Aromatic L-amino acid decarboxylase turnover in vivo in rhesus macaque striatum: a microPET study.

The aromatic L-amino acid decarboxylase (AAAD) is involved in the de novo synthesis of dopamine, a neurotransmitter crucial in cognitive, neurobehavioral and motor functions. The goal of this study was to assess the in vivo turnover rate of AAAD enzyme protein in the rhesus macaque striatum by monitoring, using microPET imaging with the tracer [(18)F]fluoro-m-tyrosine (FMT), the recovery of enzyme activity after suicide inhibition. Results showed the AAAD turnover half-life to be about 86 h while total recovery was estimated to be 16 days after complete inhibition. Despite this relatively slow AAAD recovery, the animals displayed normal movement and behavior within 24 h. Based on the PET results, at 24 h, the animals have recovered about 20% of normal AAAD function. These findings show that normal movement and behavior do not depend on complete recovery of AAAD function but likely on pre-synaptic and post-synaptic compensatory mechanisms.

Aromatic L-amino acid decarboxylase (AAAD) inhibitors as carcinoid tumor-imaging agents: synthesis of 18F-labeled alpha-fluoromethyl-6-fluoro-m-tyrosine (FM-6-FmT).

The aromatic L-amino acid decarboxylase (AAAD) enzyme is significantly upregulated in neuroendocrine tumors and, thus, would be a good target for PET imaging agents. Alpha-fluoromethyl-DOPA (FMDOPA) is one of the most potent irreversible AAAD inhibitor and its non-catechol derivative, alpha-fluoromethyl-m-tyrosine (FMmT), is a promising AAAD imaging agent. We synthesized FMmT and its direct electrophilic fluorination provided a mixture of products identified by NMR analysis after HPLC purification as 6-fluoro-, 2-fluoro- and 2,6-difluoro-derivatives of FMmT. Using rat striatal homogenates, alpha-fluoromethyl-6-fluoro-m-tyrosine (FM-6-FmT) was found to have AAAD inhibitory activity comparable to that of FMDOPA. Electrophilic radiofluorination of FMmT using [18F]AcOF gave 18F labeled 6-fluoro-, 2-fluoro- and 2,6-difluoro-FMmT derivatives in 22.0%, 21.9% and 8.5% radiochemical yields, respectively. Based on its proposed mechanism of inhibition, FM-6-[18F]FmT is expected to irreversibly bind to AAAD and, hence, could be used as a PET agent to image tumors of endocrine origin containing high concentrations of AAAD. Since FM-6-FmT lacks the catechol moiety, it is expected to be better than FMDOPA since it is not a substrate for catechol-O-methyltransferase.

[Evaluation of technetium-99m-MIBI scintigraphy in metastatic differentiated thyroid cancer--comparison study with 131I and 201Tl].

Detectability of metastasis in differentiated thyroid cancer using technetium-99m-methoxyisobutyl isonitrile (99mTc-MIBI) was compared with that of 131I and 201Tl. Forty patients after total thyroidectomy were evaluated. The scan results were compared with those of 131I and 201Tl whole body scintigraphy per patient. The positive rate was 68% in 99mTc-MIBI, 84% in 131I, 60% in 201Tl respectively. As to the lymph node metastasis, the positive rates were 56% in 99mTc-MIBI, 78% in 131I, 39% in 201Tl. In lung metastasis, the positive rate was 46% in 99mTc-MIBI, 82% in 131I and 55% in 201Tl. Serum thyroglobulin (Tg) was significantly higher in 201Tl and/or 99mTc-MIBI positive group compared to that of negative group independent of 131I scan results. Although the detectability of both 99mTc-MIBI and 201Tl were inferior to that of 131I, 9 to 22% of metastasis were detected only by these radiopharmaceuticals. Both 99mTc-MIBI and 201Tl, therefore, should be used in cases with high serum Tg even with negative 131I uptake. Basing on the fact there was no prominent difference between 99mTc-MIBI and 201Tl in the detectability of metastasis, 99mTc-MIBI might be more suitable tracer because of better quality image.

