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Objective: This study sought to assess the safety, efficacy, impact on hypothyroid symptoms, and pharmacokinetics of SKG-02 (rhTSH, thyrotropin alfa) in the diagnostic follow-up of Japanese patients with well-differentiated thyroid carcinoma (WDTC)., Methods: Ten Japanese adults with WDTC were enrolled into a prospective, multicenter, open-label trial comparing diagnostic whole-body scintigraphy (dxWBS) and serum thyroglobulin (Tg) testing aided by SKG-02 versus these procedures aided by thyroid hormone withdrawal (THW). Patients were their own controls. Variables compared included scan set ability to detect radioiodine uptake by remnant or malignant thyroid tissue, scan set quality, diagnostic sensitivity of dxWBS and Tg testing alone or combined, frequency of hypothyroid signs/symptoms, and adverse events (AEs). SKG-02 pharmacokinetic variables including maximum concentration (Cmax), time to Cmax (Tmax) and the area under the time-concentration curve (AUC) were calculated., Results: In a blinded evaluation by an independent committee of 3 nuclear medicine experts, 70% of SKG-02 dxWBS scan sets were rated "equivalent" (n = 7) or "superior" (n = 0) to their THW counterparts in ability to detect radioiodine uptake in healthy or malignant thyroid tissue. Therefore the study exceeded its primary endpoint of a 60% equivalence/superiority rate. SKG-02 Tg testing identified 3/3 cases of disease. Hypothyroid signs/symptoms were substantially more frequent during THW than during euthyroidism permitted by SKG-02 use. SKG-02 was well-tolerated, with no severe or serious drug-related AEs. Cmax was 240.8 +/- 65.9 microIU/ml, Tmax was 28.75 +/- 14.21 hr after the first SKG-02 injection, and AUC was 11,414 +/- 3,462 microIU hr/ml in 9 patients evaluable for pharmacokinetics., Conclusions: SKG-02 was safe and effective in the diagnostic follow-up of Japanese patients with WDTC, avoiding hypothyroid morbidity relative to THW. These and the pharmacokinetic findings were similar to those of overseas Phase III studies.

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2006 in Japan. It was based on responses to questionnaires sent to nuclear medicine institutions. The reply was obtained from 975 institutions among 1263 to which the questionnaire had been sent. Thirty-two cases of adverse reactions were reported. A total of 1,189,127 radiopharmaceutical administrations was reported. The incidence of adverse reactions per 100,000 cases was 2.7. Three cases of defect products were reported, and the incidence of defect products per 100,000 cases was 0.3.

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2005 in Japan. It was based on responses to questionnaires sent to nuclear medicine institutions. The reply was obtained from 1,007 institutions among 1,243 to which the questionnaire had been sent. Nineteen cases of adverse reactions were reported. A total of 1,264,098 radiopharmaceutical administrations was reported. The incidence of adverse reactions per 100,000 cases was 1.5. Three cases of defect products were reported, and the incidence of defect products per 100,000 cases was 0.2.

This survey was performed in order to investigate the incidence of adverse reactions to radiopharmaceuticals and defect products in FY2004 in Japan. It was based on responses to questionnaires sent to nuclear medicine institutions. The reply was obtained from 968 institutions among 1,220 to which the questionnaire had been sent. Sixteen cases of adverse reactions were reported. A total of 1,277,906 radiopharmaceutical administrations was reported. The incidence of adverse reactions per 100,000 cases was 1.3. Eight cases of defect products were reported, and the incidence of defect products per 100,000 cases was 0.6.

Radio-iodine (131I) therapy has been using in Graves' disease and well differentiated thyroid cancer. The rules of control in the discharge from radio-isotope hospital were notified in 1999 in Japan. Guideline of the 131I therapy in Graves' disease and thyroid cancer were prepared by sub-group of Japanese Society of Nuclear Medicine.

To explore the possibility of which medical radioactive wastes could be disposed as general wastes after keeping them a certain period of time and confirming that their radioactivity reach a background level (BGL), we made a survey of these wastes in several nuclear medicine facilities. The radioactive wastes were collected for one week, packed in a box according to its half-life, and measured its radioactivity by scintillation survey meter with time. Some wastes could reach a BGL within 10 times of half-life, but 19% of the short half-life group (group 1) including 99mTc and 123I, and 8% of the middle half-life group (group 2) including 67Ga, (111)In, and 201Tl did not reach a BGL within 20 times of half-life. A reason for delaying the time of reaching a BGL might be partially attributed to high initial radiation dose rate or heavy package weight. However, mixing with the nuclides of longer half-life was estimated to be the biggest factor affecting this result. When disposing medical radioactive wastes as general wastes, it is necessary to avoid mixing with radionuclide of longer half-life and confirm that it reaches a BGL by actual measurement.

