Assessment of dopamine metabolism in brain of patients with dementia by means of18F-fluorodopa and PET

By means of positron emission tomography (PET) and¹⁸F-fluorodopa (FDOPA), a study was initiated to analyze the cerebral dopamine (DA) metabolism of 32 subjects including those with AD/ SDAT and vascular dementia (VD, multi-infarct type). A semiautomated irregular ROI drawing routine to identify the striatum was developed that interactively defined the PET threshold pixels referring to the count histograms and location of the corresponding pixels. A comparative study by five examiners showed significant improvement in the area size definition and count linearity particularly for low contrast objects. The graphical plot was employed to calculate the FDOPA influx rate (Ki) for the ROI data with cerebellar radioactivity as an input function. The striatal Ki value was found to be relatively stable and did not show signs of a significant age-related change. The vascular patients had smaller Ki to the striatum than the aged control. Although the mean Ki of AD/SDAT was almost compatible with that of age-matched normals, their Ki was more scattered with higher and lower Ki cases. The multiple regression analysis revealed that the Ki could be predicted by age and the mini-mental state (MMS) performance (r² = 0.590, p < 0.01 for AD/ SDAT, r² = 0.401, and p < 0.05 for VD). MMS was found to be a more dominant factor than age. We conclude that dopamine metabolism became disturbed as dementia became progressively severe.     

FDG-PET for the evaluation of tumor viability after anticancer therapy

To evaluate positron emission tomography with¹⁸F-fluorodeoxy glucose (FDG-PET) as an diagnostic tool to determine tumor viability after anticancer therapy, fourteen patients were examined by FDG-PET after the end of the treatment. The lesions with residual viable tumor cells showed higher uptake of FDG than surrounding normal soft tissue. The lesions, in which tumor viability was lost or very low, showed higher uptake of FDG in four cases and similar uptake to normal soft tissue in three cases. The residual increased uptake of FDG was considered to be caused by remaining tumor cells and/or inflammatory reaction to anticancer treatment. FDG-PET after anticancer treatment should be interpreted by considering the reaction due to the treatment and the partial volume artifact of PET caused by the limited spatial resolution.     

Delayed L-phenylalanine infusion allows for simultaneous kinetic analysis and improved evaluation of specific-to-nonspecific fluorine-18-dopa uptake in brain.

The accumulation of 3-O-methyl-6-[18F]fluoro-L-DOPA (18F-30M-DOPA) in the brain from the circulation is responsible for most of the nonspecific background during 18F-DOPA positron emission tomography scanning. To increase the sensitivity of 18F-DOPA for imaging presynaptic dopamine systems, we took advantage of 18F-30M-DOPA's rapid clearance from the brain (T1/2 approximately 15-20 min). The infusion of the unlabeled amino acid L-phenylalanine, starting 75 min after 18F-DOPA administration, prevents 18F-30M-DOPA entrance into the brain through competition at the large amino acid transport system of the blood brain barrier. This method produces high specific-to-nonspecific contrast images of 18F accumulation beginning 15-30 min after onset of amino acid infusion and better sensitivity to small changes in 18F-DOPA uptake while still allowing for kinetic analysis of the data in the early time points. Kinetic and anatomical data were found to be strongly correlated.     

Significance of myocardial uptake of iodine 123-labeled beta-methyl iodophenyl pentadecanoic acid: Comparison with kinetics of carbon 11-labeled palmitate in positron emission tomography

Background

A radioactively labeled beta-methyl branched fatty acid analog,¹²³I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP), has been developed to probe regional myocardial fatty acid metabolism. However, the significance of BMIPP uptake in the myocardium remains unclear.

Methods and Results

To evaluate the significance of BMIPP uptake, single-photon emission computed tomography was performed 30 minutes after injection of BMIPP, and²⁰¹Tl-labeled single-photon emission computed tomography was taken on a separate day in 10 patients. Findings of BMIPP and²⁰¹Tl-labeled imaging were compared with the data obtained from positron emission tomography with¹¹C-labeled palmitate. The BMIPP uptake (percent of maximum) was significantly correlated with the early uptake (percent) and delayed uptake (percent) of¹¹C-labeled palmitate (r=0.659 andr=0.687, respectively) (p<0.01 each), whereas it was not significantly correlated with the residual fraction (r=0.205) or the clearance half-time of the early component (r=0.138) of¹¹C-labeled palmitate as a marker of β-oxidation of the fatty acid.

