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Background: Various styrylbenzene compounds were synthesized and evaluated as mainly Aβ amyloid sensors. These compounds, however, cannot be used for detecting amyloid deposition in peripheral nerves because of the inherent sensitivity of the compounds. These compounds often generate false positives especially in the basement membrane of blood vessels in histochemical studies. To overcome these problems, we must first synthesize other styryl compounds for detecting amyloid fibrils in tissues., Methods: A wide variety of symmetrical and unsymmetrical styrylbenzene derivatives were synthesized and then these compounds were used to detect amyloid fibrils in autopsy and biopsy samples from patients with various systemic and localized forms of amyloidosis such as familial amyloidotic polyneuropathy (FAP), senile systemic amyloidosis (SSA), amyloid A (AA) amyloidosis, localized AL amyloidosis, and Alzheimer's disease., Results: 1-Methoxy-2,5-bis-styrylbenzene and 2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-2,5-bis-styrylbenzene (EEEFSB) detected amyloid fibrils in both in vitro and in vivo histopathological studies. 1-Methoxy-2,5-bis-styrylbenzene also showed a high strength of fluorescence with amyloid deposition in peripheral nerves in a patient with FAP., Conclusions: 1-Methoxy-2,5-bis-styrylbenzene and EEEFSB may prove a useful tool for diagnosing amyloidosis, not only in a histochemical study but also in whole body amyloid positron emission tomography (PET) imaging., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: To determine the usefulness of positron emission tomography (PET) with (11)C-acetate (AC) for imaging lung adenocarcinoma and evaluating its tumor aggressiveness, AC- and (18)F-fluorodeoxyglucose (FDG)-PET were compared., Methods: One hundred and sixty-nine adenocarcinomas with clinical stage IA and 53 benign nodules were examined by both AC- and FDG-PET before surgery. The sensitivity and specificity for discriminating benign/adenocarcinoma were compared between AC- and FDG-PET. The AC and FDG uptakes were examined to determine the relationship with tumor aggressiveness, i.e., pathological tumor stage, lymphatic, vascular, or pleural involvement, and proliferative activity determined by Ki-67 staining score., Results: While the sensitivity of AC-PET was significantly higher than FDG-PET for bronchioloalveolar carcinoma (BAC) and well-differentiated (W/D) adenocarcinoma (p < 0.001 and 0.006, respectively), there was no significant difference for moderately or poorly differentiated adenocarcinoma. The specificity was not different between them. While FDG uptakes were significantly higher in tumors with pathological advanced stages or those with lymphatic, vascular and/or pleural involvements than in tumors with pathological stage IA or those without these tumor involvements (p = 0.04 to p < 0.001), AC uptake did not show significant differences between the respective sub-groups except according to the tumor stage. While both AC and FDG uptakes showed a significant correlation with Ki-67 staining scores (p = 0.03 and p < 0.001, respectively), the correlation coefficient of former was lower than that of latter (p = 0.07)., Conclusions: While AC-PET can image BAC and W/D adenocarcinoma with a higher sensitivity than FDG-PET, it cannot evaluate tumor aggressiveness of clinical stage IA lung adenocarcinoma as well as FDG-PET.

Background: The objective of this study was to clarify the usefulness of positron emission tomography (PET) using(18)F-fluorodeoxyglucose (FDG) and carbon 11-labeled acetate (AC) for predicting the histologic types and tumor invasiveness of thymoma in a multicenter study., Methods: Forty thymomas were examined using both FDG-PET and AC-PET before surgery. The histologic types were type A in 1 thymoma, type AB in 12 thymomas, type B1 in 11 thymomas, type B2 in 7 thymomas, type B3 in 6 thymomas, and type C in 3 thymomas. Tumor invasiveness was assessed by pathologic tumor stage and was identified as stage I in 17 tumors, stage II in 17 tumors, stage III in 4 tumors, and stage IV in 2 tumors. FDG and AC uptake was measured as the maximum standard uptake value (SUV)., Results: The FDG-SUV in type C thymomas was significantly higher than that in the other types (A-B3; P = .001 - P = .048). The AC-SUV in type A/AB thymomas was significantly higher than that in the other tumor types (B1-C; P < .001 - P = .002). All 3 type C tumors had an FDG-SUV >or=6.3, and all 13 type A/AB tumors had an FDG-SUV <6.3 and an AC-SUV >or=5.7. All 17 thymomas that had an FDG-SUV <6.3 and an AC-SUV <5.7 were type B1, B2, or B3. Neither the FDG-SUV nor the AC-SUV differed significantly between the stages I/II tumors and stage III/IV tumors., Conclusions: Although neither the FDG-SUV nor the AC-SUV can predict the invasiveness of thymomas assessed by tumor stage, they are useful for predicting histologic types of thymoma. Thymomas with an FDG-SUV <6.3 and an AC-SUV >or=5.7 almost certainly are types A/AB, which is of considerable prognostic and management significance., ((c) 2009 American Cancer Society.)

A 45-year-old female was referred to our hospital due to right anterior chest pain. A chest X-ray and a computed tomographic examination showed a large cystic lesion in the right pleural cavity above the diaphragm. The internal surface of the cyst seemed to be smooth and the content was homogeneous suggesting clear liquid. Under the diagnosis of the benign pericardial cyst, a thoracoscopic surgery was performed using a double-balloon catheter. Aspiration of the cyst content by the double-balloon catheter minimized the spillage of the content into the thoracic cavity. Furthermore, the double-balloon catheter allowed the cyst wall to be more easily grasped and manipulated. We confirmed the usefulness of a double-balloon catheter for the thoracoscopic resection of giant cystic lesions.

In the current study, to elucidate the clinical features of severe malaria, we performed whole-body positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) of Plasmodium coatneyi-infected acute-phase Japanese macaques. The infected monkeys clearly exhibited increase in splenic FDG uptake indicating marked enhancement of glucose metabolism. The standardized uptake values (SUVs) of the spleen in the infected monkeys were significantly higher than those in the uninfected monkey. At autopsy, splenomegaly was clearly present in all infected monkeys, and histopathologic findings included hyperplasia of lymphoid follicles in white pulp, a large number of activated macrophage, and congestion of parasitized red blood cells (PRBCs) and malaria pigments in red pulp. We suggest that increase in splenic glucose uptake may thus be closely related to activation of splenic clearance system against blood-stage malarial parasites.

Cerebral metabolic changes in Japanese macaques (Macaca fuscata) infected with Plasmodium coatneyi, a primate model of severe human malaria with cerebral involvement, were directly evaluated by fluorodeoxyglucose-positron emission tomography (FDG-PET). We observed diffuse and heterogeneous reduction of metabolism in the cerebral cortex in the acute phase of malaria infection. Neuropathologic examination showed preferential sequestration of parasitized red blood cells in the cerebral microvasculature. However, hemorrhagic change or necrosis was not observed in hematoxylin and eosin-stained and Nissl-stained brain tissues. This suggests that reduction of cerebral metabolism occurs before parenchymal changes appear in the brain. This may be one reason why more than half of the patients with cerebral malaria have no neurologic sequelae after recovery.