We conducted a questionnaire survey about radiation-safety management condition in Japanese nuclear medicine facilities to make materials of proposition for more reasonable management of medical radioactive waste. We distributed a questionnaire to institutions equipped with Nuclear Medicine facilities. Of 1,125 institutions, 642 institutes (52.8%) returned effective answers. The questionnaire covered the following areas: 1) scale of an institution, 2) presence of enforcement of radiotherapy, 3) system of a tank, 4) size and number of each tank, 5) a form of draining-water system, 6) a displacement in a radioactive rays management area, 7) a measurement method of the concentration of medical radioactive waste in draining water system, 8) planned and used quantity of radioisotopes for medical examination and treatment, 9) an average displacement of hospital for one month. In most institutions, a ratio of dose limitation of radioisotope in draining-water system was less than 1.0, defined as an upper limitation in ordinance. In 499 hospitals without facilities of hospitalization for unsealed radioisotope therapy, 473 hospitals reported that sum of ratios of dose limits in a draining-water system was less than 1.0. It was calculated by used dose of radioisotope and monthly displacement from hospital, on the premise that all used radioisotope entered in the general draining-water system. When a drainage including radioactivity from a controlled area join with that from other area before it flows out of a institution, it may be diluted and its radioactive concentration should be less than its upper limitation defined in the rule. Especially, in all institutions with a monthly displacement of more than 25,000 m3, the sum of ratio of the concentration of each radionuclide to the concentration limit dose calculated by used dose of radioisotope, indicated less than 1.0.

A survey on the I-131 therapy of Graves' hyperthyroidism was undertaken by questionnaire in 1,246 hospitals of Japan. One thousand and ninety seven of them (88.0%) responded to the questionnaire. In this paper, we report the results and analysis of the replies to the questionnaire. In the 121 hospitals (11.03%) of the respondents, I-131 therapy is being performed for Graves' hyperthyroidism. A gradual increase was observed in the annual number of I-131 treated Graves' disease patients during the period of 1998-2001, from 1,740 to 2,484. I-131 treatment was selected mainly for the cases with side effects from antithyroid drug (ATD) therapy, followed by the cases with complication of heart or hepatic diseases, recurrences of hyperthyroidism after surgery, radioiodine treatment, and long-term ATD treatment. The 41% of respondents used I-131 in order to restore euthyroidism, 34% aimed for hyperthyroidism and 41% used the dose properly between the two according to the patients. Administration dosage of I-131 was estimated mainly on the basis of thyroid uptake and volume in 93% of the respondents and 48% calculated the radiation dose by also determining the effective half-life in the thyroid gland. Thyroid size was estimated by scintigram (51%), US (33%), CT (22%) and palpation (12%). ATD treatment was used before I-131 administration by 70% of the respondents and 34% after radioiodine therapy. A low-iodine diet was given to the patients for a week (46%) or two weeks (47%) before I-131 administration. However, after treatment only 46% of the respondents continued low-iodine diet for a week.

Additional phase III multicenter clinical study was performed to investigate the efficacy, safety, and usefulness of somatostatin receptor scintigraphy using 111In-pentetreotide (MP-1727), which binds to somatostatin receptors. Forty patients were included in the study; Group A: 18 patients, gastrointestinal hormone producing tumors had been detected with conventional imaging modalities, Group B: 22 patients, no tumors had been detected with conventional imaging modalities in spite of high serum hormone levels. By comparing the results of the octreotide suppression test, 12/16 cases (75.0%) of Group A and 11/19 cases (57.9%) of Group B were assessed as "effective." By comparing the results of immunohistological examination, 5/9 cases (55.6%) of Group A and 2/4 cases (50.0%) of Group B were assessed as "effective." Severe adverse events were not observed in any of the evaluable 35 cases. MP-1727 was judged as clinically useful in 11/16 cases (68.8%) of Group A and 5/19 cases (26.3%) of group B. These results suggest that MP-1727 scintigraphy is very useful for the diagnosis and decision of the therapeutic strategy of gastrointestinal hormone producing tumors.

Phase III clinical study was performed to evaluate clinical utility of 123I-MIBG in the localization of tumors in 48 patients with tumors of sympathetic and adrenomedullary origin, diagnosed or strongly suspected. Sixteen patients had pheochromocytoma, 23 had neuroblastoma, 7 had medullary carcinoma of the thyroid, and 2 had Sipple syndrome. In 3 out of 48 patients, 123I-MIBG scintigraphy was performed twice. The clinical utility of 123I-MIBG was evaluated in 50 cases. Out of 140 lesions, 123I-MIBG scintigraphy demonstrated 51 true positive, 79 true negative, 1 false positive, and 2 false negative. Seven lesions were not evaluable. Sensitivity was 96.2%, Specificity was 98.8%, and Accuracy was 97.7%. An acquisition between 4 hrs and a day after injection was adequate for tumor detection. Neither adverse reactions nor abnormal laboratory findings were noted in relation to 123I-MIBG injections. Our study indicates that 123I-MIBG is a safe and useful radiotracer for visualization and localization of tumors of sympathetic and adrenomedullary origin.