A new radiopharmaceutical for the cerebral dopaminergic presynaptic function: 6-radioiodinated L-meta-tyrosine.

Geometric isomers of radioiodinated L-meta-tyrosine, 6-[I-125]iodo-and 4-[1-125]iodo-L-meta-tyrosine (6-I-L-mTyr, 4-I-L-mTyr) were separated by high-performance liquid chromatography . Both 6-I- and 4-I-L-mTyr had high energy-dependent brain accumulation. 6-I- and 4-I-L-mTyr were also metabolically stable and were rapidly excreted through the urine. 6-I-L-mTyr had a predilection for the cerebral aromatic L-amino acid decarboxylase (DOPA decarboxylase), the final enzyme of dopamine biosynthesis. 6-Radioiodinated L-mTyr is a new radiopharmaceutical that can be both useful in assessing cerebral amino acid transport mechanism and quantifying metabolically active DOPA decarboxylase.

rCBF in neurodegenerative diseases as estimated by the autoradiographic (ARG) method and delayed I-123-IMP studies.

A total of 24 patients with a mean age of 45.8 +/- 20.8 were included in the study. The patients were grouped as Control (C), Degenerative Syndromes (DS), Degeneration Associated with External Factors (DEF), Degeneration Associated with Focal Neurologic Lesion (DFN) and Demyelinating Disease (DM). Imaging started 15 minutes for early and 4 hours for delayed scans after i.v. infusion of I-123 IMP. The rCBF was calculated by the IMP autoradiographic (ARG) method. The wash-out ratio (WR) was calculated as the ratio of the Delay/Early count. In the rCBF of the various areas of the brain, significant differences were noted between various disease groups. No correlation was noted between rCBF and WR (r = -0.50). The WR of patients grouped according to various disease processes did not show a significant difference between various areas of the brain. In conclusion, the rCBF was effective in separating both various areas of the brain and disease entities. WR from a delayed study is less useful in neurodegenerative diseases.

Retention of Tc-99m ECD in delayed SPECT of the brain.

We determined the effect of retention on the changes in regional biodistribution of Tc-99m ECD in the brain. A total of 14 cases, 7 normal volunteers and 7 patients with various diagnoses but with very minimal radiologic findings or none were included in the study. SPECT images were taken at 30 min, 1, 2, 3, 4 and 6 hrs after an intravenous injection. Retention rates were calculated in various regions and were corrected according to the time decay of technetium. There was a tendency for the retention rate to increase up to three hours of imaging and then a decrease was noted in most regions of the brain. In the thalamus, increasing retention was noted. In conclusion, Tc-99m ECD retention in the different regions of the brain varies with time. These differences should always be considered when planning and interpreting SPECT quantitative studies.

Brain uptake of iodinated L-meta-tyrosine, a metabolically stable amino acid derivative.

The possibility of using L-meta-tyrosine (L-mTyr) with high metabolic stability and amino acid transport affinity was evaluated. mTyr was first separated into D- and L-isomers with high-performance liquid chromatography and both were labelled with non-carrier-mediated 125I. Biodistribution and pharmacological studies of radioiodinated mTyr in mice and rats were then performed. 125I-L-mTyr showed greater accumulation in the brain and the pancreas. It accumulated in the brain stereospecifically in the in vivo studies and by the L-tyrosine competitive energy dependent transport system in the in vitro studies. It was resistant to deiodination, appeared to have no retention mechanism and was rapidly excreted. 123I-L-mTyr has the potential of an amino acid transport marker, especially in the brain and the pancreas.

Further evolution of a literature database: the international use of a common software structure and methodology for the establishment of national consultation/liaison databases.

