Megumi Jinguji

Effects and safety of 131I-metaiodobenzylguanidine (MIBG) radiotherapy in malignant neuroendocrine tumors: Results from a multicenter observational registry

Effective treatments for malignant neuroendocrine tumors are under development. While iodine-131 metaiodobenzylguanidine (¹³¹I-MIBG) radiotherapy has been used in the treatment of malignant neuroendocrine tumors, there are few studies evaluating its therapeutic effects and safety in a multicenter cohort. In the current study, we sought to evaluate the effects and safety of ¹³¹I-MIBG therapy for conditions including malignant pheochromocytoma and paraganglioma within a multicenter cohort. Forty-eight malignant neuroendocrine tumors (37 pheochromocytoma and 11 paraganglioma) from four centers underwent clinical ¹³¹I-MIBG radiotherapy. The tumor responses were observed before and 3 to 6 months after the ¹³¹I-MIBG radiotherapy in accordance with RECIST criteria. We also evaluated the data for any adverse effects. The four centers performed a total of 87 ¹³¹I-MIBG treatments on 48 patients between January 2000 and March 2009. Of the treatments, 65 were evaluable using RECIST criteria. One partial response (PR), 40 stable disease (SD), and 9 progressive disease (PD) in malignant pheochromocytoma were observed after each treatment. Fourteen SD and one PD-were observed in paraganglioma. Patients with normal hypertension (systolic blood pressure (BP) > 130 mmHg) showed significantly reduced systolic BP after the initial follow-up (n=10, 138.1±8.2 to 129.5±13.5 mmHg, P=0.03). In adult neuroendocrine tumors with a treatment-basis analysis, there were side effects following 41 treatments (47.1%) and most of them (90.2%) were minor. In this multicenter registry, PR or SD was achieved in 84.6% of the treatment occasions in adult neuroendocrine tumors through ¹³¹I-MIBG radiotherapy. This indicated that most of the ¹³¹I-MIBG radiotherapy was performed safely without significant side effects.

Three basic patterns of changes in serum thyroid hormone levels in Graves’ disease during the one-year period after radioiodine therapy

The purpose of this study was to clarify the characteristic patterns of the thyroid hormonal changes in Graves’ disease during the one-year period after131I therapy considering that few serial hormonal data during this period are available in the literature.MethodsThe levels of serum T3, T4 and FT4 before and during one year were plotted as a function of time in 70 therapy courses of 58 patients without subsequent antithyroid or steroid therapy.Results35 euthyroid, 6 hypothyroid and 29 hyperthyroid states were obtained during one year after therapy. Although individual patients had individual hormonal changing patterns, 3 common basic patterns were observed from baseline to one month (early) and thereafter (late), respectively. The early patterns were a decrease in 54 (77%), a minimum change in 8 (11.5%) and an increase in 8 (11.5%). The late patterns were a stable state after an initial decrease with a bottom followed by an increase (valley pattern) in 47 (67%), a stable state after an initial increase with a peak followed by a decrease with a bottom and a subsequent re-increase (mountain pattern) in 12 (17%) and a late stable state after a gradual slow decrease without an obvious bottom near or till one year (downhill pattern) in 11 (16%). The bottom level and the degree of hormonal recovery from the bottom determined the stable euthyroid, hypothyroid or hyperthyroid state in 49 (86%) of 57 with the valley or mountain pattern. Most of the bottom levels (81%) and transient abnormal changes including transient hypothyroidism (93%, 13/14), peak or hyperthyroidism (85%, 11/13) and euthyroidism (67%, 10/15) appeared within 6 months. The post-therapeutic stable euthyroid, hypothyroid or hyperthyroid state could be judged from the hormonal patterns in 57% (39/68) from 2.5 to 6 months, in 18% (12/68) from 6 to 9 months and in 25% (17/ 68) thereafter.ConclusionAlthough the changes in thyroid hormones are not constant in Graves’ disease during one year after131I therapy, there are three basic patterns; valley, mountain and downhill patterns from one month after therapy. The post-therapeutic stable state can be judged by the hormonal level recovered from the bottom in most patients.