Phase III clinical study in 78 patients with hyperparathyroidism was performed to determine clinical utility of 99mTc-MIBI in the localization of hyperfunctioning parathyroid lesions. Except slight tremor in one patient, no adverse events were reported. No abnormal changes in clinical laboratories or vital signs were noted. The clinical utility of the agent was evaluated in 70 patients. Out of 108 hyperfunctioning glands, 93 (86%) were detected with 99mTc-MIBI regardless of their histology, numbers, or location. Specifically, single or ectopic lesions were detected with high sensitivity (97% and 100%, respectively). Sensitivity in 53 glands with weight data was 79%, while 94% in 36 glands above 200 mg, which is extremely high compared to the 201T1-99mTc subtraction method. Specificity in a group of PHP patients with single adenoma who underwent surgery was 100% (63/63), though in case of coexistent thyroid disease obviously interfered parathyroid images. Our study indicates that 99mTc-MIBI is a safe and excellent agent for the localization of hyperfunctioning parathyroid tissues. Especially, the fact that 99mTc-MIBI detected ectopic glands with high specificity is a great advantage over the ultrasound or 201Tl-99mTc subtraction method.

We evaluated the safety and clinical usefulness of the same day protocol of exercise 99mTc-MIBI SPECT in 107 patients with heart diseases. No adverse event was observed except for one case of transient hypotension caused by the exercise. More than 95% of stress images and all of the rest images were judged as "Excellent" or "Good" in image quality. Overall sensitivity was 84.3% in detecting coronary artery disease, and no statistical difference was observed between the results obtained with Re-Ex and Ex-Re protocols. The examination was "Quite Effective" or "Effective" in diagnostic efficacy in 96.2% of the cases. We concluded that the same day protocol is a safe and useful method for diagnosing myocardial ischemia, which provides high image quality and valuable information.

Phase III clinical study in 136 patients diagnosed or strongly suspected of thyroid, lung/mediastinum or breast cancer was performed to determine clinical utility of 99mTc-MIBI in the localization of tumors, and the results in 135 were evaluated. Except taste peculiar in 43 patients and nausea in one, no adverse events were reported. Seven abnormal changes in vital signs and 27 in clinical laboratories were noted, which were all judged as having no or unlikely relationship to the agent. Out of 177 malignant lesions, 156 (88%) were detected with 99mTc-MIBI regardless of their histology or location. Of 6 benign tumors, 3 were detected. Fifteen sites of false positive in 11 malignant tumor patients and 5 sites in 6 patients with non-tumor disease were observed. Our study indicates that 99mTc-MIBI is a safe and excellent agent for the localization of tumors. Especially, the fact that 99mTc-MIBI detected remote metastatic lesions with high sensitivity is a great advantage over the other conventional imaging modalities.

Increased pulmonary 201TlCl (Tl) uptake during exercise has been used as a marker of multivessel critical stenosis. We studied whether pulmonary 99mTc-Tetrofosmin (TF) uptake measurement during exercise is useful as an additional indicator for the detection of coronary artery disease. Pulmonary to myocardial uptake ratio (P/M) measured by TF scintigraphy during exercise were compared with findings of coronary angiography in eighty one patients with ischemic heart disease and also P/M measured with Tl in twenty one cases. TF P/M level in the patients with triple vessel disease was higher than that in the patients with no coronary stenosis, single vessel disease and double vessel disease. However, there was no significant correlation between TF P/M and the severity of coronary artery stenosis. Inverse correlation was observed between TF P/M and left ventricular ejection fraction (LVEF) (r = 0.29, p < 0.01). TF P/M in the patients less than 50% of LVEF was significantly higher than that in the patients over 50% of LVEF (p = 0.05). TF P/M was well correlated with Tl P/M (r = 0.86). In conclusion, quantitative TF P/M during exercise was thought to be useful indicator for the evaluation of coronary artery disease.

We experienced a case of a 60 year-old man with cardiac sympathetic denervation after aortic graft replacement of ascending aorta for a dissecting aneurysm (Debakey type II). Fourteen years after pheochromocytomectomy (paraganglioma), the patient developed a severe chest pain, and admitted to the hospital for the diagnosis of dissecting aneurysm. CT scan with contrast enhancement revealed thrombosed dissecting aneurysm in the region of ascending aorta to aortic arch. Graft replacement was undergone on the same day. 123I-MIBG imaging 20 days after the operation showed severely attenuated myocardial uptake (heart to mediastinum ratio 1.19), although the MIBG imaging before the operation showed normal myocardial uptake (heart to mediastinum ratio 1.55). Heart rate variability analysis in Holter ECG showed that the power of the low frequency (LF), that of the high frequency (HF) and L/H ratio were severely decreased. MIBG and heart rate variability analysis indicated that cardiac sympathetic and parasympathetic nerve were denervated. This is the first report of cardiac sympathetic denervation after aortic vascular surgery. Clinical significance of cardiac sympathetic denervation after aortic vascular surgery is uncertain, and further investigation will be required.

The phase III clinical trial of strontium-89 chloride agent (SMS.2P) was performed in 90 patients with painful bone metastases secondary to prostate (53), breast (18) and other types of cancer (19). Some patients experienced a transient increase in pain or nausea and vomiting. However both symptoms subsided and serious side effects were not observed in any of the patients. As reported, we confirmed some abnormal changes in peripheral blood picture. A decrease in the number of white blood cells and platelets was considered to be partly a result of bone marrow suppression due to 89Sr irradiation. Pain was substantially improved after 89Sr therapy in 58% of the patients and there was some alleviation in 12%. The release from pain was accompanied by an improved quality of life for these patients including sleep patterns and morbidity. Some patients were able to resume their former life styles. Most of the improved patients experienced pain relief from days to one week following 89Sr therapy and in half cases, this remained effective for 2 or 3 months. There were even cases in which the pain relief continued over an observation period of time of clinical study.