Gliomatosis cerebri is a rare condition in which an infiltrative glial neoplasm spreads through the brain with preservation of the underlying structure. CT and MRI show diffuse abnormal density or signal, without mass effect, and because these findings are nonspecific, it is difficult to make a definitive diagnosis. Our purpose was to assess the usefulness of a new tumour-detecting amino acid tracer for positron-emission tomography (PET), L-[3-(18)F] alpha-methyl tyrosine (FMT), in patients with gliomatosis cerebri. We performed FMT PET, fluorodeoxyglucose FDG PET and MRI eight patients with gliomatosis cerebri and six with non-neoplastic disease, whose MRI also showed diffuse high signal on T2-weighted images. Standardised uptake (SUV) of FMT and FDG in the area of gliomatosis was obtained and the tumour-to-normal cortex (T/N) ratio of this was compared. The tumours were shown on FMT PET as areas of increased uptake, except in one patient with severe intracranial hypertension. There were significant differences between the SUV of FMT and the T/N ratio of FMT in patients and in controls (both P<0.01), and between the T/N ratio of FMT and FDG in patients ( P<0.01). Increased uptake of FMT PET strongly suggests neoplasia. FMT PET is valuable for differentiating gliomatosis cerebri from non-neoplastic diseases showing similar diffuse high signal on T2-weighted images and little contrast enhancement.

Purpose: Recently, a new positron emission tomography (PET) tracer, carbon-11 choline, has been introduced in oncology investigations, but the role of choline PET in musculoskeletal tumor evaluation has not been previously examined. This is the first trial to investigate the utility of choline PET in evaluating musculoskeletal tumors in comparison with fluorine-18 fluoro-2-deoxy-D-glucose (FDG) PET., Method: Thirty-three patients were examined with both choline PET and FDG PET, of which standardized uptake values (SUVs) were used for evaluation of the lesions. To decide the appropriate cutoff value and compare the two PET studies, receiver operating characteristic curve analysis was used. The binomial test was used for comparison of sensitivities between choline PET and FDG PET., Results: A significant correlation (r = 0.537, P = 0.0013) between choline and FDG SUVs was noted for all lesions (n = 33). Mean SUVs for malignant tumors were significantly higher than those for benign lesions in both choline PET and FDG PET. Using a cutoff value of 2.7 for choline SUVs, the sensitivity for correctly diagnosing malignancy was 92.3% (12/13) with a specificity of 90.0% (18/20), resulting in an accuracy rate of 90.9%. With use of a cutoff value of 3.3 for SUVs in FDG PET, the sensitivity was 84.6% (11/13) with a specificity of 80.0% (16/20), resulting in an accuracy rate of 81.8%. The receiver operating characteristic curves of two analyses showed that the mean area under the curve value of choline PET (0.9577 +/- 0.041) was significantly greater (P = 0.0488) than that of FDG PET (0.8192 +/- 0.0806). There was no significant difference in sensitivity and specificity between choline PET and FDG PET analysis using either the binomial test (P = 0.4531) or McNemar test (P = 0.371)., Conclusion: Choline PET analysis may not be inferior to FDG PET analysis for differentiating malignant from benign musculoskeletal tumors. The advantages of choline PET were shorter examination time and little retention in the bladder; therefore, this modality may be useful for preoperative planning for musculoskeletal tumors, especially for lesions around the hip joints.

We wanted to know whether airway remodeling caused by chronic exposures to antigen differed depending on the degree of maturation of animals. We sensitized guinea pigs at different stages of maturation: juvenile (approximately 200 g in body weight), adult (400 g), and old animals (800 g). Then, animals were repeatedly challenged with inhaled ovalbumin (0.3% or 3%) or vehicle twice a week for 6 wk. After the final challenge, the lungs were excised for the histologic evaluation of changes in the thickness of the inner wall area (Ti), the smooth muscle area (Tm), and the outer wall area (To) in noncartilaginous airway dimensions. To clarify whether or not the observed changes were due to renewal of airway cells, we stained the samples with labeled nucleotide 5'-bromo-2'-deoxyuridine (BrdU), which we injected repeatedly during the challenge periods. Chronic exposures to antigen induced airway wall thickening regardless of their stages of maturation. However, prominent areas of thickening differed between the three groups. Ti increased more remarkably in juvenile and adult animals than in old ones. By contrast, Tm significantly increased only in old animals. BrdU staining revealed more renewal of epithelial cells in juvenile and adult animals than in old ones (juvenile >or=adult > old), suggesting that increased renewal of epithelial cells contributed to the thickening of Ti in juvenile and adult animals. By contrast, only a slight increase in smooth muscle cell renewal was found even in old animals, indicating that an increase in Tm was due to factors such as hypertrophy. These results show that the development of antigen-induced airway remodeling is partly modified by the degree of maturation of animals in vivo.

The tumor-seeking agent most widely used in positron emission tomography (PET) is 2-(18)F-fluorodeoxy-D-glucose (FDG). The clinical usefulness of FDG PET has already been proved in detecting, staging and restaging various kinds of malignant tumors, but nuclear medicine physicians suffer from a "diagnostic dilemma," in which a relatively high false positive ratio of FDG PET in diagnosing malignant tumors prevails. To increase more specific tumor uptake or more specific tumor characterization, numerous PET radiopharmaceuticals have been developed, and some of them are being tested in clinical trials. This review will briefly survey the tumor uptake mechanism and clinical significance of representative non-FDG PET radiopharmaceuticals used in clinical trials for patients with cancers.

Purpose: To compare the diagnostic potential of whole-body positron emission tomography (PET) with fluorine 18 alpha-methyl tyrosine (FMT) with that of whole-body PET with 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG)., Materials and Methods: Nineteen patients with or suspected of having malignant tumors and five healthy volunteers underwent whole-body PET with FMT and FDG., Results: In comparison with FDG uptake, FMT uptake was significantly less in the brain, heart, lung, liver, and spine. On a lesion-by-lesion basis, the sensitivity of whole-body FMT PET for depicting malignant tumors was inferior to that of whole-body FDG PET, but this difference was not statistically significant (74% [26 of 35 lesions] vs 91% [32 of 35 lesions], P >.05). The positive predictive value of FMT PET was superior to that of FDG PET (87% [26 of 30 lesions] vs 63% [32 of 51 lesions], P <.001). The difference in uptake between benign and malignant lesions was significant with FMT PET (mean +/- SD, 1.64 +/- 0.96 vs 0.79 +/- 0.23; P <.001) but not with FDG PET (5.02 +/- 3.56 vs 4.02 +/- 2.90, P >.05)., Conclusion: Whole-body FMT PET is clinically useful in the diagnosis of malignant tumors and may be effective in the depiction of primary and metastatic lesions in the cardiac region or in the brain.