Every day there are 6000-7000 papers published in science. Since the C-L psychiatrist may be asked to consult on a patient with any medical illness, and who may be on any medical drug, methods need to be developed to review the recent literature and have an awareness of current findings. At the same time, teachers need to develop a current listing of seminal papers for trainees and practitioners of this subspecialty of psychiatry. Experts chosen because of their writings and acknowledged contributions to their subspecialty interests have sifted through thousands of articles to select the ones they regard as the most important for trainees in C-L psychiatry. In addition, certain countries--Spain, Portugal, Germany, Mexico, Australia and Brazil are developing national databases of C-L literature not only for their own use, but also to bring them to the attention of other parts of the world. This fifth iteration of the C-L literature database has especially targeted the period of 1996-1999--the millennium issue--in order to have easier access to contemporary essential studies on common problems. Part II of this issue describes the seminal cardiac drug-psychotropic drug interactions that the C-L psychiatrist may encounter in the most common medical disease in the United States--coronary heart disease--with advise to the practitioner as to their management. The use of the Internet and institutional Intranets is described.

Relationship between extraosseous accumulation in bone scintigraphy with 99Tcm-HMDP and histopathology.

We assessed the relationship between 99Tcm-HMDP extraosseous accumulation (EOA), the histopathology of primary lesions and various laboratory findings. In 155 of 4824 patients, 163 EOA were noted. Of these, 33.7% were in the abdomen, 27.6% in the chest, 22.7% in the extremities, 9.8% in the pelvic area and 6.1% in the head and neck area. We found that 72.4% of EOA were due to malignant processes and 27.6% to benign processes. In the abdomen, 36.6% of the EOA were due to hepatocellular carcinoma and intestinal carcinoma. In the chest, 46.7% of EOA were a result of breast carcinoma. In the extremities, 28.7% of the EOA were due to sarcoma. The mean white blood cell count was elevated (8.0 +/- 6.3 x 10(3)) in patients with malignant processes. The mean serum haemoglobin and haematocrit in benign and malignant processes, for both males and females, were below normal values. All other laboratory findings were within normal limits. Significant differences in serum haemoglobin and haematocrit were noted between male and female patients with benign processes (P = 0.04 and P = 0.04, respectively). No other significant differences between benign and malignant processes were noted. Therefore, EOA is more frequently associated with malignant processes of primary lesions and is often accompanied by leukocytosis and anaemia.

Gallium-67 scintigraphy in the treatment and prognosis of acute adult T-cell lymphoma.

The case of a 77-year-old male patient who complained of left upper quadrant pain and progressive vomiting. Laboratory examination showed extremely high lactic acid dehydrogenase (LDH) and adult T-cell leukemia antibody (ATLA). The anatomical studies CT, MRI, US and upper GI series substantiated an omental lymphadenopathy which was causing a circumferential compression of portions of the duodenum and jejunum. Gallium-67 citrate (Ga-67) scintigraphy showed high uptake at LUQ. Ultrasound guided biopsy failed to confirm the diagnosis. Irradiation was performed. Ga-67 scintigraphy had a contributory role in clinical subtyping of the disease, planning of treatment, posttreatment assessment and prognostication of adult T-cell lymphoma.

[Evaluation of brain tumor by 99mTc-MIBI: comparison study with 201Tl and predictivity of therapeutic effect].

