Kazuki Fukuchi

Distribution of cocaine recognition sites in rat brain: in vitro and ex vivo autoradiography with [125I]RTI-55.

The distribution of binding sites of [125I]RTI-55 (3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester), a phenyl tropane analog of cocaine, and the selective labeling of the dopamine transporter (DAT) were studied by in vitro and ex vivo autoradiography in the rat whole brain. Recent evidence has shown that RTI-55 binds to not only DAT but also serotonin transporter (5HTT). In the present study, in vitro autoradiography revealed that [125I]RTI-55 bound to the olfactory tubercle, the caudate putamen, the accumbens nucleus, the midline and lateral geniculate nuclei of the thalamus, the hypothalamic nuclei, the substantia nigra compact part, the subthalamic nucleus, the ventral tegmental area, the superior colliculus, the dorsal raphe nucleus, and the facial nucleus. Further, in the presence of clomipramine, a selective ligand for 5HTT, [125I]RTI-55 binding was remarkably inhibited in the midline and lateral geniculate nuclei of the thalamus, the hypothalamic nuclei, the superior colliculus, the dorsal raphe nucleus, and the facial nucleus, while [125I]RTI-55 binding remained in the olfactory tubercle, the caudate putamen, the accumbens nucleus, the substantia nigra compact part, the subthalamic nucleus, and the ventral tegmental area. These findings suggest that [125I]RTI-55 binds to 5HTT in the former areas and to DAT in the latter areas. It is therefore concluded that RTI-55 is a suitable ligand for studying the action of cocaine in whole brain regions, including the thalamus, the hypothalamus and the dorsal raphe nucleus, regions in which cocaine is thought to act evoking several neurological effects, e.g., analgesia and elevation of adrenocorticotropic hormone. DAT was also labelled selectively both in vitro and in vivo using [125I]RTI-55 combined with clomipramine. Therefore, radiolabelled RTI-55, combined with unlabelled clomipramine, which displaces its binding to 5HTT, also appears to be suitable for the selective imaging of DAT in vivo.

Increased bone mineral turnover without increased glucose utilization in sclerotic and hyperplastic change in fibrous dysplasia.

Fibrous dysplasia is a benign bone disorder. It is diagnosed by distinctive X-ray radiography, CT, and MRI findings. Although bone scintigraphy helps to identify the tumor origin according to accelerated bone turnover, the glucose metabolism in fibrous dysplasia has not yet been investigated. We reported a case of fibrous dysplasia in craniofacial bone which showed signs of the acceleration of bone mineral turnover without elevated glucose utilization by Technetium-99m-HMDP SPECT and Fluorine-18-FDG PET. We concluded that the growth of fibrous dysplasia needed the acceleration of bone mineral turnover without an increase in glucose metabolism.

Renal Function in Patients with Abdominal Aortic Aneurysm

Aims: Renal dysfunction occurs occasionally after the repair of abdominal aortic aneurysm (AAA), and preoperative renal function is considered as one of the potential causes. The present study was designed to evaluate and compare renal function and risk factors of AAA patients with those of hypertensive patients. Methods: We prospectively examined 95 patients with AAA and 72 patients with essential hypertension (HT) without other cardiovascular diseases (CVD). Renal function, urinary albumin excretion (UAE) and renal scintigraphy were compared. Kidney size was calculated using ultrasonography. Results: Serum creatinine and creatinine clearance in AAA patients was worse than in HT patients. Smoking status was more apparent in AAA patients. Renal artery stenosis occurred in 8 patients with AAA. Renal scintigraphy showed normal function in 19%, hypofunction in 69% and severe dysfunction in 12% of the AAA patients, and normal function in 42% and hypofunction in 58% of the HT patients (p < 0.0001). Multivariate linear regression analysis showed that renal function was related to age, UAE, CVD, smoking status and kidney size for all patients, UAE, CVD, smoking status and kidney size for AAA patients, and age and kidney size for HT patients. Conclusion: Renal function of AAA patients was worse than HT patients without other CVD. The risk factors for renal dysfunction were different between AAA and HT patients. These preoperative conditions may relate to the postoperative renal dysfunction seen in AAA patients.

Myocardial imaging with 123I-BMIPP in patients with congestive heart failure

First, we studied the diagnostic utility of myocardial imaging with 123I-BMIPP (BMIPP), a 3-methyl-branched fatty acid analog, in patients with various types of cardiomyopathy and left ventricular dysfunction (ejection fraction below 40%) by comparing with myocardial flow tracer imaging. The incidence of a dissociation between myocardial BMIPP and 201Tl distributions (BMIPP< 201Tl) as a marker of metabolic abnormality in viable tissue varied considerably among various heart diseases. Patients with ischemic cardiomyopathy and the dilated form of hypertrophic cardiomyopathy had a higher incidence while those with idiopathic dilated, alcoholic and hypertensive cardiomyopathy had a lower incidence. These results suggest that the marked difference between ischemic and idiopathic dilated cardiomyopathies may contribute to the differential diagnosis between these two diseases which are main basic abnormalities in congestive heart failure. Second, we investigated the relationship between myocardial BMIPP uptake and ventricular stress in patients with right ventricular pressure overload due to pulmonary hypertension. Myocardial BMIPP uptake in the right ventricle estimated by referring to uptake in the left ventricle showed a significant correlation with mean pulmonary artery pressure (mPAP) and no significant difference with myocardial 99mTc-sestamibi uptake in the 15–81mmHg mPAP range. These results suggest that myocardial utilization of free fatty acid may be preserved in the presence of higher ventricular wall stress.