Positron emission tomography (PET) has become a very useful adjunct to anatomic imaging techniques, because it can provide an in vivo method for quantifying functional metabolism in normal and diseased tissues. Clinical trials with [(18)F] 2-deoxy-2-fluoro-D-glucose (FDG), the most commonly used radiolabeled tracer for PET imaging, has demonstrated increased accumulation of FDG in cancer tissue. FDG-PET is now widely used for the detection, differentiation, grading, staging, and monitoring of various neoplasms. However, the significance of FDG-PET in such evaluations of primary bone tumors and tumor-like lesions has not been extensively elucidated. In this article, we present recent advances in FDG-PET studies for evaluating primary bone tumors and tumor-like lesions.

Aim: A comparative study of the images obtained with a dual-head coincidence gamma camera with thick NaI crystals (19 mm), a dedicated PET camera with BGO crystals and a conventional gamma camera with thin NaI crystals (9.5 mm) was conducted to clarify the clinical feasibility of a dual-head coincidence gamma camera with thick NaI crystals., Methods: FDG images of 27 patients with malignant tumors were obtained by means of a dual-head coincidence gamma camera with thick NaI crystal and a dedicated PET camera with BGO crystals. The images of bone scintigraphy in 10 cancer patients obtained with the dual-head coincidence gamma camera were compared with those taken by a conventional dual-head gamma camera with thin NaI crystals., Results: Patient-basis sensitivity in 27 patients with neoplasms and lesion-basis sensitivity of the dual-head coincidence gamma camera and the dedicated PET camera were 74.1% and 85.2% (n.s.), 66.7% and 72.2% (n.s.), respectively. The tumor to background FDG uptake ratio derived from the coincidence gamma camera was significantly lower than that derived from the dedicated PET camera (mean +/- s.d.; 3.48 +/- 3.77 vs. 8.12 +/- 8.92, p < 0.0001), but the tumor to background FDG uptake ratio obtained with both methods correlated well (r = 0.84, p < 0.001). Similar whole body bone scans were obtained with the dual-head coincidence gamma camera and the conventional dual-head gamma camera in all 10 patients., Conclusion: These results suggest that the dual-head coincidence gamma camera with thick NaI crystals has potentially high clinical applicability for community hospitals.

Fluorine-18 labelled alpha-methyltyrosine (FMT) was developed for positron emission tomography (PET) imaging, and its potential for clinical application in patients with brain tumours has been demonstrated. This is the first trial to compare FMT with 18F-fluoro-2-deoxy-D-glucose (FDG) for the evaluation of musculoskeletal tumours. Seventy-five patients were examined with both FMT- and FDG-PET within a 2-week period. Imaging findings were visually inspected in conjunction with computed tomography and/or magnetic resonance imaging, and standardized uptake values (SUVs) for both FMT and FDG in lesions were also generated and compared with histological findings. A significant correlation between FMT and FDG SUVs was found for all lesions (r=0.769, P<0.0001), and mean values for malignant tumours were significantly higher than those for benign lesions in both FMT- and FDG-PET. The diagnostic sensitivities and specificities for malignancy were 72.7% and 84.9%, respectively, using FMT with a cut-off SUV of 1.2, and 72.7% and 66.0%, respectively, using FDG with a cut-off SUV of 1.9. The resultant accuracy with FMT was 81.3%, higher than that for FDG (68.0%), and the difference with respect to specificity was significant (chi2cal=5.0625, P<0.05). On the other hand, while a significant correlation was found between malignant tumour grade and SUV with both FMT- (rho=0.656) and FDG-PET (rho=0.815), only the latter demonstrated significant differences among grades I, II and III. FMT and FDG for PET appear equally effective at detecting musculoskeletal tumours. In evaluating musculoskeletal tumours, FMT may be superior to FDG in the differentiation between benign and malignant tumours, while FDG may be the better choice for non-invasive malignancy grading.

The present investigation was undertaken to identify the long-lived radionuclide and its chemical forms existing in [15O]water which was synthesized from 15O produced by the nuclear reaction 14N(d,n)15O, and to develop a method for its removal to facilitate radioactive waste disposal. The long-lived nuclide was identified as tritium based on a comparison of its physical half-life and the energy spectrum of beta-rays with those of tritium. The major chemical form of tritium in the target gas was estimated to be molecular hydrogen. The tritium radioactivity was completely removed without a serious loss occurring to the yield of [15O]water by passing the irradiated target gas over a heated palladium catalyst followed by a calcium chloride column before the final synthesis of the [15O]water. This provided a practical way of removing tritium from the [15O]water.

We assessed the accuracy of the standardized uptake value (SUV) measured by simultaneous emission and transmission scanning in cancer patients using FDG positron emission tomography (PET). Conventional, independent emission (E)/transmission (T) scans and simultaneous E/T scans were conducted consecutively in 30 patients who underwent FDG PET examinations. The SUVs of 35 mass lesions and 34 selected normal tissues were derived from the independent E/T scan and simultaneous E/T scan. Experimental studies using a cylindrical phantom were also conducted to evaluate the accuracy and reproducibility of the SUV derived from a simultaneous E/T scan. The SUVs of 18F solution in the phantom were estimated to be approximately 1, with high reproducibility in the range of total counts observed in the clinical examinations. There were no significant differences in the SUVs in 35 tumours derived from simultaneous E/T scans and those derived from independent scans, and there was a strong positive correlation between the two (r = 0.99, P < 0.01). There were also no significant differences in the SUVs in 34 normal tissue regions derived from simultaneous E/T scans and those derived from independent scans. In conclusion, simultaneous E/T scanning with FDG in patients with malignant tumours is a valid method, since the SUV derived from the simultaneous scan is accurate and reproducible.

Preliminary studies of 186Re-labelled 3-amino-1-hydroxypropylidene-1, 1-bisphosphonic acid (APD) were performed to determine its potential for bone pain palliation, and as a treatment for increased bone resorption. The synthesis of 186Re-APD was carried out by reduction of 186Re-perrhenate in the presence of SnCl2. The APD kit, comprising 2.5 mg of APD, 2.5 mg of gentisic acid and 1 mg of Sn++ as SnCl2 2H2O, was prepared in-house. The APD was labelled with 186Re and injected intravenously into normal mice. Mice were subsequently sacrificed at 1, 3, 24, 48, 72, 168 and 240 h post-injection. The greatest accumulation of 186Re-labelled APD was found in bone, resulting in bone-to-blood ratios of 25, 35, 65, 100, 151, 181 and 189, respectively. 186Re-APD showed high uptake in bone, and relatively low uptake in soft tissue, suggesting that 186Re-APD is a potential agent for bone therapy.