In order to evaluate the exposure to the nuclear medicine technologists from patients who had been administrated with radiopharmaceuticals, we measured the exposure in 5 common diagnostic procedures (bone, lung, tumor scan, and brain, myocardial SPECT, n = 8 to 52) using a silicon semiconductor pocket dosimeter. We also measured the spatial dose rates at 5 cm, 50 cm, and 100 cm from skin surface of the patients (n = 10 to 21) using an ionization chamber, both 5 min after injection and right before the studies with the same procedures above. We further measured the spatial dose rate distributions around the patients in the 4 procedures (bone, renal, blood pool scan, and brain SPECT, n = 2 to 3). In results, the exposure to the technologists in each procedure was small (0.5, 0.5, 0.7, 1.6, and 0.3 muSv in each bone, lung, tumor scan, and brain, myocardial SPECT, respectively), compared with the dose limits of the medical workers. However, the dose-response relationships in cancer and hereditary effects, referred to as the stochastic effects, have been assumed linear and no threshold models; therefore, the exposure should be minimized. For this purpose, the measurements of spatial dose rates and spatial dose rate distributions were thought to be useful. The differences of these results among procedures were caused by the differences of dose distributions and physical and biological half lives of the radiopharmaceuticals. The results of the measurements in 7 consecutive weeks suggested that the direct measurement of the exposure using a high sensitive digital pocket dosimeter might result a reduced exposure to the technologists.

A series of thallium-201 (201Tl) and technetium-99m (99mTc) myocardial perfusion images with or without perfusion defects were acquired by 360 degrees arc using a triple-head camera. The vertical long, horizontal long, and short axis images of 201Tl and 99mTc with 360 degrees, 180 degrees, and opposite 180 degrees were identically reconstructed and reoriented without attenuation correction. In order to detect the detailed differences between 360 degrees (30 degrees - 390 degrees) and 180 degrees (30 degrees - 210 degrees) images, the opposite 180 degrees (210 degrees - 30 degrees) images were utilized. Opposite 180 degrees images revealed the contribution of those to the 360 degrees images. In the normal perfusion images, the CV (coefficient of variation) of the counts in 360 degrees images with 201Tl by the segments was larger than 180 degrees images. On the contrary, the CV of the counts in 360 degrees images with 99mTc was smaller than 180 degrees images. This difference, caused by the difference of photon energy, were detected mainly as the extent of counts decreasing in the deep segments in the opposite 180 degrees images. Lesion contrasts of the opposite 180 degrees images were lower than those of 180 degrees images due to distance related collimator response (the detector response of the collimated gamma camera varies with source-to-detector distance) and scatter. Therefore, lesion contrasts were more decreased in the 360 degrees images compared with those of 180 degrees images, especially in the segments of lateral and anterior walls. The differences in lesion contrasts between 201Tl and 99mTc images were mainly in the segments of inferior and posterior walls (p < 0.05). Lesion contrast was dependent on the location of the perfusion defects, reconstruction arc, and photon energy.

A 28-year-old woman was pointed out cardiomegaly and diffuse hypokinesis of left ventricle by ultrasonography in community hospital. Coronary angiography showed normal coronary artery and, left ventriculography revealed diffuse hypokinesis (LVEF 40%). She was diagnosed idiopathic dilated cardiomyopathy by myocardial biopsy and other clinical information. Myocardial scintigraphy with 201Tl. revealed dilatation of left ventricle and diffuse inhomogeneous accumulation of 201 Tl. Dynamic 123I-BMIPP SPECT image 2 minutes after injection showed BMIPP accumulation in all segment, though, static image 15 minutes after injection indicated reduced BMIPP accumulation. These findings suggested existence of the early back-diffusion in inferior segment. Early back-diffusion of BMIPP may become a marker of abnormal fatty acid metabolism in patient with dilated cardiomyopathy.

To evaluate the diagnostic accuracy of detection of angina-related coronary arteries in patients with unstable angina pectoris. Twenty patients with unstable angina pectoris underwent 123I-BMIPP scintigraphy at rest. A mean duration from last anginal attack to 123I-BMIPP scintigraphy was 408 +/- 3.2 days. Seventeen of 20 angina-related coronary territories were detected by reduced 123I-BMIPP uptake. The sensitivity and specificity for detection of angina-related coronary arteries were 85% and 95%, respectively. The decrease in myocardial uptake of 123I-BMIPP agreed with the decrease in regional wall motion by using ultrasonic echocardiography. 123I-BMIPP scintigraphy may be useful for detection of angina-related coronary artery in a routine clinical examination in patients with unstable angina pectoris.