Conclusions

These data indicate that, although the myocardial uptake of BMIPP may not directly reflect β-oxidation of fatty acids, its uptake may reflect both regional myocardial blood flow and fatty acid extraction.     

Quantifying regional cerebral blood flow with N-isopropyl-p[123I]iodoamphetamine by ring-type single-photon emission computed tomography: Validity of a method to estimate early reference value by means of regional brain time-activity curve

A more accurate quantitative method for the measurement of regional cerebral blood flow (rCBF) with the microsphere model and N-isopropyl-p-[¹²³I]iodoamphetamine (¹²³I-IMP) and ring-type single-photon emission computed tomography (SPECT) was developed. Continuous withdrawal of arterial blood was carried out for 5 minutes after the injection. Static SPECT data were acquired from 25 min to 55 min. To estimate reconstructed images at 5 min, total brain count collections and one minute SPECT studies were performed at 5, 20, and 60 min. Quantitative values for rCBF were calculated from short time SPECT images at 5 min (rCBF), static SPECT images corrected by total brain counts (rCBF_ct) and those corrected by reconstructed counts on short time SPECT images (rCBF_Cb). Practically, rCBF_Cb is calculated by using reconstructed counts of regions of interest placed in the same position as static SPECT and short time SPECT at 5, 20, 60 min. Although there was good correlation between rCBF and rCBF_Ct (r = 0.69), rCBF_ct tended to be underestimated in high flow areas and overestimated in low flow areas. A better correlation was observed between rCBF and rCBF_Cb (r = 0.92). The overestimation and underestimation observed in rCBF_Ct was considered to be due to the correction method with a total cerebral time activity curve, because the kinetic behavior of¹²³I-IMP was different in each region.     

Autoradiographic analysis of [14C]deoxy-D-glucose in thyroid cancer xenografts: A comparative study with pathologic correlation

An experimental model of thyroid cancer was prepared for evaluating the accumulation of [¹⁴C]deoxy-D-glucose ([¹⁴C]DG) in thyroid cancer xenografts (AC2). A continuous cell line established from a biopsy specimen of a metastatic thyroid carcinoma possessed the ability to synthesize the cellular protein without increase in cell division after adding bovine TSHin vitro. The histological sections of the xenografts resected from the¹³¹I treated nude mice mainly consisted of structures showing follicular and trabecular growth. Immunohistochemically the cytoplasm of the tumor cells was positive for human thyroglobulin(hTg). These observations provide strong evidence that the AC2 cell originates in the thyroid follicular epithelium. By comparing autoradiographic accumulation patterns of [¹⁴C]DG and histopathological examinations, it was found that the uptake of [¹⁴C]DG was higher in the granulation tissues surrounding necrosis than in viable tumor cells of trabeculary growing and follicle forming tissues. It is suggested that the degree of [¹⁴C]DG content reflects not only tumor cell viability and proliferation but also the inflammatory and degenerative reaction accompanying tumor cell growth.     

Analysis of scintigrams by singular value decomposition (SVD) technique

The singular value decomposition (SVD) method is presented as a potential tool for analyzing gamma camera images. Mathematically image analysis is a study of matrixes as the standard scintigram is a digitized matrix presentation of the recorded photon fluence from radioactivity of the object. Each matrix element (pixel) consists of a number, which equals the detected counts of the object position. The analysis of images can be reduced to the analysis of the singular values of the matrix decomposition. In the present study the clinical usefulness of SVD was tested by analyzing two different kinds of scintigrams: brain images by single photon emission tomography (SPET), and liver and spleen planar images. It is concluded that SVD can be applied to the analysis of gamma camera images, and that it provides an objective method for interpretation of clinically relevant information contained in the images. In image filtering, SVD provides results comparable to conventional filtering. In addition, the study of singular values can be used for semiquantitation of radionuclide images as exemplified by brain SPET studies and liver-spleen planar studies.     