Brain and tumor uptake of [18F-alpha-methyl]tyrosine (18F-AMT) and the incorporation into each of four fractions (lipid, RNA, DNA and protein) were investigated in mice bearing LS180 colorectal carcinoma. Homogenized tissues were analyzed by the fractionation method into an acid-soluble fraction (ASF) and an acid-precipitable fraction (APF). The APF was further investigated to assess the incorporation of 18F-AMT into each fraction. Incorporation into four fractions of brain and tumor at 60 min post-injection was 20 and 12%, respectively; 10% of the activity was incorporated to lipid in brain and 5% in tumor. There was 5, 2 and 2% incorporation with RNA, DNA and protein, respectively. Metabolites in ASF were analyzed by high-performance liquid chromatography and thin-layer chromatography. There was only one radioactive peak, which corresponded to 18F-AMT. The incorporation of 18F-AMT into lipid was twice that of 18F-AMT in tumor. The uptake of 18F-AMT in tissues was rapid and accomplished before 30 min, and then slowly diffused in blood. These results implied that 18F-AMT was metabolized to protein to only a small extent and trapped as intact 18F-AMT in cells up to 60 min. We conclude that 18F-AMT is a promising tracer for tumor imaging and quantification of the transport rate using two-compartment models.

Unlabelled: We have developed 18F-labeled alpha-methyl tyrosine (FMT) for PET imaging. The aim of this study was to evaluate the clinical application potential of FMT for patients with brain tumors., Methods: Eleven healthy volunteers and 20 patients with brain tumors were injected with 185 MBq (5 mCi) FMT. In 3 healthy volunteers, whole-body imaging and urinary and plasma analysis were conducted for the assessment of the biodistribution of FMT. The normal range of cortical standardized uptake value (SUV) as a reference for comparing tumor SUV of FMT was estimated by using PET data obtained at 30 min postinjection in 8 healthy volunteers. Dynamic PET scans were conducted for 100 min in 4 healthy volunteers and for 30 min in 15 patients with brain tumors. The 10-min static images in another 4 volunteers and all patients were obtained at 30 min postinjection. In 13 patients, FMT uptake in the brain tumor was compared with 18F-fluorodeoxyglucose (FDG). Tumor-to-normal cortex count (T/N) ratio and tumor-to-white matter count (T/W) ratio and SUVs of brain tumors were determined on FMT and FDG PET images., Results: Approximately 1480 MBq (40 mCi) FMT were produced in one radiosynthesis. Percentage injected dose (%ID) of FMT in the brain ranged from 2.8% to 4.9%, and approximately 50%ID of FMT was excreted in urine during 60 min postinjection, of which 86.6% was unmetabolized FMT. A faint physiological brain uptake with SUV of 1.61 +/- 0.32 (mean +/- SD, n = 8) was observed in healthy volunteers. Tumor SUV of FMT ranged from 1.2 to 8.2, with mean value of 2.83 +/- 1.57 (n = 23), which was significantly higher than that of the cortical area in healthy volunteers (P < 0.01). T/N and T/W ratios of FMT were significantly higher than those of FDG (2.53 +/- 1.31 versus 1.32 +/- 1.46, P < 0.001; 3.99 +/- 2.10 versus 1.39 +/- 0.65, P < 0.0001, respectively)., Conclusion: FMT, like other radiolabeled amino acids, can provide high-contrast PET images of brain tumors.

The performance of a high resolution positron emission tomography (PET) system SHR-2000 for animal studies was re-evaluated six years after its installation. The system employs a detector array consisting of BGO crystals that are 1.7 mm (transaxially) by 10 mm (axially) by 30 mm (deep). A block detector, which is a position-sensitive photomultiplier tube (PMT) coupled to 4 arrays of BGO crystals has been adopted to the system. There are 15 block detectors positioned to form a 35 cm diameter ring with a field of view (FOV) of 17 cm by 4.6 cm axially, giving the system a 7 slice imaging capability. For six year workload in spatial resolution (FWHM), there were approximately a 2.6% increase at tangential FOV and a 7.5% increase at radial FOV. In axial resolution (FWHM) there was almost no change. The count rate loss for the true count rate increased 1.3% at 200 kBq/ ml. The average slice sensitivity showed a decrease of approximately 4.1%, and in scatters it showed an increase of approximately 1.4%. In animal experiments, the bones of guinea pigs were clearly identified with 18F fluoride ion. These experiments show that after a six year workload, the system also maintains good performance and has good stability.

Chimeric mouse-human antigranulocyte monoclonal antibody (ch MAb) against non-specific cross-reacting antigen (NCA-95) was labeled with 99mTc (using a direct method) and 125I (using the chloramine T method), and its binding to human granulocytes and LS-180 colorectal carcinoma cells expressing carcinoembryonic antigen on their surfaces, cross-reactive with anti-NCA-95 chimeric monoclonal antibody, increased in proportion to the number of cells added and reached more than 80% and 90%, respectively. In biodistribution studies, 99mTc and 125I-labeled ch anti-NCA-95 MAb revealed high tumor uptake, and the tumor-to-blood ratio was 2.9 after 24 hours. The tumor-to-normal-organ ratio was also more than 3.0 in all organs except for the tumor-to-kidney ratio. Scintigrams of athymic nude mice confirmed the results of biodistribution studies that showed higher radioactivity in tumor and kidney of the mice administered with 99mTc-labeled ch MAb. A normal volunteer injected with 99mTc-labeled ch anti-NCA-95 antigranulocyte MAb showed clear bone marrow images, and a patient with aplastic anemia revealed irregular uptake in his lumbar spine, suggesting its utility for bone marrow scintigraphy and for the detection of hematological disorders, infections, and bone metastasis.

Unlabelled: Various radiopharmaceuticals for breast cancer detection have been used for scintimammography and PET. However, few comparative studies have described the uptake of radiopharmaceuticals as a method of detecting breast cancer. The aim of this study was to assess the radiopharmaceuticals for breast cancer imaging in experimental mice implanted with breast cancer cells., Methods: Six radiopharmaceuticals were studied: three for PET [18F-fluorodeoxyglucose (FDG), L-18F-alpha-methyltyrosine (FMT) and 11C-methionine (C-Met)] and three for scintimammography [99mTc-tetrofosmin (TF), 99mTc-sestamibi (MIBI) and 201Tl-chloride (Tl)]. Biodistributions of six different tracers in mice implanted with MCF-7 breast cancer cells were studied 1 and 3 hr after injection., Results: Tumor uptake 1 hr after injection was FMT = C-Met > FDG = TF > MIBI = Tl. Thallium-201-chloride showed the highest tumor-to-blood ratio (T/B) among all radiopharmaceuticals because of its fast clearance from circulation. The T/B of the six radionuclides used in this study ranged from 1.26 for C-Met to 12.83 for Tl. Tumor-to-muscle ratio (T/M) revealed FMT = C-Met > FDG > MIBI > TF = Tl. The T/M ranged from 0.20 for TF to 2.29 for FMT. Tumor-to-lung ratio (T/L) varied from 0.45 for TF to 2.41 for FMT. FMT revealed the highest T/L of all six radiopharmaceuticals., Conclusion: Among radiopharmaceuticals for PET, FMT seemed to be suitable in detecting MCF-7 tumor; whereas for scintimammography, MIBI, TF and Tl appeared to have almost the same detectability of MCF-7 tumor. The results of this study strongly suggest that FMT may have a potential in breast cancer imaging.