We compared the detectability of 99mTc-MIBI and 201Tl-chloride for brain tumor in relationship with histopathology. We also evaluated correlation between therapeutic effect using ACNU, Cisplatine and the degree of MIBI tumor uptake. The subjects were 31 brain tumor histologically confirmed by operation or biopsy. Dual-isotope SPECT technique was performed at both 20 min and 180 min after tracer injection. A tumor to normal lung ratio on both early (ER) and delayed image (DR) and retention index (RI) were calculated. The positive rates of 99mTc-MIBI (90.3% and 77.4%) were comparable to that of 201Tl (90.3% and 80.6%). In the relationship with histopathology, both MIBI and Tl accumulated in 100% of glioblastoma (GBM), metastasis (meta), anaplastic astrocytoma and 25% of low grade astrocytoma on both early and delayed images. On semiquantitative analysis, there were no statistical significance among GBM, meta and anaplastic astrocytoma of ER, DR, RI in the both radiopharmaceuticals. However, both ER and DR in GBM tended to be higher than those of anaplastic astrocytoma. In spite of intense MIBI uptake, GBM patients died within six months except one patient. We concluded that MIBI can be helpful in detecting brain tumor as Tl. MIBI also might be useful in estimating the degree of malignancy in glioma. However, intense MIBI uptake did not mean favorable therapeutic effect in patients with GBM treated with ACNU and Cisplatine.

123I-MIBG myocardial scintigraphy in diabetic patients: relationship with 201Tl uptake and cardiac autonomic function.

PURPOSE: To investigate the influence of diabetic myocardial damage (suspected myocardial damage; SMD) diagnosed by 201Tl-SPECT and diabetic cardiac autonomic neuropathy (AN) on myocardial MIBG uptake in patients with non-insulin-dependent diabetes mellitus (NIDDM). SUBJECTS AND METHODS: Eighty-seven diabetic patients divided into four subgroups: 23 with SMD (+) AN (+); 19 with SMD (+) AN (-); 27 with SMD (-) AN (+); 18 with SMD (-) AN (-), and 10 controls were studied. Both planar and SPECT images were taken at 30 minutes (early) and 3 hours (delayed) after 123I-MIBG injection. The heart to mediastinum uptake ratio (H/M) and washout ratio of 123I-MIBG (WR) were obtained from both planar images. On SPECT images, the total uptake score (TUS) was obtained by the 5 point score method by dividing the myocardium into 20 segments on visual analysis. Similarly, the difference between the 201Tl image and the 123I-MIBG image in TUS was taken as the difference in the total uptake score (delta TUS) representing cardiac sympathetic denervation without SMD. RESULTS: On both early and delayed planar images, the mean H/M value in the subgroups of diabetic patients was significantly lower in the SMD (+) AN (+) group than in the control group, but among those subgroups, there was statistically significant difference between the SMD (+) AN (+) and SMD (-) AN (-) groups only on the delayed images. Regarding the WR value, there was no statistically significant difference among subjects. On SPECT image analysis, the diabetic subgroup with AN or SMD had statistically significant lower values for TUS than those of the control group. Among diabetics, there was a statistically significant differences between SMD [+] AN [+] and SMD [-] AN [-] on both early and delayed images. Similarly, the SMD [+] AN [-] group also had significantly lower values than those of SMD [-] AN [-] on early images. Regarding delta TUS, there was a statistically significant differences between AN [+] subgroups and controls. Similarly, the mean value for delta TUS was much higher in AN [+] subgroups than in AN [-] subgroups with or without SMD in diabetes mellitus. CONCLUSION: 123I-MIBG myocardial uptake is affected by both SMD and cardiac autonomic neuropathy. Based on the finding that delta TUS was much higher in AN [+] subgroups and there was no statistically significant difference between SMD [+] AN [+] and SMD [-] AN [+] subgroups, a decrease in myocardial 123I-MIBG uptake might progress independently of SMD.

[123I-MIBG lung uptake in patients with diabetes mellitus].