We evaluated the clinical significance of myocardial imaging using 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy in patients with stable effort angina pectoris (SAP) and unstable angina pectoris (UAP). Thirty-three patients with SAP were studied using rest BMIPP and stress 201TlCl (Tl) myocardial scintigraphy, and 13 patients with worsening effort type of UAP were also examined using both rest BMIPP and Tl scintigraphy. We compared those BMIPP findings with myocardial perfusion images obtained with Tl and the regional wall motion determined by left ventriculography. In 45% of 282 segments of myocardial ischemia of SAP, the degree of myocardial uptake of BMIPP was concordant with that of stress Tl and the defect score of Tl was higher than that of BMIPP. On the other hand, in 32% of 62 segments of ischemia of UAP, the degree of myocardial BMIPP and Tl uptake was concordant and BMIPP defect score was higher than Tl score. In SAP, the decrease in regional wall motion agreed better with the decrease in myocardial uptake of BMIPP than that of Tl. These results suggest that myocardial ischemic regions decreased BMIPP uptake show the disturbance of fatty acid metabolism and lead to abnormal wall motions. Such ischemic regions may be clinically severe state in patients with angina pectoris.

The purpose of this study was to clarify the clinical significance of 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in patients with left ventricular pressure-overload diseases. MIBG scintigraphy was applied to 10 pts with aortic valve stenosis (AS group), 11 pts with hypertrophic obstructive cardiomyopathy (HOCM group), 17 pts with hypertrophic non-obstructive cardiomyopathy (HCM group) and 6 control cases (C group). Mean pressure gradient in AS and HOCM groups was 62 +/- 21 mmHg and 38 +/- 18 mmHg, respectively. Initial myocardial uptake of MIBG (MU) was higher in the AS (1.92 +/- 0.46%) and HOCM (2.27 +/- 0.47%) groups than those in the HCM (1.61 +/- 0.29%) and C (1.50 +/- 0.23) groups. Myocardial clearance of MIBG (MC) was higher in the AS (39 +/- 11%), HOCM (37 +/- 19%) and HCM (28 +/- 17%) groups than that in the C (14 +/- 6%) groups. Heart/mediastinum count ratio (H/M) of AS, HOCM, HCM and C groups was 1.87 +/- 0.29, 2.09 +/- 0.19, 1.98 +/- 0.26, and 2.20 +/- 0.10, respectively. In the cases of AS, positive correlation was observed between mean pressure gradient and MU (r = 0.618, p < 0.05). In conclusion, MU was increased in the case of left ventricular pressure-overload state (AS and HOCM).

The purpose of this study was to clarify the diagnostic value of identifying viable myocardium using 99mTc-Tetrofosmin scintigraphy. Twenty-one patients with chronic coronary artery disease were studied using 201Tl exercise myocardial scintigraphy with reinjection and 99mTc-Tetrofosmin exercise myocardial scintigraphy. All patients had a history of old myocardial infarction. For 99mTc-Tetrofosmin scintigraphy, 222 MBq of 99mTc-Tetrofosmin was injected during exercise, and exercise images were obtained 20 min thereafter. There hours later, 666 MBq of 99mTc-Tetrofosmin was injected at rest, and images were obtained 40 min and 220 min later. Myocardial viability in the 99mTc-Tetrofosmin scintigraphy was estimated as fill-in findings (FF) or over 50% of %RI uptake (%TF) in the rest image. Myocardial viability in the 201Tl scintigraphy was estimated as redistribution (RD), fill-in findings in the reinjection image (FR) or over 50% of %RI uptake in the reinjection image (% TL). Sixteen of the 21 patients (76%) who underwent 201Tl scintigraphy (RD 10, FR 3, %TL 3 cases) and 15 of the 21 patients (71%) who underwent 99mTc-Tetrofosmin scintigraphy (FF 11, %TF 4 cases) had viable myocardium in the infarcted area. A comparison between the 99mTc-Tetrofosmin rest images obtained 40 min after the injection and that of 220 min revealed no redistribution findings. The %RI uptake of the infarcted area in the resting 99mTc-Tetrofosmin image (47 +/- 16%) was slightly lower than that in the 201Tl reinjection image (52 +/- 16%). In conclusion, viable myocardium was as clearly identified by 99mTc-Tetrofosmin, as by 201Tl scintigraphy.

Two cases diagnosed dilated cardiomyopathy received beta-blocker therapy, and underwent 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy before and after the treatment. In case 1, symptoms and cardiac function were improved in 1 month and 4 months after the treatment (LVEF increased from 19% to 32% and 40%), and myocardial clearance of MIBG decreased from 50% to 27% and 29%. In case 2, both symptoms and cardiac function were not improved in 1 month and 3 months after the treatment (LVEF was changed from 11% to 10% and 13%), and myocardial clearance was not significantly different between before (50%) and after (1 month: 46%, 3 months: 50%) the treatment. It was indicated that myocardial clearance of MIBG might depend on the extent of the improvement of cardiac function and symptoms, and might reflect the effects of beta-blocker therapy.

We have often experienced false positive results of the stress Thallium-201 myocardial scintigraphy (TL) for the evaluation of artery bypass graft patency after coronary artery bypass surgery (CABG). The purpose of this study is to clarify the frequency and the clinical significance of this findings. Sixty-two patients undergoing coronary angiography (CAG) after CABG were studied. These patients had undergone at total of 156 bypasses (artery grafts 108, saphenous vein grafts 48, mean bypass grafts number 2.65/cases), and the mean period from CABG to TL was 41.6 +/- 34 days. The territories of stress induced ischemia were divided into 3 territories; left anterior descending (LAD), right coronary artery (RCA), and left circumflex (LCX) territories. Patency of the bypass grafts was estimated on the absence of transient perfusion defect (TPD) on TL images. The incidence of false positive results was higher in Dipyridamole TL (38%) than in Exercise TL (18%) and higher in LAD territories (38%) than in RCA (11%) and LCX (13%) territories. All false positive cases showed no evidence of chest pain and significant ST-T change during stress TL test. High incidence of false positive results of stress TL test was observed for the evaluation of artery bypass graft patency after CABG.