The purpose of this study was to compare positron emission tomography and quantitative digital radiography (QDR) in detecting the effects of aging and diet on bone metabolism. Bone imaging of guinea pigs was performed with fluorine-18 fluoride ions using a high-resolution animal PET system to analyze bone metabolism quantitatively in different age groups of guinea pigs, young (8 weeks), adult (36 weeks), and aged groups (96 weeks), and also in a dietary manipulation group (low calcium and low vitamin D3 diet for 1, 2, and 3 weeks). A three-compartment kinetic model was applied for the analysis of bone metabolism to evaluate the rate constant (K, K1-K4). There was a significant difference in K-constant between the young and other groups. The K-constant was higher (0.100+/-0.005 ml/min/ml) in the young group than in adults (0.028+/-0.001 ml/min/ml) (p < 0.001) and the aged group (0.047+/-0.020 ml/min/ml). This high value of the K-constant in the young group indicates high turnover in bone metabolism, but there was no significant difference between the adult and aged groups. Bone mineral density (BMD) was lower in the young group (0.15+/-0.026 g/cm2) than in the adult (0.230+/-0.021 g/cm2) (p < 0.001) and aged groups (0.26+/-0.03 g/cm2). There was no significant difference in BMD between the adult and aged groups. Although there was no difference in BMD between the control and dietary manipulation groups, PET study revealed a significant difference in K-constant between them (0.028+/-0.001 vs. 0.090+/-0.009 ml/min/ ml) (p < 0.001). The quantitative skeletal dynamic PET study with 18F fluoride ions was more sensitive and superior in the early detection of metabolic disorders in bone disease than QDR.

The effect of lengthening on muscle metabolism was measured and correlated to the percent lengthening at early and late time points. Using the rabbit tibial lengthening model, the authors examined the effects of lengthening on the tibialis anterior muscle using phosphorus-31 magnetic resonance spectroscopy. Thirty-six rabbits were divided into five groups, four groups by percent lengthening (0%, 15%, 20%, and 25%), with each group divided into subgroups of early (end distraction) and late (12 weeks after end distraction), and the fifth group using the opposite untreated leg as control. Several parameters measuring metabolism of muscle using phosphorus-31 magnetic resonance spectroscopy analysis were compared. No changes occurred to 15% lengthening, but significant decreases were measured at 20% and 25% lengthening. After a 25% lengthening, the decreased metabolism persisted at 12 weeks after distraction, indicating the possibility of permanent damage. After 20% lengthening, the same parameters improved but never to normal levels. The authors conclude that lengthening to 15% is safe for muscle, but 20% to 25% lengthening may result in permanent metabolic damage. The current study also suggests that phosphorus-31 magnetic resonance spectroscopy may provide a viable clinical method for evaluating muscle damage during lengthening.

Unlabelled: Iodine-123-alpha-methyl tyrosine has proven to be a promising SPECT agent for imaging amino acid uptake in tumors. We developed L-[3-(18)F]-alpha-methyl tyrosine (FMT) for PET studies. The aim of this study was to investigate its potential use as a tumor-detecting agent by using tumor-bearing mice., Methods: We investigated the biodistribution in normal BALB/C mice and BALB/cA nude mice bearing human rectal cancer cell line (LS180) until 120 min postinjection. FMT tumor uptake at 60 min postinjection in mice with LS180 rectal cancer, RPM11788 B-cell lymphoma and MCF7 mammary cell carcinoma was assessed, and the results were compared with 18F-fluoro-2-deoxy-D-glucose (FDG) tumor uptake. The effect of competitive inhibition of large neutral amino acid transport system using unlabeled L-alanine was also investigated., Results: The amount of FMT in blood fell to 1.05%ID/20 g at 60 min postinjection, whereas that in the pancreas was 15.2%ID/20 g, resulting in a high pancreas-to-blood ratio of 14.5. In other organs, initial uptake peaked at 5 min postinjection and then declined with time. In LS180 tumor-bearing mice, peak FMT uptake in tumor was observed at 60 min postinjection. Tumor-to-blood and tumor-to-muscle ratios ranged from 1.60 to 2.94 and from 2.79 to 3.25 over the 120-min observation period. Tumor uptake of FMT was clearly reduced by inhibition of the amino acid transport system. In mice with LS180 and MCF7 tumors, FMT tumor uptake at 60 min postinjection was significantly higher than FDG tumor uptake, whereas in RPM11788 lymphoma, uptake of FDG was significantly higher than FMT tumor uptake. Tumor-to-blood ratios of FMT in mice with LS180, RPMI1788 and MCF7 tumor at 60 min postinjection were 1.82, 5.88 and 3.56, respectively., Conclusion: FMT, like other fluorinated amino acids, may become a promising tumor-detecting agent for PET, assuming that efficient methods of radiosynthesis are developed.

The aim of this study was to investigate if contrast agents interfere with the performance of an immunoradiometric assay (IRMA) in vitro for serum tumour-associated antigen. Each of five carcinoembryonic antigen (CEA)-positive sera, CA-130-positive sera and tissue polypeptide antigen (TPA)-positive sera was mixed with six contrast agents: Ioversol 350, Iopamidol 370, Iomeprol 300, Iomeprol 400, Iohexol 300 and Gadopenteic acid in 50:50, 50:20, 50:5.0, 50:1.0, 50:0.5 and 50:0.1 microl proportions. Following IRMA, the interference of binding rates in each mixture was calculated, and the serum concentrations of CEA, CA-130 and TPA were estimated and compared with the originals. All contrast agents used were able to inhibit the binding rate with IRMA and the inhibition rates were in proportion to the amount of contrast agent. The detection of serum concentrations of CEA, CA-130 and TPA was significantly inhibited in the mixtures with more than 5.0 microl of contrast agent in all cases. Apart from Iomeprol 400, there was no significant inhibition of detection at the lowest concentrations of contrast agents. Iomeprol 400 was the strongest inhibitor and Gadopenteic acid the weakest inhibitor for each IRMA of the contrast agents employed. In conclusion, our results demonstrate that contrast agents may reduce the immunoreaction of antibody and antigen and lead to in vitro inhibition during immunoassays. It would be unwise to perform any plasma/serum immunoassay on a sample collected within 24 h of the administration of contrast agent considering the pharmacokinetics.