Diagnosis of Metastases from Postoperative Differentiated Thyroid Cancer: Comparison between FDG and FLT PET/CT Studies

PURPOSE To compare positron emission tomography (PET)/computed tomography (CT) studies performed with the glucose analog fluorine 18 ((18)F) fluorodeoxyglucose (FDG) and the cell proliferation tracer (18)F fluorothymidine (FLT) in the diagnosis of metastases from postoperative differentiated thyroid cancer. MATERIALS AND METHODS The institutional ethics review board approved this prospective study. From March 2010 to February 2012, 20 patients (mean age, 53 years; age range, 22-79 years) with postoperative differentiated thyroid cancer underwent both FDG and FLT PET/CT as a staging work-up before radioiodine therapy. In each patient, 28 anatomic areas were set and analyzed for lymph node and distant metastases. The McNemar exact or χ(2) test was used to examine differences in diagnostic indexes in the detection of lymph node and distant metastases between both tracer PET/CT studies. RESULTS There were 34 lymph node metastases and/or 73 distant metastases (70 metastases in lung and one each in bone, nasopharynx, and brain) in 13 patients. At patient-based analysis, the sensitivity, specificity, and accuracy were 92% (12 of 13 patients), 86% (six of seven patients), and 90% (18 of 20 patients), respectively, for FDG PET/CT and 69% (nine of 13 patients), 29% (two of seven patients), and 55% (11 of 20 patients) for FLT PET/CT. The accuracy of FDG PET/CT was significantly better than that of FLT PET/CT (P = .023). At lesion-based analysis, the sensitivity, specificity, and accuracy for diagnosing lymph node metastases were 85% (29 of 34 lesions), 99.6% (245 of 246 lesions), and 97.9% (274 of 280 lesions), respectively, for FDG PET/CT and 50% (17 of 34 lesions), 90.7% (223 of 246 lesions), and 85.7% (240 of 280 lesions) for FLT PET/CT. The sensitivity, specificity, and accuracy for diagnosing distant metastases were 45% (33 of 73 lesions), 100% (207 of 207 lesions), and 85.7% (240 of 280 lesions), respectively, for FDG PET/CT and 6.8% (five of 73 lesions), 100% (207 of 207 lesions), and 75.7% (212 of 280 lesions) for FLT PET/CT. The sensitivity (P = .002), specificity (P < .001), and accuracy (P < .001) of FDG PET/CT in the diagnosis of lymph node metastases were superior to those of FLT PET, as were the sensitivity (P < .001) and accuracy (P < .001) in the diagnosis of distant metastases. CONCLUSION FDG PET/CT is superior to FLT PET/CT in the diagnosis of postoperative differentiated thyroid cancer lymph node and distant metastases. Thus, FDG PET/CT is more suitable than FLT PET/CT for examining recurrence of postoperative differentiated thyroid cancer.

Scintigraphic progress of the liver in a patient with Alagille syndrome (arteriohepatic dysplasia)

We encountered a 9-year-old Japanese girl with Alagille syndrome. Her scintigraphic examinations of the liver were performed at the ages of 16 months and 9 years.99mTc-PMT, a hepatobiliary imaging agent, was distributed homogeneously in the liver at the younger age, but unevenly produced an area of focally increased uptake in the medial segment of the liver surrounded by peripheral atrophy at the older age.99mTc-GSA, a hepatoreceptor binding agent, was highly accumulated in the area, corresponding to the focally increased uptake of99mTc-PMT. These imaging findings suggest that the pathophysiological and morphological changes of the liver occurred in our patient during the clinical course.

The value of intratumoral heterogeneity of (18)F-FDG uptake to differentiate between primary benign and malignant musculoskeletal tumours on PET/CT.