Discordant findings of inferior MIBG defect between SPECT and planar images were sometimes observed in the clinical studies. In this study, we compared inferior myocardial findings between planar and SPECT image of 123I-metaiodobenzyl-guanidine (MIBG) cardiac scintigraphy in 29 patients. All patients were estimated as normal in anterior accumulation of MIBG. The patients were divided into 3 groups according to the visual finding of inferior defect in the planar and SPECT image; normal group (normal inferior accumulation of MIBG both in the planar and SPECT image, N = 10), discordance group (inferior MIBG defect was only observed in the SPECT image, but was not observed in the planar image, N = 7), inferior defect group (inferior MIBG defect was observed both in the planar and SPECT image, N = 12). Inferior/anterior count ratio of SPECT and planar image were 0.96 +/- 0.11 vs. 0.97 +/- 0.05 in normal group, 0.59 +/- 0.21 vs. 0.99 +/- 0.13 in discordance group, 0.46 +/- 0.13 vs. 0.82 +/- 0.04 in inferior defect group. Liver/heart count ratio was significantly higher in the discordance group (2.07 +/- 0.49) than that in the normal (1.14 +/- 0.15) and inferior defect group (1.45 +/- 0.39). In phantom study, it has been reported that increased liver accumulation of MIBG causes artifactual inferior defect adjacent to the liver. These data indicate that increased liver/heart count ratio may cause artifactual inferior defect on MIBG SPECT image in the clinical studies. Planar image evaluation may be helpful to distinct the artifactual inferior defect on SPECT image.

The purpose of this study is to clarify whether dynamic SPECT (DECT) immediately after the injection of 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) may represent myocardial perfusion imaging. Ten patients with unstable angina pectoris (UAP), 11 patients with acute myocardial infarction (AMI) and 6 patients with non-ischemic heart disease (NIHD) were studied using BMIPP myocardial scintigraphy with DECT. DECT acquisition was started 2 minutes after the injection of BMIPP, and DECT images were obtained every three minute for 15 minutes with 3-headed gamma camera SPECT system. Additionally, static SPECT images were acquired 30 minutes after the injection of BMIPP. These SPECT images of BMIPP were compared with thallium-201 myocardial perfusion images at rest. In UAP group, early DECT images showed almost the same findings as thallium-201 images in 8 of 10 patients, and SPECT images at 30 minutes after the injection showed reduced accumulation of BMIPP compared with thallium-201 images in all patients. In AMI group, early DECT images showed the same findings as thallium-201 perfusion images in 9 of 11 patients, and SPECT images at 30 minutes after the injection showed reduced accumulation of BMIPP compared with thallium-201 images in 5 of 11 patients. These results indicate that myocardial perfusion can be evaluated in the early image using DECT, in addition to myocardial fatty acid metabolism in the delayed image.

To evaluate the myocardial uptake of beta-methyl-(123I)-iodophenylpentadecanoic acid (123I-BMIPP), nineteen patients with ischemic heart disease including left ventricular hypertrophy (mean age 63 +/- 7.8, 14 males and 5 females) underwent BMIPP myocardial scintigraphy. Myocardial uptake (MU) of BMIPP to the total injected dose was calculated from anterior view of the planar image in all subjects, and was compared with plasma glucose (BS), triglyceride (TG), and free fatty acid (FFA). It was also compared with left ventricular mass (LVM) calculated with echocardiography. MU was not related to BS, TG, and FFA, however had the positive correlation with LVM (r = 0.676, p < 0.01). Myocardial uptake per left ventricular mass (MU/LVM) had the negative correlation with LVM (r = -0.671, p < 0.01). Further studies for the significance of MU/LVM will be required.

The therapeutic response of 131I-MIBG was evaluated in 4 patients with malignant pheochromocytoma who had been treated with 131I-MIBG and followed-up over 5 years. The patients were 2 men and 2 women with ages ranging from 41 to 69 years old (mean 53 years). The primary tumors in 3 of 4 patients had been resected four to eight years before 131I-MIBG treatment. One patient was diagnosed as adrenal pheochromocytoma, and two were retroperitoneal paraganglioma. And in one patient, the resection of primary mediastinal tumor was not performed due to the adhesion to pericardium but the diagnosis of paraganglioma was obtained by biopsy of bone lesion. All patients showed the clear accumulation of 131I-MIBG in tumor on scintigraphy. The number of doses of 131I-MIBG ranged from one to three times with 3.7 GBq per administration and a cumulative activity from 3.7 to 11.1 GBq. Treatment effect was obvious in one patient with lung, bone, and lymph node metastases whose cumulated absorbed dose with 11.1 GBq of 131I-MIBG exceeded over 150 Gy. At the present time, the duration of survival since the beginning of initial 131I-MIBG therapy is over 5 yrs. The other three patients, however, showed little effects, and died with the disease in 2.6 to 4.1 years after the initial 131I-MIBG therapy. 131I-MIBG will become a promising agent for therapy in patients with malignant pheochromocytoma with high degree of accumulation.