In vivo kinetics of99mTc labeled recombinant tissue plasminogen activator in rabbits

Our previous studies demonstrated that^99mTc labeled recombinant tissue plasminogen activator (rt-PA) retained high affinity with fibrinin vitro but showed unexpectedly low uptake in fresh thrombiin vivo. The present study was performed to determine thein vivo kinetics of radiolabeled t-PA in the rabbit. Sequential images and blood samples after the intravenous administration of^99mTc labeled rt-PA in thrombus-bearing rabbits were taken. The radioactivity and immunological level of t-PA and PAI-1 in the solution eluted to each fraction by gel permeation chromatography were measured by means of a well scintillation counter and enzyme-linked immunosorbent assay (ELISA). Most of the radioactivity was eluted in the fraction (Fr. 7) of larger molecular weight than that (Fr. 9) of intact t-PA. The level of intact rt-PA was increased with a regimen involving the preadministration of cold rt-PA which was followed by the administration of hot rt-PA. The level of PAI-1 in plasma showed an increased rebound 15 minutes after the intravenous injection. These results suggest two possible reasons why rt-PA retains high affinity with fibrinin vitro, once radiolabeled, but was ineffective in delineating fresh thrombi with a gamma camera: 1) some plasma components such as PAI-1 combine with circulating radiolabeled rt-PA and form a larger molecule immediately and/or 2) radiolabeled rt-PA is modulated as a consequence of the radiolabeling and forms a larger molecule than intact rt-PA.     

Optimal dose of injection in activation study with O-15 water and PET

In activation studies with the bolus method for O-15 water and PET, the radiotracer concentration may reach the limits of the system in terms of dead time correction and accidental coincidence. To obtain the optimal injection dose of O-15 water, we performed a normal volunteer study to evaluate the relationship between the injected dose and the radioactivity concentration in the brain and a phantom study to evaluate the performance of the PET scanner (PCT3600W) under high count rate conditions and the effect of averaging on the signal to noise ratio for the PET images. A linear relationship was noted between the injected dose (normalized for each body weight: x) and the mean radiotracer concentration in the brain measured by PET (y) (y = 2.52 + 30.1x, n = 64, r = 0.87, p < 0.001). The percent error in the measurement of radioactivity with PET was within ± 5% in the 100 to 2000 nCi/m/ (3.7–74 KBq/mZ) range. Below 100 nCi/mZ (3.7 KBq/mZ), the percent error increased due to the rapid increase in noise in the reconstructed images. Over 1000 nCi/ mZ (37 KBq/mZ), on the other hand, the noise was almost unchanged. With our PET scanner, the optimal range of the radiotracer concentration in the brain is below 1000 nCi/mZ (37 KBq/mZ), corresponding to an injection dose of 33 mCi (1.22 GBq)/60 kg body weight. With the same total dose, the increment of number of repeated measurements for averaging provided the better signal to noise ratio. In designing a paradigm for an activation PET study, the injection dose and the number of repeated measurements for averaging should be considered.     

Noninvasive identification of left main and three-vessel coronary artery disease by thallium-201 single photon emission computed tomography during adenosine infusion

Advanced coronary artery disease, defined as left main or three-vessel coronary disease, was identifiable noninvasively by means of adenosine Tl-201 single photon emission tomography. Among 75 consecutive patients with angiographically documented coronary artery disease, there were 11 patients with the presence (group 1) and 64 patients with the absence (group 2) of advanced coronary artery disease. The lung-to-heart ratio (L/H ratio) of Tl-201 uptake was calculated as the fraction of average Tl-201 counts per pixel in the lung divided by those in the myocardium. The left ventricular dilation ratio (LVDR) was determined as a ratio of left ventricular cavity size in the early image to that in the delayed image. The patients in group 1 had more defects (2.3 ± 0.6 seg. vs. 0.9 ± 0.7 seg., p < 0.001), ahigher L/H ratio (35 ± 4% vs. 28 ± 5%, p < 0.001) and a higher LVDR (1.13 ± 0.04 vs. 1.06 ± 0.04, p < 0.001) than those in group 2. The diagnostic accuracy of the identification of advanced coronary artery disease was 89% by perfusion defects, 68% by L/H ratio and 81% by LVDR. Stepwise discriminant analysis revealed that LVDR (F = 36.2, p < 0.0001) and perfusion defects (F = 8.9, p < 0.004) were the significant and independent discriminators of advanced coronary disease. Identification of patients with left main or three-vessel coronary disease was enhanced by additional analysis of cavity dilation of the left ventricle and increased Tl-201 activity in the lung.     