OBJECTIVE The cumulative standardized uptake value (SUV)-volume histogram (CSH) was reported to be a novel way to characterize heterogeneity in intratumoral tracer uptake. This study investigated the value of fluorine-18 fludeoxyglucose ((18)F-FDG) intratumoral heterogeneity in comparison with SUV to discriminate between primary benign and malignant musculoskeletal (MS) tumours. METHODS The subjects comprised 85 pathologically proven MS tumours. The area under the curve of CSH (AUC-CSH) was used as a heterogeneity index, with lower values corresponding with increased heterogeneity. As 22 tumours were indiscernible on (18)F-FDG positron emission tomography, maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and AUC-CSH were obtained in 63 positive tumours. The Mann-Whitney U test and receiver operating characteristic (ROC) analysis were used for analyses. RESULTS The difference between benign (n = 35) and malignant tumours (n = 28) was significant in AUC-CSH (p = 0.004), but not in SUVmax (p = 0.168) and SUVmean (p = 0.879). The sensitivity, specificity and accuracy for diagnosing malignancy were 61%, 66% and 64% for SUVmax (optical threshold value, >6.9), 54%, 60% and 57% for SUVmean (optical threshold value, >3) and 61%, 86% and 75% for AUC-CSH (optical threshold value, ≤0.42), respectively. The area under the ROC curve was significantly higher in AUC-CSH (0.71) than SUVmax (0.60) (p = 0.018) and SUVmean (0.51) (p = 0.005). CONCLUSION The heterogeneity index, AUC-CSH, has a higher diagnostic accuracy than SUV analysis in differentiating between primary benign and malignant MS tumours, although it is not sufficiently high enough to obviate histological analysis. ADVANCES IN KNOWLEDGE AUC-CSH can assess the heterogeneity of (18)F-FDG uptake in primary benign and malignant MS tumours, with significantly greater heterogeneity associated with malignant MS tumours. AUC-CSH is more diagnostically accurate than SUV analysis in differentiating between benign and malignant MS tumours.

Draft guidelines regarding appropriate use of 131I-MIBG radiotherapy for neuroendocrine tumors

Since the 1980s when clinical therapeutic trials were initiated, 131I-MIBG radiotherapy has been used in foreign countries for unresectable neuroendocrine tumors including malignant pheochromocytomas and neuroblastomas. In Japan, 131I-MIBG radiotherapy has not been approved by the Ministry of Health, Labour and Welfare; however, personally imported 131I-MIBG is now available for therapeutic purposes in a limited number of institutions. These updated draft guidelines aim to provide useful information concerning 131I-MIBG radiotherapy, to help prevent side effects and protect physicians, nurses, other health care professionals, patients and their families from radiation exposure. The committee has also provided appendices on topics such as practical guidance for attending physicians, patient management, and referring physicians.

High FDG and low FLT uptake in a thyroid papillary carcinoma incidentally discovered by FDG PET/CT.

We report a 58-year-old man whose incidentally discovered papillary thyroid carcinoma in the left lobe showed high FDG and low FLT uptake on PET/CT. The SUVmax was 19.7 for FDG and 3.0 for FLT. The Ki-67 labeling index of the tumor was 1.9%. Thus, the low FLT uptake might be attributed to the low proliferative activity of this cancer.

Dexamethasone Suppression FDG PET/CT for Differentiating between True- and False-Positive Pulmonary and Mediastinal Lymph Node Metastases in Non–Small Cell Lung Cancer: A Pilot Study of FDG PET/CT after Oral Administration of Dexamethasone