We studied initial myocardial uptake and myocardial clearance of 123I-metaiodobenzylguanidine (MIBG) in patients with ischemic heart disease of left ventricular dysfunction and dilated cardiomyopathy. Eleven patients with ischemic heart disease of left ventricular dysfunction (IHD group), 6 patients with dilated cardiomyopathy (DCM group) and 7 control cases (control group) were studied. Heart to mediastinum activity ratio (H/M) of early and delayed image was significantly lower in the IHD and DCM groups than in the control group. Although initial myocardial uptake of MIBG showed no significant difference among three groups, myocardial clearance of MIBG was significantly higher in the IHD (35 +/- 11%) and DCM (48 +/- 13%) groups than that in the control group (19 +/- 10%). H/M of delayed image was related to the left ventricular size, initial MIBG uptake and MIBG myocardial clearance. Negative correlation was observed between MIBG myocardial clearance and left ventricular ejection fraction in all cases. In conclusion, initial myocardial uptake of MIBG were not decreased in patients with IHD and DCM. Enhanced myocardial clearance of MIBG was observed not only in patients with DCM but also in patients with IHD.

Discordance between planar and SPECT image of inferior myocardial defect on 123I-metaiodobenzylguanidine myocardial scintigraphy (MIBG) was occasionally observed in the clinical studies. The purpose of this study is to clarify the existence of artifactual myocardial defect on MIBG SPECT image. Phantom study was performed in various kinds of situation using triple gamma camera. Artifactual defect adjacent to the liver was significantly observed in the case of increased liver/heart uptake ratio more than 2:1. Artifactual defect was markedly observed in the 180 degrees than that in the 360 degrees SPECT acquisition. To avoid artifactual defect during SPECT acquisition, liver phantom was moved down to the foot direction (vanishing liver position). In this phantom position, artifactual defect adjacent to the liver was not observed on reconstructed myocardial SPECT image. The vanishing liver position was also applicable to human study. Human body was inclined to right side at an angle of 15 degrees, artifactual defect could be avoided. Further study is needed to analyze the cause of this artifactual defect and to conform the preventive method with vanishing liver position in the routine myocardial SPECT examination.

To evaluate the quantitative analysis of 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, total injected dose measured by first pass (FP) method (TFP) was compared with that measured by phantom method using an acrylic phantom in 45 patients with cardiac disease. Heart per mediastinum ratio (H/M) was compared to myocardial uptake calculated with TFP. The total injected dose measured using the phantom in which the syringe was set in depth of 3.5 cm (Tpham) was correlated with TFP (r = 0.73, p = 0.0001). When Tpham was corrected by body weight (c-Tpham), c-Tpham showed better correlation with TFP. MU calculated by TFP (MU-FP) was well correlated with MU by c-Tpham (MU-pham) (r = 0.94, p = 0.001). These results indicate that phantom method is sufficient to substitute for FP method. Though H/M was correlated with MU-FP (p < 0.001), the interpatient variation was relatively large. Then the analysis by H/M is insufficient to substitute for the myocardial uptake. It is though to be enough to use the phantom method on daily routine work, since this method is accurate and easy to quantitate the myocardial uptake of MIBG taking a short time.

Clinical utility for detection of hyperfunctioning parathyroid glands in patients with primary and secondary hyperparathyroidism (PHPT, SHPT) using 201TlCl and 99mTcO4-images was estimated in 50 patients including 18 PHPT and 32 SHPT (male; n = 31, female; n = 19, 51.5 +/- 11.1 yr). Detection of 94 hyperfunctioning parathyroid glands in 34 cases were achieved correctly by 201TlCl and 99mTcO4- images in agreement with surgical findings. Detectability of hyperfunctioning parathyroid glands was 100% in more than 1.0 g, 62.0% in more than 0.5 g and 41.5% in less than 0.5 g respectively. Ectopic parathyroid glands in two cases and a metastasis to pretracheal lymph node in one case were clearly demonstrated. Our results show that parathyroid scintigraphy using 201TlCl and 99mTcO4- as well as 131I or 123I is useful and safe method for preoperative detection of hyperfunctioning parathyroid glands.

Radioiodine, 131I, has been used for treatment of hyperthyroidism and metastases of well differentiated thyroid carcinoma since 1942. The use of 131I to treat hyperthyroidism and metastatic foci of thyroid cancer is one of the least invasive and most effective methods since the ionization produced by beta rays of 131I and it's high target-to-nontarget ratio are suitable. The feature of therapy with 131I on hyperthyroidism has a slow improvement of symptom, a high incidence of hypothyroidism, and an exact therapeutic effect. And, there is no significant difference between the patients with late-onset hypothyroidism and euthyroidism after 131I-therapy in the pretreatment factors, such as thyroid hormone levels, thyroid weight, 131I administration dose, and absorbed dose and also in the course of follow-up studies. On the treatment of metastases of thyroid cancer with 131I, it is very effective for the patients with fine or occult type of pulmonary metastases on chest XP, who are younger than 40 years old. On the other hand, the response to bone metastases of 131I therapy is limited to only a part of tumors and/or temporally in most cases though high grade of 131I accumulation is seen on scintigram. Both surgery and a curative dose of external irradiation should be combined with radioisotope therapy for the patients of bone metastases.