Impaired hepatic function in segmental biliary obstruction demonstrated with a receptor-binding radiotracer

A patient with cholangiocarcinoma underwent left-sided cholangiojejunostomy, and hepatic functional imaging with a receptor-binding radiotracer and SPECT was performed to evaluate the distribution of functional reserve. It revealed decreased accumulation in the regions with residual dilatation of the intrahepatic bile ducts, indicating several kinds of focal damage in hepatic function caused by segmental biliary obstruction. The radioligand may be useful in assessing regional hepatic function, and the high spatial resolution provided by SPECT appears to play an important role for this purpose.     

Thallium-201 reinjection images can identify the viable and necrotic myocardium similarly to metabolic imaging with glucose loading18F-fluorodeoxyglucose (18FDG)-PET

We compared the usefulness of¹⁸F-fluorodeoxyglucose (¹⁸FDG)-PET with glucose loading and thallium-201 (²⁰¹Tl) reinjection imaging for determining the viability of the myocardium in 21 patients with an old anterior myocardial infarction. We obtained transaxial views during²⁰¹T1 reinjection imaging performed 10 minutes after post-exercise injection of 37 MBq²⁰¹Tl. PET imaging with 75 g oral glucose loading was performed 60 min after injection of 148 MBq of I8FDG. Wall motion was evaluated by echocardiography. Excellent¹⁸FDG-PET images were obtained in 19 of 21 subjects in whom plasma glucose levels were below 251 mg/d/. The results of²⁰¹Tl reinjection imaging and¹⁸FDG-PET imaging were in agreement in 20 of the 21 subjects. Echocardiography demonstrated hypokinesis or akinesis in segments identified as abnormal in imaging studies. Our results showed that²⁰¹Tl reinjection imaging identified the viable and necrotic myocardium similarly to metabolic imaging obtained by¹⁸FDG-PET with glucose loading.     

Quantitative myocardial perfusion single-photon emission computed tomographic imaging: Quo vadis? (where do we go from here?)

Quantitative myocardial perfusion single-photon emission computed tomography can be improved further by technical advancements that are imminent in the clinical setting. These improvements are directed toward two main goals: (1) increasing the accuracy that the myocardial count distribution from tomographic slices represents the true tracer concentration and (2) increasing the accuracy of extracting this myocardial count distribution for quantitative analysis. Once these advancements are fully validated and implemented clinically, the clinical value of these cardiac diagnostic tests will be enhanced by increased accuracy of detecting and characterizing myocardial hypoperfusion and coronary artery disease.     

Value of thallium-201 early reinjection for assessment of myocardial viability

To assess the efficacy of early reinjection forpredicting post intervention improvement in thallium-201 (Tl) uptake and regional wall motion, we reinjected a small dose of Tl following post-stress imaging and obtained reinjection early images (10 min after early reinjection) and reinjection delayed images (3 hr afterwards) in 40 patients who were referred to us for revascularization (group I). Twenty-nine patients in group I also underwent conventional stress-redistribution Tl scintigraphy (group II). Conventional stress-redistribution Tl scintigraphy was repeated after intervention. Contrast left ventriculography was performed before and after intervention and changes in regional wall motion were assessed in 22 of 40 patients. In group I, the predictive value for improvement and no improvement (the accuracy) of reinjection early images in perfusion was 83%, while that of reinjection delayed images was 91%. Furthermore, the accuracy of reinjection early images in regional wall motion was 80%, while it was 91% for reinjection delayed images. In group II, the accuracy in perfusion was 78% and the value in regional wall motion was 70%. Both accuracy in perfusion and in regional wall motion obtained from reinjection delayed images were significantly higher than the values in group II (p < 0.05). These data suggest that early reinjection is useful for predicting postintervention thallium uptake and regional wall motion.     