The purpose of this study is to clarify the relationship between 123I-MIBG lung uptake and silent myocardial ischemia (SMI), cardiac autonomic neuropathy (AN) or clinical characteristics. For the quantitative analysis, lung to upper mediastinum uptake ratio (L/M) and heart to upper mediastinum uptake ratio (H/M) were obtained from chest planar image. In addition, both lung washout ratio (%WR-L) and heart washout ratio (%WR-H) were calculated from early and delayed images. Each indices were compared in both diabetic and control groups. Mean values of H/M in diabetes with complication were significantly lower than those of control group. Particularly, AN(+)SMI(+) group showed lowest value. Similarly, mean values of %WR-H in diabetes with complication were significantly higher than those of control group and AN(+)SMI(+) group showed highest value. Although mean value of L/M in each diabetic group was significantly higher than that of control group, there was no statistical significance among each diabetes except AN(+)SMI(-) group on early image. Mean value of %WR-L in AN(+) or SMI(+) group was also significantly higher than that of control group, but there was no statistical significance among each diabetic group. The current study suggested that high pulmonary 123I-MIBG uptake in diabetes was independent of the complication of SMI or AN. Pulmonary endothelial dysfunction related with severity of diabetes mellitus was considered to be the most important factor.

[Evaluation of primary lung cancer and mediastinal lymph node metastasis using 99mTc-MIBI: comparison with 201T1 and relation to chemotherapeutic effect].

We compared the detectability of 99mTc-MIBI and 201T1-chloride for primary lung cancer and mediastinal lymph node metastasis. We also analyzed the relationship between 99mTc-MIBI uptake and effectiveness of chemotherapy in patients with small cell lung cancer. The subjects were fourty-six primary lesions and 8 mediastinal metastatic lymph nodes confirmed by operation, and dual-isotope SPECT technique was performed at both 20 min and 180 min after tracer injection. A tumor to normal lung ratio on both early (ER) and delayed image (DR) and retention index (RI) were calculated. The positive rates of 99mTc-MIBI (early; 82.6%, delayed; 54.3%) were comparable to 201T1 in most primary tumor (87.0% and 84.8%). Whereas tumor smaller than 3 cm diameter was poorly visualized on both 99mTc-MIBI (25% and 0%) and 201T1 (37.5% and 37.5%). Detectabilities of metastatic mediastinal lymph nodes of 99mTc-MIBI (62.5% and 25.0%) was comparable to those of 201T1 (62.5% and 50.0%). Regarding effectiveness of chemotherapy, NC group showed lower uptake of 99mTc-MIBI and significant lower value of RI compared to PR group. We concluded that early image of 99mTc-MIBI SPECT can be helpful in detecting primary lung cancer and metastatic mediastinal lymph node. Additionary, it might be useful for predicting the effects of chemotherapy in small cell lung cancer.

Gadolinium-enhanced MR imaging of thyroid and parathyroid masses.

PURPOSE: To evaluate spin-echo and contrast material-enhanced dynamic magnetic resonance (MR) imaging in characterization of thyroid and parathyroid masses. MATERIALS AND METHODS: Conventional T1- and T2-weighted, gadolinium-enhanced dynamic, and gadolinium-enhanced T1-weighted spin-echo imaging sequences were performed in 85 patients with thyroid and parathyroid tumors. Findings from spin-echo imaging and dynamic curve patterns from mean signal intensity ratios were evaluated for each histologic tumor type. RESULTS: T1- and T2-weighted imaging did not enable differentiation of benign from malignant tumors. Primary thyroid lymphoma enhanced less than other solid thyroid tumors, and parathyroid adenoma also enhanced less than other tumors (P < .05 compared with papillary carcinoma. CONCLUSION: Gadolinium-enhanced MR imaging cannot enable prediction of histologic type in thyroid and parathyroid tumors. However, in cases of multiple tumors, the technique may improve the contrast between the different histologic types and sometimes suggest the diagnosis of primary thyroid lymphoma or parathyroid adenoma.

[Usefulness of rCBF SPECT in patients with encephalitis: comparison study with MRI].