The correlation of absorbed doses of tumors in 18 patients of differentiated thyroid carcinoma with distant metastases, who were treated by 131I and followed over 5 years, with their outcome were analyzed and the clinical significance of determination of absorbed dose was discussed. Radioactivities of 131I in the tumors were measured by using SPECT at the time of therapy. Absorbed dose was calculated based on the MIRD equation. Outcome of 8 patients were evaluated as good and their absorbed dose was 10-630 Gy with 2-22 g of tumor volume, 1.2-3.5 days of effective half life (EHL) and follow-up term was 8.6 +/- 0.9 years. The absorbed dose of 10 patients whose outcome were evaluated as poor, was 5-81 Gy with 7-215 g of tumor volume, 1.3-5.3 days of EHL and follow-up term was 5.6 +/- 2.5 years. The initial treatment seemed to be important for 131I therapy, since the absorbed doses in the following therapy became reduced. When the absorbed dose of the tumor exceeded over 94 Gy at initial treatment, good clinical courses were obtained. These results indicate that the quantitative SPECT for 131I therapy is clinically valid and that the calculated absorbed doses correlate well with outcome of the patients.

A phase III clinical study of 131I-metaiodobenzylguanidine (131I-MIBG) was performed in 66 patients with tumors of sympathetic and adrenomedullary origin, including 32 patients with suspected pheochromocytoma, 25 with suspected neuroblastoma, 7 pre- or postoperative medullary carcinoma of the thyroid and each with carcinoid and suspected Sipple's syndrome. A total of 150 sites which were confirmed for presence (72 sites) or absence (78 sites) of tumors were examined on 131I-MIBG scintigrams. True positive ratio of the scintigraphy was 84.7% (61/72) and true negative ratio was 94.9% (74/78). Positive scintigraphy was obtained in 86.5% (32/37) of pheochromocytoma, 78.6% (22/28) of neuroblastoma and 100% (6/6) of medullary carcinoma of the thyroid. Accumulation of 131I-MIBG was seen in 16.8% of normal adrenal glands. Neither adverse reactions nor abnormal laboratory findings were noted in relation to 131I-MIBG injections. Our study indicates that 131I-MIBG is a safe and clinically useful radiotracers for the visualization and localization of tumors of sympathetic and adrenomedullary origin.

We have studied the follow-up of thyroid function in the patients with late-onset hypothyroidism and euthyroidism after I-131 therapy of hyperthyroidism. Thirty three patients who did not need the thyroid treatment until ten years after I-131 therapy were classified as euthyroid group. And eleven patients who needed the thyroid supplement of thyroid hormone for late-onset hypothyroidism were classified as hypothyroid group. Patients in both groups who required only a single dose of I-131 for successful treatment of hyperthyroidism had similar age, gland size, 24 hour I-131 uptake, pretreatment serum T3 uptake level and T4 concentration, and I-131 treatment dose. Subclinical hypothyroidism occurred in 28.6% of euthyroid group and 66.7% of hypothyroid group four months after I-131 therapy. The levels of T3 were recovered to higher than normal range at 6 months in euthyroid group, while the levels of T3 were kept within the normal range in the seventy percent of hypothyroid group. Patients who were still lower in the level of T3 uptake than normal range at 6 months had a higher incidence of late-onset hypothyroidism. Our observation showed no significant difference in the course of follow-up studies after I-131 therapy between the patients with late-onset hypothyroidism and euthyroidism.

I-123 Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic neuronal endings. Sympathetic neuronal function in 10 patients with cardiomyopathy under stable state were studied by using MIBG and Tl-201 (Tl) SPECT images with 50% cut off level. For myocardial imaging MIBG and Tl were simultaneously injected and collected (dual injection and dual collection mode; Dd mode). Four hours delayed images were also collected. Three types of abnormal findings were noted in MIBG images in combination with Tl images. 1) Enhancement of regional MIBG washout with otherwise normal MIBG and Tl uptake in infero-lateral wall were noted in 5 patients with history of congestive heart failure (Pathophysiologically acceleration of regional sympathetic neuronal function was suspected. Mean washout ratio is 63 +/- 7% vs. 45 +/- 10% in normal region). 2) In 3 patients with dilated cardiomyopathy increase of MIBG/Tl (M/T) ratio was noted in basal septal wall (Sympathetic neuronal function is abnormally accelerated in the region with depressed coronary perfusion. Exaltation of regional sympathetic neuronal function was suspected. Mean M/T ratio is 1.6. Tentative normal range is from 0.8 to 1.20). 3) In 2 patients with dilated cardiomyopathy under severe congestive heart failure defects of MIBG uptake with normal Tl uptake were noted (Sympathetic neuronal function was depleted in spite of normal coronary perfusion. Depletion of myocardial catecolamine was suspected. M/T ratio is 0.75 and 0.7 respectively). Heterogeneous abnormality of sympathetic neuronal function was noted in MIBG images. This findings corresponded to report about heterogeneous myocardial catecholamine concentrations in hearts of recipients of transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)