A clinical feature of myocardial stunning associated with acute myocardial infarction

We report a case of myocardial stunning after acute myocardial infarction. In the hyperacute phase of myocardial infarction, the patient’s coronary arteries showed normal features on coronary angiography during extensive ST-segment elevation observed on a standard 12-lead electrocardiogram and extensive akinesis observed on a left ventriculogram. Thallium-201 emission computed tomography revealed extensive perfusion abnormality. In the chronic phase, the perfusion abnormality was markedly improved. However, the electrocardiogram demonstrated poor R wave progression, and the left ventriculography revealed slight hypokinesis in the anterolateral wall. The acetylcholine provocation test disclosed coronary vasospasm of the left anterior descending coronary artery. About six months thereafter, left ventricular wall motion became completely normal and no poor R wave progression was observed on the electrocardiogram. The findings in this case indicate that myocardial stunning resulted from brief but severe ischemia due to vasospasm which led to cardiogenic shock, and that the recovery of findings for thallium-201 perfusion might be followed by those of electrocardiography and left ventriculography in the stunned myocardium.     

Identification of asynergic but viable myocardium in patients with chronic coronary artery disease by gated blood pool scintigraphy during isosorbide dinitrate and low-dose dobutamine infusion: Comparison with thallium-201 scintigraphy with reinjection

To evaluate the ability of low-dose dobutamine and isosorbite dinitrate (ISDN) gated blood pool scintigraphy (GBPS) and thallium SPECT with reinjection to identify viability in asynergic myocardium, both procedures were performed in 38 consecutive patients with chronic coronary artery disease and left ventricular dysfunction. Twenty-two of the 38 patients with successful revascularization were analyzed. GBPS was performed at the baseline and during continuous infusion of low dose dobutamine (5 μg/kg/min) and ISDN (2 μg/kg/min). Cine mode GBPS wall motion was scored from normal (0) to dyskinesis (4) semiquantitatively. Forty-seven of 110 segments with severe asynergy at the baseline were analyzed. Viability determined by GBPS was defined as wall motion score improvement by more than 1 grade. Thallium viability was defined as the segment with redistribution or fill in with severe initial perfusion defect. GBPS was 76.7% sensitive and 70.6% specific for predicting post vascularization wall motion improvement (p < 0.005). Of 47 segments with severe asynergy, concordance of judgement was obtained in 40 segments (85.1 %), and reversibility was correctly diagnosed in 34 of 40 patients (85.0%), but thallium with reinjection correctly identified tissue viability in 6 of 7 segments with discordance between 2 studies. These data suggest that most cases of reversible asynergy (hibernating myocardium) respond to ISDN and dobutamine, suggesting the possibility of predicting improvement by revascularization, although some underestimation of tissue viability remained to be resolved. Thallium with reinjection is superior to low-dose dobutamine + ISDN GBPS for the assessment of myocardial viability.     

Comparison of anatomical standardization methods regarding the sensorimotor foci localization and between-subject variation in H2 15O PET activation,a three-center collaboration study

Identical sets of H₂ ¹⁵O-PET brain activation data regarding vibrotactile stimulation and voluntary motion of the fingers in seven young normal subjects, together with the MRI, were analyzed in three PET centers by means of each center’s own method of anatomical standardization to Talairach’s frame. Every center used a linear or segmentally linear transformation with various number of scaling factors. A variation of 6–8 mm in each axis was observed in the foci localization due to the difference in the transformation principle and the measured brain size. Between-subject variation was similar in all the centers. Since different standardization methods define different coordinate systems, a cautious attitude should be taken to comparing results analyzed at different centers.     