Unlabelled: Indium-111-labeled macroaggregated albumin (MAA) would be suitable for combined pulmonary perfusion and ventilation scan using a 99mTc ventilation agent., Methods: MAA suspended in 0.1 M sodium acetate buffer, pH 5.8, was incubated with 111In-chloride for 30 min at room temperature. An in vitro study of the obtained 111In-MAA was performed for labeling efficiency and stability in human normal serum. The 111In-MAA was intravenously injected into normal mice, and the biodistribution was studied at 15 and 180 min postinjection. A gamma camera image was obtained at 15 min after injection., Results: MAA was directly and stably labeled with 111In-chloride, and the labeling efficiency of the preparation was more than 96%. More than 90% of the administered 111In-MAA was caught in the murine lung. The scintigraphy with 111In-MAA showed a clearly visualized murine lung., Conclusion: Indium-111-MAA can be conveniently prepared by direct labeling at room temperature. It provides an alternative perfusion tracer for combined perfusion-ventilation imaging.

Human macroaggregated albumin (MAA), which is currently labeled with technetium-99m (99mTc) and 99mTc-MAA, is used clinically as a pulmonary perfusion agent and was directly labeled with yttrium-90 (90Y)-acetate. This study evaluated whether 90Y-MAA could be potential radiotherapeutic agent for regional radiotherapy against malignant tumors. MAA suspended in 0.1 M sodium acetate buffer, pH 5.8, was incubated with 90Y-acetate and purified in order to get rid of unstable binding of 90Y by electrophoresis. The radiochemical purity of 90Y-MAA in normal human serum was estimated by an agarose electrophoresis method and was more than 94% over 168 h in vitro. Following the intratumoral administration of 90Y-MAA, the time course of tumor radioactivity and the biodistribution in nude mice bearing human neuroblastoma were investigated up to 168 h. More than 93% of the radioactivity of the injected dose was found on the subcutaneous tumor over 168 h. The bone radioactivity was shown as 0.06 +/- 0.03% injection dose/gram tissue (% ID/g) (n = 5) at 24 h, 0.73 +/- 0.20% ID/g at 72 h, 0.92 +/- 0.16% ID/g at 120 h, and 2.51 +/- 0.59% ID/g at 168 h. A slight increase in radioactivity was noted in the liver, kidneys, and spleen over the 168-h periods. In conclusion, 90Y-MAA may be a potential agent for regional radiotherapy (brachytherapy) because of the sufficient persistence in the tumor following an intratumoral administration.

Unlabelled: We compared myocardial viability evaluated by 18F-deoxyglucose (FDG) SPECT in 14 old myocardial infarction patients with that evaluated by 201TI SPECT and 123I-beta-methyl-iodophenyl pentadecanoic acid SPECT as imaging of fatty acid metabolism. FDG-SPECT was performed after oral administration of glucose. From each SPECT image which was divided into 7 segments, the degree of accumulation of each radioisotope (RI) was visually classified into four grades of defect score (ranging from 0 as normal to 3 as severe defect). The % uptake in the same area was also quantitatively calculated., Results: The degree of accumulation of myocardial Rl relative to regional wall motion. FDG is the most wide for a range of accumulation of Rl of infarct area. Also, at FDG, in the area of wall motion had done a disorder, the degree of accumulation was higher than other two methods. In the infarcted area, the degree of accumulation on FDG-SPECT in the area of decreased wall motion was greater than that on the other two procedures. These results suggest that FDG-SPECT is useful for evaluating myocardial viability.

To diagnose cancers with radiolabelled amino acid using positron emission tomography, we have constructed a separation and purification system for the production of L-18F-alpha-methyltyrosine (L-18FAmT). This system could provide radioprotection and consistent production of L-18FAmT. L-18FAmT was synthesized and purified and the efficiency of the system was examined. The radiochemical yield of L-18FAmT was 20.3 +/- 5.1% (n = 5) based on the radioactivity trapped in the reaction vessel. The radiochemical purity was greater than 99.4 +/- 0.3% (n = 5). The radiochemical stability in phosphate-buffered saline and human plasma was examined and little decomposition was observed by HPLC analysis. Our results indicate that the separation and purification system gave simple and quick synthesis of L-18FAmT with a large reduction in radiation exposure and consistent production of L-18FAmT.

Purpose: The objective of the present study was to test, in nude mouse PC-3 tumors, the contrast enhancement of 2,4-bis(1-tetrahydro-fulfuroxyethyl)-deuteroporphynyl(IX)-6- 7-bisaspartic acid (THF-Mn-ASP), which is a hematoporphyrin derivative and depresses T1 relaxation time on magnetic resonance (MR) imaging., Materials and Methods: THF-Mn-ASP or gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) was intravenously administered, and MR imaging of the tumors transplanted into nude mice was performed on T1-weighted images., Results: After administration of THF-Mn-Asp, the signal intensity of PC-3 tumors increased and the tumor/muscle intensity ratio was highest at about 1 hour. The tumor/muscle intensity ratio, in contrast, was highest at about 5 minutes after administration of Gd-DTPA. The increase in intensity ratio was 32% in THF-Mn-ASP and 28% in Gd-DTPA., Conclusion: The preliminary study suggested that THF-Mn-Asp has a predilection to accumulate in PC-3 tumors, and it seems to provide good contrast enhancement with tumor specificity for MR imaging.

The purpose of this study was to evaluate the accuracy of myocardial imaging by means of high-resolution single-photon emission tomography (SPET) with a pinhole collimator in rats with experimental infarction. Myocardial infarctions were induced in male Wistar rats by ligation of the left coronary artery for 30 min, followed by reperfusion. Two days after the reperfusion, pinhole SPET was performed after the intravenous administration of 111 MBq of thallium-201 chloride, using a rotating gamma camera equipped with a pinhole insert (2.0-mm aperture) in a low-energy pinhole collimator. SPET projection data were collected at 6 degrees increments over 360 degrees using a 4-cm radius of rotation to reconstruct the short- and long-axis images. Projection data were acquired in 15 or 30 s, the SPET imaging being accomplished within 40 min after the injection of 201Tl. After SPET, the rats were sacrificed to remove the hearts for autoradiography (ARG) and nitroblue tetrazolium (NBT) staining as a visual correlative study. Quantitative correlative studies between pinhole SPET and ARG were performed with linear regression analysis for infarct size and distribution properties (relative counts on SPET images and relative density on autoradiographs) on the short-axis sections. All infarcts (4 mm in minimum diameter) in seven rats were detected by pinhole SPET. The SPET images in rats with or without myocardial infarction were consistent with the findings of ARG and NBT staining. There were significant correlations between pinhole SPET and ARG with respect to the infarct size (r=0.933, P <0.001; n=15) and the relative radiotracer distribution (r=0.931, P <0.001; n=68). This study therefore confirmed the accuracy of myocardial pinhole SPET imaging in rats with myocardial infarction. This method may partially substitute for ARG and prove useful for assessing new myocardial imaging agents in vivo in small laboratory animals.