Correlation of sequential MR images of microsphere-induced cerebral ischemia with histologic changes in rats.

OBJECTIVE To determine the time course of changes in MRI findings of multiple cerebral microembolism, the authors induced experimental multiple microinfarctions in rats using microspheres and then examined sequential MRI and histopathologic findings. The authors also evaluated how the amount of injected embolic materials affected the findings. METHODS The authors injected 25-microm microspheres (range, 2000-8000 gm) into the unilateral internal carotid arteries of rats. The animals were assessed by MRI and histopathology at 1 day or 8 days after embolization. RESULTS One day after embolization, multiple high-intensity areas on T2-weighted images were related to the number of injected microspheres and were associated with regions of cerebral edema on histopathologic specimens. On day 8, the high-intensity areas on T2-weighted images observed on day 1 were markedly diminished in the groups receiving up to 6000 microspheres. In the group injected with 8000 microspheres, however, the high-intensity areas were less diminished, and these areas were significantly larger than in the other groups (P < 0.05). CONCLUSIONS The MRI features of cerebral ischemia or infarction induced by microsphere embolism vary depending on the number of injected microspheres. Recovery from acute cerebral embolism has a threshold based on ischemic cell volume.

Comparison of dual-isotope acquisition of 201Tl and 99Tcm-tetrofosmin for the detection of ischaemic heart disease and determination of the optimal imaging time of 99Tcm-tetrofosmin.

Comparative studies of thallium-201 (201Tl) and 99Tcm-tetrofosmin for the detection of ischaemic heart disease (IHD) have previously been reported. These 201Tl and 99Tcm-tetrofosmin studies were usually performed separately with different exercise loads at an interval of several days. Here, we used a dual-isotope technique with exercise myocardial SPET (single photon emission tomography) in 17 patients with IHD and 10 patients with normal coronary arteries. The triple-energy window (TEW) method was applied for cross-talk correction. SPET imaging was performed at 10 and 70 min (S1 and S2) after the injection of 99Tcm-tetrofosmin (222 MBq) and 201Tl (74 MBq) at peak exercise to determine the optimal imaging time of 99Tcm-tetrofosmin. The S2 value was obtained 35 min after the subject drank a glass of milk to accelerate hepatobiliary clearance. Twenty-five minutes after S2, 37 MBq of 201T1 were reinjected at rest and SPET imaging (S3) was performed. Immediately after S3, 666 MBq of 99Tcm-tetrofosmin were reinjected and SPET imaging (S4) was performed 50 min later. Representative short and vertical long axis tomograms were divided into 17 segments. Each segment was assessed using a 4-point scoring system. The defect score was defined as the sum of each segmentai score. The defect scores for imaging at exercise were 14.3 ± 11.4 for 201Tl at Sl, 11.4 ± 8 for 99Tcm-tetrofosmin at Sl and 9.7 ± 9.8 for 99Tcm-tetrofosmin at S2 (P < 0.01), respectively. The washout rate of 99Tcm-tetrofosmin for the first hour was 15.5 ± 7.3% and 11.8 ± 7.7% (P < 0.01), respectively, for the normal and ischaemic segments. The image quality of 201Tl at SI was almost equivalent to that of 99Tcm-tetrofosmin at S1/S2. The overall sensitivity and specificity for the detection of ischaemia was 94% and 82% for 201Tl at SI, 89% and 86%, for 99Tcm-tetrofosmin at SI, and 88% and 95% for 99Tcm-tetrofosmin at S2, respectively. The overall accuracy was 86%, 88% and 92%, respectively. The myocardial viability score was 7.4 ± 7.1 for 201Tl at S3 and 5.8 ± 7.0 for 99Tcm-tetrofosmin at S4 (P < 0.01). The results indicate that the diagnostic accuracy of 99Tcm-tetrofosmin for myocardial ischaemia is almost equivalent to that of 201Tl as assessed by dual SPET imaging, and that the optimal imaging time for 99Tcm-tetrofosmin is within 10–35 min (SI) after exercise.