Myocardial technetium 99m-labeled sestamibi single-photon emission computed tomographic imaging in the detection of coronary artery disease: Comparison between early (15 minutes) and delayed (60 minutes) imaging

Background

Previous studies have demonstrated that there is a “partial” myocardial redistribution of^99mTc-labeled sestamibi (MIBI) between 1 and 3 hours after intravenous injection at stress. The purpose of this prospective study was to compare MIBI single-photon emission computed tomographic (SPECT) imaging performed 15 and 60 minutes after the injection at stress in the detection of coronary artery disease.

Methods and results

Thirty-five patients with coronary artery disease (26 underwent coronary angiography and 23 had a positive²⁰¹Tl study result) were included in this study. SPECT imaging started 15 minutes after the injection of 25 to 30 mCi MIBI at peak stress (180-degree arc, 32 angles, 25 sec/view, and high-resolution collimator). Patients underwent reimaging at 60 minutes according to the same protocol and with the same gamma camera. A rest study was obtained 75 minutes after the injection of MIBI (25 to 30 mCi) at rest, 48 hours later. Images (divided for a total of 19 segments per patient) were interpreted by two blinded observers for patient diagnosis and segmental comparison. The patient diagnosis was the same for the two protocols: normal = 3, ischemia = 27, and scar = 5. The segmental agreement (k = 0.90) was 632/665 (95.0%). The imaging performed at 15 minutes detected normal, ischemia, and scar in 413, 189, and 63 segments, respectively, whereas the imaging performed at 60 minutes detected 422, 180, and 63 segments, respectively (difference not significant). The early and delayed images were placed side by side for subjective comparison of the extent of the defect. Early imaging showed slightly larger defects in six patients, equal defects in 24 patients, and slightly smaller defects in five patients. Ischemic/normal wall ratios were 0.67 ±0.16 at 15 minutes and 0.68 ±0.15 at 60 minutes.

Conclusions

There is no clinically significant difference between SPECT imaging performed at 15 minutes or 60 minutes after the injection of MIBI at stress. Furthermore, this study showed that it is feasible to obtain good-quality MIBI images even 15 minutes after the injection at stress.     

Total body and regional bone mineral content in hemodialysis patients

Bone mineral content (BMC) in the total body and lumbar spine was evaluated in 126 hemodialysis patients (60 males, 66 females) by dual photon absorptiometry with the Norland DBD 2600. Measurements of: 1) total body BMC divided by lean body mass (BMC_TB/LBM), 2) bone mineral density (BMD) of total body, 3) BMD of four regional sections (head, trunk, pelvis, and legs), and 4) BMD of lumbar spine, generally showed a significant decrease in the hemodialysis patients compared to the reference population. However, arm BMD did not show a significant difference between patients and control populations. The z-score of BMC_TB/LBM declined significantly throughout the duration of hemodialysis, although that of the lumbar spine BMD did not. It should be noted that the degree of decrease in BMC was more prominent in the total body measurement than in the lumbar spine measurement. There was preferential osteopenia of the total body in the hemodialysis patients. Although the lumbar spine BMD showed a lower value than the control population, the lumbar spine is not the recommended region to monitor the BMD change in hemodialysis patients.     

11C-labeled 2′-iododiazepam for PET studies of benzodiazepine receptors: Synthesis and comparison of biodistribution with its radioiodinated compound

For PET studies of benzodiazepine receptors, N-¹¹C-methyl-2′-iododiazepam (2′-IDZ) was synthesized by N-methylation of its desmethyl derivative with¹¹C-methyl iodide, and was subsequently purified by HPLC. The labeling and purification procedures were completed within 45 min after¹¹C-methyl iodide trapping, and the radiochemical yield (corrected for decay) was approximately 40% based on the initial trapped radioactivity of¹¹C-methyl iodide. Biodistribution studies in mice demonstrated that¹¹C-2′-IDZ was rapidly and noticeably accumulated in the brain, and subsequently decreased with time. Accumulation was greater in the cortex than in other brain regions. When compared with¹²⁵I-2′-IDZ, the distribution was almost the same until 5 min after injection, but levels were low after 20 min. Metabolic studies indicated that the difference between these two compounds in the time course of brain radioactivity distribution may be due to N-demethylationin vivo.