Fluorine-18-fluorodeoxyglucose (18F-FDG) single photon emission CT(SPECT) imaging was performed in four patients with malignant neoplasms. Acquisition of SPECT was started 40 minutes after intravenous administration of 370MBq of 18F-FDG using dual-headed gamma camera equipped with 511keV collimators. Whole body planar scintigraphy was also obtained after the SPECT study. Tumor uptake of 18F-FDG was detected in three of four patients on both SPECT and planar images, and a 2.5 x 1.5 cm lung tumor was clearly visualized on SPECT image. Excellent SPECT image of 18F-FDG using a conventional gamma camera system is promising for the wide use of this system in cancer diagnosis.

It is ideal to perform a simultaneous pulmonary perfusion and ventilation scan in cases of suspected pulmonary thromboembolism. Indium-111 (111In)-diethylenetriaminepentaacetic acid (DTPA)-macroaggregated albumin (MAA) was designed for this purpose. MAA was conjugated with DTPA at a molar ratio of 1:100 and incubated with 111In-chloride for 30 min at room temperature. DTPA-MAA could be labelled with 111In above a 96% labelling efficiency without MAA particle aggregates making their particles larger than desirable. The obtained 111In-DTPA-MAA was intravenously injected into normal mice and their biodistribution was studied at 15 and 180 min after injection. A gamma camera image was obtained 15 min after injection. 111In-DTPA-MAA was stable in vitro and in vivo, and gave high uptake of murine lung in the biodistribution study and clearly visualized murine lung in the scintigraph. Using 111In-DTPA-MAA as a pulmonary perfusion agent, a simultaneous pulmonary perfusion and ventilation scan with technetium-99m-ventilation agents is able to be performed using the dual-isotope technique. 111In-DTPA-MAA may be a potential pulmonary perfusion agent.

A new immunoradiometric assay kit (IRMA) of human serum tissue polypeptide antigen (TPA) based on combination monoclonal antibodies was evaluated. Using a new TPA-IRMA, the procedure of TPA measurement was faster and the range of measurement was more wide than a conventional TPA-IRMA. 89% (76/85 cases) of patients with malignant tumor and 96.4% (27/28) of patients with metastatic malignant tumor were positively detected. This assay of new TPA-M kit is sensitive to the level of serum TPA which is corresponding to a therapy. It is concluded that a new TPA-IRMA is very useful in monitoring and assessing malignant tumors.

Unlabelled: SPECT with 201TI is an effective procedure for evaluating the malignancy of glioma. Our goal was to investigate the diagnostic relevance of both 201TI SPECT and [18F]fluorodeoxyglucose (FDG) PET and the relation between 201TI uptake and glucose metabolism in glioma using comparative SPECT and PET studies., Methods: Thallium-201 SPECT and FDG dynamic PET studies were performed in 20 patients with untreated glioma (5 with glioblastoma, 5 with anaplastic glioma, 10 with low-grade glioma). Thallium-201 uptake in the tumor was estimated using the 201TI index, defined as the ratio of 201TI uptake in the tumor to that in the contralateral normal brain on SPECT images obtained 15 min after intravenous injection. We measured regional glucose metabolic parameters, including rate constants and regional cerebral metabolic rate of glucose utilization (rCMRgl), in the tumor. We then compared the regional 201TI index and glucose metabolic parameters with the histologic characteristics, malignancy and computed tomographic/ magnetic resonance imaging findings. In addition, we investigated the correlation between the 201TI index and glucose metabolic parameters., Results: Thallium-201 SPECT showed abnormal 201TI uptake in all patients with glioblastoma and anaplastic glioma. Thallium-201 indices of glioblastoma (202.6 +/- 22.1%) and anaplastic glioma (176.6% +/- 26.6%) were significantly higher than that for low-grade glioma (106.7% +/- 13.8%). The rCMRgl value of glioblastoma (17.6 +/- 3.5 mumole/100 g/min) was also significantly higher than that for low-grade glioma (10.8 +/- 4.5 mumole/100 g/min), although rCMRgl showed a large variability in both high- and low-grade glioma. Rate constants of FDG kinetics had no correlation with histological grade of glioma. Some patients with high-grade glioma, however, showed false-negative results with FDG-PET because of high normal brain uptake of FDG. Conversely, most low-grade glioma could not be localized by 201TI SPECT. There was no correlation between the 201TI index and glucose metabolic parameters., Conclusion: Thallium-201 indices and rCMRgl values for glioblastoma were higher than those for low-grade glioma. Thallium-201 uptake in the tumor may be independent of increased glucose transport or metabolism. Thallium-201 SPECT and FDG-PET are complementary in the diagnosis of glioma, although 201TI SPECT is more significantly correlated with the malignancy of glioma.

A stripe sign in pulmonary perfusion imaging is reported to be predictive of the absence of pulmonary embolism in the specific area of the stripe sign, and generally does not change on serial pulmonary perfusion imaging. The authors present the case of a patient with a stripe sign that disappeared on serial perfusion imaging without a ventilation abnormality. A "changing stripe sign" may raise suspicion for the possible existence of acute pulmonary embolism.

PET imaging studies with 4-[18F]fluoro-L-m-tyrosine (FMT) in normal macaca monkeys showed selective accumulations of radioactivity in the striatum with time. In monkeys rendered hemiparkinsonian by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), FMT uptake was eliminated in the lesioned striatum. FMT-PET studies were able to detect dopaminergic terminals in both normal and hemiparkinsonian monkeys, and clearly showed a reduction in aromatic L-amino acid decarboxylase (AAAD) activities in the MPTP-lesioned striatum. These results show that FMT is promising as a PET tracer for the evaluation of central dopaminergic systems in parkinsonism.

TRAb Dade kit is a radioreceptor assay that detects autoantibodies in serum of patients with thyroid diseases which interfere with the binding of 125I labeled TSH to its receptor. In this paper we examined the basic and clinical usefulness of newly developed TRAb assay kits. The intra and inter assay coefficients of variation were 7.9% and 8.4%, respectively. There was no significant effect of temperature and incubation time on TRAb values. The influence of conjugated, unconjugated bilirubin, hemoglobin and turbidity was not so significant on TRAb values. TRAb values in serum of 68 untreated Graves' disease were above the normal range, but most (78%) treated Graves' patients who became euthyroid after receiving antithyroid drug, showed the normal range. In patients with chronic renal failure TRAb values were also within the normal range. A significant correlation (y = 1.0x-0.88, r = 0.95) was observed between this TRAb kit and TRAb Cosmic values in various thyroid conditions. This new assay for TRAb was simple, rapid and reproducible. The measurement of serum TRAb values was useful for the evaluation of physiological and pathological function and seemed to be helpful in the management of patients with thyroid disease.