The Cutoff Value of Aldosterone-to-Renin Ratio for the Diagnosis of Primary Aldosteronism in Patients Taking Antihypertensive Medicine

Background. Primary aldosteronism (PA) may account for as much as 6–20% of cases of refractory hypertension referred to hypertension clinics. Because antihypertensive agents affect the physiologic renin-angiotensin-aldosterone system, screening diagnostic tests for PA are generally performed after antihypertensive agents are discontinued. However, such tests can be dangerous for patients with severe hypertension or other cardiovascular complications. However, a reliable cutoff value for the aldosterone-to-renin ratio (ARR) has not been established, especially for Asians, including the Japanese. Method. Fifty-five consecutive patients with clinically suspected PA were evaluated from July 10, 2001, to March 1, 2005, at the National Cardiovascular Center in Japan. Every referred patient was screened prospectively for PA with the ARR at the outpatient clinic. The patients tested continued to be treated with a variety of antihypertensive agents. We reviewed the sensitivity, specificity, and accuracy of the ARR without modifying the antihypertensive agents. The diagnosis of PA was established with the results of both abdominal computed tomography and adrenal scintigraphy. Results. Of the 55 patients, 27 were found to have PA, including adrenal adenoma (n = 18) and bilateral adrenal hyperplasia (n = 9). The mean ARR of patients with PA was significantly higher than that of patients without PA. By assuming a cutoff value of the ARR ≥ 69 calculated from the receiver operating characteristics curve, the highest sensitivity (81%), specificity (82%), positive-predictive value (81%), and negative-predictive value (81%) were obtained. Conclusion. The data suggest that an ARR ≥ 69 strongly indicates PA in Japanese patients with hypertension being treated with antihypertensive agents.

Contribution of hypoxia to the development of cardiomyopathy in hamsters

OBJECTIVE It has been hypothesized that microvascular spasms cause cardiomyopathy. To elucidate the contribution of hypoxia to the development of cardiomyopathy, the newly-developed hypoxia tracer, Tc-99m nitroimidazole, was applied to detect myocardial hypoxia in a hamster model. METHODS Tc-99m nitroimidazole (180 MBq) and I-125 iodoantipyrine (370 kBq) were injected into cardiomyopathic Syrian hamsters or control hamsters at age 10, 25, and 40 weeks (n = 6 in each group). The myocardial uptake of Tc-99m nitroimidazole was measured and dual tracer autoradiography was performed. RESULTS Histologic study revealed that the cardiomyopathic hamsters at age 10, 25 and 40 weeks were in the myocytolytic stage, the fibrotic and healing stage, and the hypertrophy and dilatation stage, respectively. Tc-99m nitroimidazole uptake was significantly greater in the cardiomyopathic hamsters than in the controls at age 25 weeks (cardiomyopathic hamsters, 33.3 +/- 4.7% g dose/g; control, 25.2 +/- 3.1), whereas there were no significant differences between both strains at age 10 and 40 weeks. The quantified concentration of I-125 iodoantipyrine in the cardiomyopathic hamster at age 40 weeks was significantly lower than that in the controls. When the Tc-99m nitroimidazole uptake was normalized by I-125 iodoantipyrine concentrations, the cardiomyopathic hamsters at age 25 and 40 weeks showed significantly greater uptake than the controls. CONCLUSION The myocardium in cardiomyopathic hamsters was hypoxic at the fibrotic and healing stage and may be hypoxic at the hypertrophy and dilatation stage. This may contribute to the development of cardiomyopathy.

Efficacy of screening for primary aldosteronism by adrenocortical scintigraphy without discontinuing antihypertensive medication.

BACKGROUND Recently, it has been proposed that discontinuation of antihypertensive medications is not necessarily essential for the measurement of plasma aldosterone-to-renin ratios. We examined the efficacy of adrenocortical scintigraphy performed without modification of antihypertensive medications. METHODS A retrospective study was conducted on 119 patients, in whom functional tests, anatomic studies, and adrenocortical scintigraphy were replete. Interrelationship among these was studied. The patients tested were being treated with antihypertensive medications from several classes including angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers, diuretics, and spironolactone. RESULTS Significantly higher percentage of scintigraphy positive patients had plasma aldosterone-to-renin ratio of greater than 25:1. Positive rate for adrenal nodules by anatomic studies was significantly higher in the scintigraphy positive patients than in the scintigraphy negative patients. Finally, the percentage of patients who underwent adrenalectomy was higher in the scintigraphy positive patients than in the scintigraphy negative patients. CONCLUSIONS We conclude that adrenocortical scintigraphy is a valid evaluation tool for primary aldosteronism and that the discontinuation of antihypertensive medications is not a requirement for this test.

Paraganglioma seen with FDG dual-head gamma camera coincidence imaging after false-negative results of I-123 MIBG imaging.

False-negative results of an iodine-123 MIBG study were found in a patient with recurrent extra-adrenal paraganglioma. F-18 fluorodeoxyglucose (FDG) dual-head gamma camera coincidence imaging clearly showed abnormal accumulation in the tumor, which was confirmed with magnetic resonance imaging (MRI).