 131I-MIBG therapy, no VMA and HVA elevation at 131I-MIBG therapy, low Curie score (< 16) just before 131I-MIBG therapy, and short time interval (< 3 years) between the initial diagnosis and 131I-MIBG therapy.

Utility of 123I-MIBG Standardized Uptake Value in Patients with Refractory Pheochromocytoma and Paraganglioma.

OBJECTIVES: Single-photon emission computed tomography (SPECT) using metaiodobenzylguanidine (MIBG) is an important diagnostic tool for the treatment of refractory pheochromocytoma and paraganglioma (PPGL). Owing to the difficulty of SPECT quantification, the tumour-to-background ratio (TBR) is used to assess disease activity. However, the utility of TBR is limited owing to the background setting. A quantification technique of SPECT/computed tomography (CT) would facilitate image interpretation. This study aimed to assess the relationship between 123I-MIBG maximum standardized uptake value (SUVmax) and TBR and levels of urinary catecholamines and metabolites in patients with refractory PPGL. METHODS: This study included 15 patients with refractory PPGL who underwent 131I-MIBG therapy. Overall, 27 123I-MIBG SPECT/CT images were acquired before and after the therapy. Lesions observed on whole-body images were analysed; the maximum number of lesions per scan was 10. 123I-MIBG SUVmax was semi-automatically calculated using Q. Metrix package (GE Healthcare). TBR was manually calculated according to the following formula: (max count in lesion - max count in background)/max count in background. Background was set in the contralateral area. When a background region of interest could not be set in the area, it was set in the thigh area. Urine was sampled for 24 h to measure catecholamine and metabolite levels. Increases of ≥3-fold were considered abnormal. TBR, 123I-MIBG SUVmax and urinary catecholamine and metabolite levels were compared using linear regression analysis. RESULTS: All patients had MIBG-avid lesions, as seen on 123I-MIBG SPECT/CT. A significant relationship between 123I-MIBG SUVmax and TBR was observed (correlation coefficient [r] =0.84, P < 0.0001). In 27 SPECT/CT examinations, normetanephrine (NMN) level was abnormally increased in 51% (14/27), but other catecholamine and other metabolites were abnormally increased in < 26% (7/27). 123I-MIBG SUVmax strongly correlated with NMN (r=0.76, P < 0.01) and log NMN (r=0.74, P < 0.01). CONCLUSION: 123I-MIBG SUVmax demonstrated similar trends as TBR and reflected urinary NMN in patients with refractory PPGL. Semi-automatic quantification of SPECT/CT could be a useful tool for the evaluation of disease activity.

Nuclear medicine practice in Japan: a report of the eighth nationwide survey in 2017.

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.

Current Consensus on I-131 MIBG Therapy.

Metaiodobenzylguanidine (MIBG) is structurally similar to the neurotransmitter norepinephrine and specifically targets neuroendocrine cells including some neuroendocrine tumors. Iodine-131 (I-131)-labeled MIBG (I-131 MIBG) therapy for neuroendocrine tumors has been performed for more than a quarter-century. The indications of I-131 MIBG therapy include treatment-resistant neuroblastoma (NB), unresectable or metastatic pheochromocytoma (PC) and paraganglioma (PG), unresectable or metastatic carcinoid tumors, and unresectable or metastatic medullary thyroid cancer (MTC). I-131 MIBG therapy is one of the considerable effective treatments in patients with advanced NB, PC, and PG. On the other hand, I-131 MIBG therapy is an alternative method after more effective novel therapies are used such as radiolabeled somatostatin analogs and tyrosine kinase inhibitors in patients with advanced carcinoid tumors and MTC. No-carrier-aided (NCA) I-131 MIBG has more favorable potential compared to the conventional I-131 MIBG. Astatine-211-labeled meta-astatobenzylguanidine (At-211 MABG) has massive potential in patients with neuroendocrine tumors. Further studies about the therapeutic protocols of I-131 MIBG including NCA I-131 MIBG in the clinical setting and At-211 MABG in both the preclinical and clinical settings are needed.

Complete remission of metastatic pheochromocytoma in 123I-metaiodobenzylguanidine scintigraphy after a single session of 131I-metaiodobenzylguanidine therapy: a case report.

BACKGROUND: Pheochromocytomas are rare neuroendocrine tumors, with a malignancy frequency of approximately 10%. The treatment of malignant pheochromocytoma is palliative, and the traditional management strategy has limited efficacy. Furthermore, no clear criteria exist for the treatment of metastatic pheochromocytoma, especially for unresectable lesions. We report a case of complete remission of metastatic pheochromocytoma in 123I-metaiodobenzylguanidine (MIBG) scintigraphy after a single session of 131I-MIBG therapy. CASE PRESENTATION: A 61-year-old woman had a right adrenal grand tumor and lymph node metastasis on the hilum of the right kidney, both of which incorporated MIBG. After surgery, immunostaining of a tumor specimen showed expression of the tumor makers chromogranin and synaptophysin. One year postoperatively, abdominal computed tomography revealed a local recurrence and retroperitoneal lymph node swelling. The local recurrence was positive for MIBG uptake, whereas the swollen retroperitoneal lymph nodes were negative. She underwent surgery again, but the local recurrence was unresectable because of rigid adhesion to the surrounding tissue. Immunostaining of an intraoperatively extracted swollen retroperitoneal lymph node showed expression of tumor markers. The patient then underwent a single session of 131I-MIBG therapy (7.4 GBq, 200 mCi), after which the residual lesions no longer incorporated MIBG, and a complete response in 123I- metaiodobenzylguanidine (MIBG) scintigraphy was achieved. The 131I-MIBG treatment was repeated 6 months later. None of the lesions were positive for MIBG uptake. CONCLUSIONS: 131I-MIBG therapy efficaciously treats unresectable lesions that are positive for MIBG uptake.

Iodine-131 metaiodobenzylguanidine therapy for neuroblastoma: reports so far and future perspective.

Neuroblastoma, which derives from neural crest, is the most common extracranial solid cancer in childhood. The tumors express the norepinephrine (NE) transporters on their cell membrane and take in metaiodobenzylguanidine (MIBG) via a NE transporter. Since iodine-131 (I-131) MIBG therapy was firstly reported, many trails of MIBG therapy in patients with neuroblastoma were performed. Though monotherapy with a low dose of I-131 MIBG could achieve high-probability pain reduction, the objective response was poor. In contrast, more than 12 mCi/kg I-131 MIBG administrations with or without hematopoietic cell transplantation (HCT) obtain relatively good responses in patients with refractory or relapsed neuroblastoma. The combination therapy with I-131 MIBG and other modalities such as nonmyeloablative chemotherapy and myeloablative chemotherapy with HCT improved the therapeutic response in patients with refractory or relapsed neuroblastoma. In addition, I-131 MIBG therapy incorporated in the induction therapy was proved to be feasible in patients with newly diagnosed neuroblastoma. To expand more the use of MIBG therapy for neuroblastoma, further studies will be needed especially in the use at an earlier stage from diagnosis, in the use with other radionuclide formations of MIBG, and in combined use with other therapeutic agents.