A superior vena cava syndrome was caused by venous thrombosis of both proximal subclavian veins. Collateral pathways were clearly demonstrated by radioisotope venography. Indium-111 labeled platelet thrombography was useful in localizing thrombotic lesions.

The safety, pharmacokinetics and dosimetry of the somatostatin analog 111In-DTPA-D-Phe-octreotide (111In-octreotide) were investigated in four young normal volunteers as phase 1 study in Japan. Neither adverse reactions nor significant changes of vital signs and clinical laboratory data were observed after intravenous injection of 111 MBq of 111In octreotide. The plasma clearance curve consisted of fast and slow exponential components with mean half life of 9.2 minutes and 2.2 hours, respectively. Seventy three percent of the injected dose were excreted in the urine by 24 hours after the injection of 111In-octreotide. With respect to the radiation dose to normal tissue, the most important organs were the urinary bladder, the kidney, the spleen and the liver. The effective dose equivalent was calculated as 3.26 +/- 0.43 mSv/37 MBq (mean +/- s.d.). This phase 1 study demonstrated the safety of scintigraphy with 111In-octreotide.

Serum levels of cytokeratin subunit 19 (CYFRA 21-1) were measured in 42 healthy volunteers, 104 cases of malignant diseases, 30 patients with chronic renal failure and 13 patients with nonmalignant and infectious diseases. The reliability of the method was demonstrated after dilution of serum samples and intra- and inter-assay reproducibility. Serum CYFRA-21-1 concentrations were less than 2.00 ng/ml in all healthy controls and 86% of the malignant cases had high serum CYFRA 21-1 levels. However slightly elevated values of CYFRA 21-1 were observed in most chronic renal failure patients. High correlation was observed between serum CYFRA 21-1 and Tissue Polypeptide Antigen (TPA) values (r = 0.90, n = 10) but not with serum alpha-feto protein (AFP) concentrations. Furthermore, cross binding tests with the CYFRA 21-1 tracer/CYFRA 21-1 antibody-coated beads and CYFRA 21-1 tracer/TPA antibody-coated beads also gave an almost linear graph. These results indicate that CYFRA 21-1 and TPA share similar type of antigens.

An enlarged spleen failed to accumulate Tc-99m-labeled phytate, but it showed normal perfusion and uptake of labeled and heat-denatured red blood cells. A blood cell count demonstrated moderately low hemoglobin and hematocrit levels and a markedly low platelet count, and results of direct Coombs' and antiplatelet-antibody (IgG) tests were positive. Steroid therapy resulted in normal splenic function. This case demonstrates reversible functional asplenia caused by reticuloendothelial dysfunction secondary to pure splenic chronic lymphocytic leukemia.

We describe a simple method of pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] preparation for the imaging of medullary carcinoma of the thyroid using commercially available kits. 99mTc(V)-DMSA is available at high pH (approximately 7.5) by adding NaHCO3 solution in the presence of a small amount of reducing agent (SnCl2). On the other hand, trivalent 99mTc-DMSA [99mTc(III)-DMSA] can be obtained at low pH (below 3) in the presence of an excess amount of reducing agent. In the clinical evaluation of a patient with a medullary carcinoma of the thyroid, only 99mTc(V)-DMSA revealed an area of intense accumulation.

4-[18F]Fluoro-L-m-tyrosine (FMT) is an L-Dopa analog that essentially follows the L-Dopa metabolic pathway, but without 3-O-methylation or extensive peripheral metabolism. As such, FMT may serve as a useful probe of striatal dopaminergic function with positron emission tomography (PET). FMT was synthesized, as previously described by Perlmutter et al. [Appl Radiat Isot 1990;41:801-807]. Scanning was undertaken with the SHR2000 positron tomograph (image spatial resolution, 3.5 x 4.5 x 6.5 mm). Two Macaca monkeys were anesthetized with ketamine (10 mg/kg) and pentobarbital (20 mg/kg). FMT was administered intravenously (5-6 mCi; specific activity 1-2 Ci/mmol) following carbidopa pretreatment (5 mg/kg i.v., 60 min before FMT administration). Dynamic image acquisition was done for 2 h immediately after tracer injection. This emission acquisition involved twelve 2-min frames followed by nine 4-min frames, and six 10-min images. Arterial blood samples were collected according to a schedule for assay of plasma [18F] radioactivity. Specific uptake of FMT in aromatic L-amino-acid-decarboxylase-rich areas of the monkey striatum was observed with PET imaging. The striatum-to-cerebellum ratio of the accumulation increased over time to 3.0 at 2 h. These results show the promise of FMT as a PET tracer in evaluating the CNS dopaminergic system.

We performed 201Tl SPECT and cell kinetic studies on 28 presurgical patients with supratentorial gliomas by administering bromodeoxyuridine (BUdR). All patients had surgery and had follow-up for more than 25 mo. In patients with grade IV glioma (198.1% +/- 32.8%, n = 10), the 201Tl index, expressed as the count rate of the tumor site to the count rate over the contralateral normal region, was significantly higher than that in patients with grade III glioma (140.5% +/- 15.1%, n = 4, p < 0.01) or low-grade glioma (104.1% +/- 22.6%, n = 14, p < 0.001). A significant correlation was observed between the 201Tl index and BUdR-positive cells in excised tumor specimens (r = 0.67, p < 0.001). The 201Tl index of the 12 patients who died was higher than those who survived (173.2% versus 122.4%, p < 0.01). These results show the clinical utility of 201Tl brain SPECT in imaging supratentorial glioma and that the 201Tl index is representative of proliferative activity of the tumor.

"SD-8729" is a one-step IRMA kit employing OC125 antibody as 125I-labeled tracer and M-11 antibody as an immunoadsorbent. Higher bound-radioactivity to beads was observed with shorter incubation time than that of a currently used CA125 IRMA kit which employed OC125 antibody both as 125I-labeled ligand and immunoadsorbent attached to beads. Almost identical CA125 values were obtained by using two kits. The antigenic nature recognized by the M-11 antibody seems substantially different from those of 130-22 or 145-9 antibodies recognizing CA130 antigen.

We performed basic and clinical studies of IRMA "BL-CA195" kit in which monoclonal antibody CC3C195 was used as 125I-labeled tracer and solid phase antibody. The reproducibility of the assay results and dilution curves were satisfactory. There was a close correlation between serum CA195 and CA19-9 values, and many patients with pancreatic and colorectal cancer had elevated serum CA195 concentrations. Unlabeled CC3C195 antibody dose-dependently and completely inhibited the binding of 125I-labeled anti-CA19-9 antibody to its corresponding antigen. These findings suggest that CA195 and CA19-9 share common antigenic determinants.