PURPOSE To examine whether dexamethasone suppression can reduce fluorine 18 fluorodeoxyglucose (FDG) uptake in false-positive (FP) findings in pulmonary and mediastinal lymph nodes in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS Institutional ethics review board approved this prospective study with written informed consent. The study population was composed of 17 patients with NSCLC who underwent both baseline and dexamethasone suppression (24 hours after oral administration of 8 mg dexamethasone) FDG positron emission tomography/computed tomography and surgery. FDG uptake was evaluated by using a five-point visual scoring system (negative findings, score of 0-1; positive findings, score of 2-4) and maximum standardized uptake value (SUVmax). The Mann-Whitney U, Wilcoxon signed-rank, Kruskal-Wallis, or Spearman rank correlation tests were used as necessary for statistical evaluations. RESULTS In 17 primary lesions, no significant difference was noted in visual score between baseline (mean, 3.4 ± 1.2) and dexamethasone suppression scans (mean, 3.3 ± 1.2; P = .16), although SUVmax was significantly lower on dexamethasone suppression scans (mean, 7.1 ± 5.2) than on baseline scans (mean, 8.6 ± 6.6; P = .005). In eight nodes with true-positive (TP) findings, there were no significant differences in visual score (mean for both, 3.8 ± 0.5) and SUVmax (mean, 5.3 ± 2.3 vs 5.5 ± 2.5, respectively; P = .81) between baseline and dexamethasone suppression scans. In 19 nodes with FP findings at baseline, dexamethasone suppression resulted in significantly lowered visual score (mean, 3.4 ± 0.6 vs 2.4 ± 0.8, respectively; P < .001) and SUVmax (mean, 3.5 ± 0.8 vs 2.7 ± 0.7, respectively; P < .001), and four nodes with FP findings were rated as true-negative findings on dexamethasone suppression scans, which resulted in a significant difference in SUVmax between nodal lesions with TP and FP findings (P = .014). CONCLUSION Oral dexamethasone has the potential to reduce FDG uptake in pulmonary and mediastinal nodes with FP findings in NSCLC.

Increased 18F-FDG Uptake in the Spleen and Multiple Lymph Nodes in Dengue Fever.

A 62-year-old man underwent a whole-body FDG PET/CT for annual cancer screening. By an interview, he had an epigastric pain, and his body temperature was 37.0°C on the day. He just came back home from a travel to Southeast Asia 1 week ago and had presented with chill, high fever (temperature, 39.6°C), arthralgia, myalgia, and skin rash a few days before. Dengue fever was diagnosed by detecting dengue virus type 1 genome and antibody to the virus accompanied by thrombocytopenia and leukopenia. PET/CT examination revealed increased FDG uptake in the spleen and multiple lymph nodes.

Vasovagal-related stress immediately before FDG injection may increase bilateral adrenal FDG uptake

OBJECTIVE To evaluate the relationship between vasovagal-related stress on positron emission tomography (PET)/CT and adrenal fludeoxyglucose (FDG) uptake. METHODS We reviewed the medical records of 1358 consecutive patients who underwent FDG PET/CT examinations and selected those who presented with vasovagal-related symptoms and acute hypotension immediately before FDG injection (vasovagal reflex group). Patients who underwent FDG PET/CT examinations on the same days as the vasovagal reflex group without new complaints or any adrenal lesion were used as controls. We evaluated adrenal FDG uptake visually and by means of adrenal maximum standardized uptake value (SUV(max)) and adrenal/liver (A/L) SUV(max) ratio. Next, we reviewed the FDG PET/CT images of the same 1358 patients and selected the cases presenting with bilateral avid FDG uptake. RESULTS 4 patients were included in the vasovagal reflex group, and all of them showed bilateral avid adrenal FDG uptake visually, while 19 patients in the control group did not. The mean adrenal SUV(max) and the mean A/L SUV(max) ratio were significantly higher in the vasovagal reflex group than in the control group (p < 0.001). 10 (0.74%) patients, including 4 patients from the vasovagal reflex group, showed bilateral avid FDG uptake with normal adrenal configuration on CT. CONCLUSION Vasovagal-related stress immediately before FDG injection may increase bilateral adrenal FDG uptake. ADVANCES IN KNOWLEDGE Vasovagal-related stress may be included in the differential diagnosis of the cause of bilateral avid adrenal FDG uptake.