Twenty-nine rCBF SPECT study was done in 17 patients with encephalitis. Five of 6 patients (83.3%) showed regional high uptake in acute phase within a week after onset and 16 of 23 studies (69.6%) showed regional low uptake in subacute and chronic phase. Six of 19 lesions (31.6%) with regional high uptake changed to low uptake and 11 lesions (57.9%) improved to normal uptake on follow up studies. Seventeen of 51 lesions with low uptake (33.3%) improved to normal uptake. On the comparative study with MRI, 8 of 18 (44.4%) high uptake area showed cortical thickness or high intensity on T2 weighted images. Thirty-six of 74 low uptake area (48.6%) showed cortical thickness, brain atrophy or high intensity on T2 weighted images. Forty-eight of 212 regions (22.6%) with normal MRI findings showed abnormal accumulation of cerebral tracer on rCBF SPECT studies. rCBF SPECT was useful tool for diagnosis and follow up management in patients with encephalitis.

[A case of transient tic disorder with abnormal findings on 99mTc-HMPAO SPECT].

We report a case of transient tic disorder with abnormal findings on 99mTc-HMPAO SPECT. The patient was 5-year-old girl with vocal and motor tic. There was no evidence of structural abnormality on magnetic resonance imaging (MRI). Electroencephalogram (EEG) showed spikes and sharp waves on both frontal lobes and parietal lobes (left-side dominant). 99mTc-HMPAO SPECT demonstrated focal regions of hyperperfusion in the both frontal lobes, both parietal lobes and right temporal lobe corresponding to the abnormal findings detected by EEG. It also demonstrated an area of hyperperfusion in the right basal ganglia. It is suggested that 99mTc-HMPAO SPECT is useful for the diagnosis and the understanding of the clinical state of tic disorder.

The use of 201Tl SPET to predict the response to radiotherapy in patients with head and neck cancer.

Thallium-201 (201Tl) is widely used in the diagnosis of malignant tumours. However, its use in predicting the response to radiation therapy for head and neck cancer has not been established. Nineteen patients with histologically proven head and neck cancer were studied. 201Tl single photon emission tomographic (SPET) images were obtained 15 min (early) and 4 h (delayed) post-injection of the radionuclide. For a semi-quantitative assessment, regions of interest were drawn over the lesions and normal soft tissue. Lesion-to-normal tissue uptake ratios of 201Tl activity were measured from mean counts-per-voxel obtained on both the early and delayed scans, representing the early index (EI) and delayed index (DI) respectively. Subsequently, a retention index (RI) was calculated using the formula: RI = (DI - EI) x 100/(EI). The patients were classified into two groups according to the effect of radiotherapy: a partial response or complete response group (PR-CR group) and a no change group (NC group). In the analysis of primary lesions, both the delayed and retention indexes of the PR-CR group were significantly higher than those of the NC group. However, the early index was not significantly different between the two groups. In the metastatic lymph nodes, only the retention index was significantly different between the two groups. Our results demonstrate that 201Tl SPET and a 201Tl index can be used to predict the response to radiotherapy for primary head and neck cancer and lymph node metastases. The retention index is a useful parameter for estimating the effects of radiotherapy.

Increased bone marrow uptake of Ga-67 in patients with fever of unknown origin.

The relationships of clinical diagnosis, the effect of blood chemistry, and the clinical implication of increased Ga-67 citrate uptake in the bone marrow of patients with signs and symptoms of fever of unknown origin were studied. Based on intensity of Ga-67 citrate uptake in bone marrow, patients were classified as follows: type 1 when there was no evidence or very faint bone marrow uptake in the vertebrae, type 2 when mild to moderate, type 3 when uptake was severe. The relationships of WBC count, hemoglobin, hematocrit, serum iron, and unsaturated iron-binding capacity with the occurrence of increased bone marrow uptake in the different groups were noted. Analysis of variance with Fisher's protected least significant difference was used. A P value of less than 0.05 was considered significant. The results showed significant differences between types 1 and 2 and between types 1 and 3 for WBC counts, hemoglobin, and hematocrit levels. Serum iron concentration and unsaturated iron-binding capacity, however, did not show any significant differences. Significant changes in WBC count, hemoglobin and hematocrit in patients with fever of unknown origin were accompanied by a varying intensity of Ga-67 citrate uptake in the bone marrow.