Crossover study of (99m)Tc-TRODAT-1 SPECT and (18)F-FDOPA PET in Parkinson's disease patients.

99mTc-TRODAT-1 ([2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)]) is a potential agent for dopamine transporter (DAT) SPECT, whereas 6-(18)F-fluoro-L-dopa ((18)F-FDOPA) PET has been used for the quantitative assessment of presynaptic nigrostriatal dopaminergic function. The current study investigated the relationship between the 2 imaging modalities in evaluating patients with Parkinson's disease (PD). METHODS: Twenty patients in whom PD was diagnosed by generally accepted criteria were recruited. In addition to visual inspection, specific uptake ratios (SURs) of (99m)Tc-TRODAT-1 in the striatum and putamen were measured bilaterally. For PET, all patients received 100 mg of carbidopa 90 min before (18)F-FDOPA (300 MBq) injection. Images were acquired between 120 and 150 min after injection, using a whole-body PET scanner with settings identical to those for the SPECT studies. The SURs for PET were calculated similarly to those for SPECT. Individual SURs of the striatum or putamen from SPECT were correlated with the corresponding PET values using linear regression. RESULTS: A consistent image pattern between SPECT and PET was achieved by visual inspection except for 3 cases. In 1 case (a patient with Hoehn and Yahr Scale I PD), the SPECT images were more compatible with the patient's clinical findings whereas PET showed nearly normal uptake. In the other 2 cases (both patients with Hoehn and Yahr Scale II PD), PET correlated better with the clinical findings. The caudate and putamen nuclei were more discernable on PET. An acceptable correlation of SUR, however, was found between SPECT and PET in both the striatum and the putamen (P < 0.01 for both). CONCLUSION: The comparability of (99m)Tc-TRODAT-1 SPECT and (18)F-FDOPA PET suggests that (99m)Tc-TRODAT-1 SPECT may provide a reliable alternative to (18)F-FDOPA PET in the evaluation of clinical PD patients.     

99m Tc-TRODAT-1动物体内生物学分布特性的实验研究

目的:探讨国内研制的“一步法”药盒标记的多巴胺转运蛋白(DAT)显像剂99mTc-TRODAT-1在动物体内的生物学特性和显像效果。方法:①“一步法”药盒生产标记物;②正常大鼠体内生物分布特性的实验;③正常猴和偏侧PD模型猴给药后3h脑SPECT显像。结果:①TRODAT-1药盒标记简便。经TLC检测,标记率为79.9%,室温下放置2.5h稳定;②正常大鼠体内放射性清除迅速,主要由肝脏代谢后经肠道排出体外;③99mTc-TRODAT-1脑内浓聚较低,但纹状体(ST)区放射性摄取快速且保留较好,小脑(CB)清除较快,ST/CB值于2h达峰值(ST/CB=3.21),持续4h;④纹状体对99mTc-TRODAT-1的特异性摄取不受预先注射的氟哌啶醇的影响;⑤99mTc-TRODAT-1在大鼠体内分布无性别差异;⑥猴脑DATSPECT显像能基本清晰显示双侧ST正常影像及其病理改变。ST/CB值可以作为反映ST特异性摄取的参数指标。结论:“一步法”药盒制备的99mTc-TRODAT-1可用于脑SPECT显像研究,显像时间取给药后2~3h时间段为宜。     

99Tc(m)-ECD SPET perfusion changes by internal pallidum stimulation in Parkinson's disease

High-frequency stimulation of the internal pallidum is an effective surgical approach for patients with advanced Parkinson's disease suffering from motor fluctuations and L-dopa induced dyskinesia. To study the acute effects of internal pallidum stimulation, changes in cerebral blood flow were measured by means of a single-day split-dose protocol using 99Tc(m)-ECD SPET. Nine patients with advanced Parkinson's disease and with a clinical picture predominated by tremor and drug-induced dyskinesia, were imaged before and immediately after electrostimulation. Brain perfusion data were mirrored to the same electrode side (five left and four right implants), co-registered and analysed statistically on a voxel-by-voxel basis (Statistical Parametric Mapping) and by an automated volume-of-interest approach. Acute stimulation of the internal pallidum induced a significantly decreased perfusion in the ipsilateral thalamus and striatum, as well as in the right parietal cortex. For the subgroup of seven patients with effective motor score improvements, a significant correlation between thalamic and striatal perfusion changes and UPDRS III motor score was present (P = 0.04). These results suggest that effective stimulation of the internal globus pallidus may produce symptom relief through decreased activity in pallido-thalamo-cortical circuits.     

The utility of (99m)Tc-DMSA and Tc(99m)-EC scintigraphy for early diagnosis of ifosfamide induced nephrotoxicity.

A serious undesired effect of certain cytostatics is their nephrotoxicity. In this study, we investigated the toxic effects of ifosfamide and cisplatin by clinical and biochemical parameters in relation to (99m)Tc-dimercaptosuccinic acid ((99m)Tc-DMSA) and Tc(99m)N, N-ethylenedicysteine (EC) renal scintigraphy. The indicators were urinary beta2-microglobulin levels, tubular resorption of phosphate, urinary protein and glucose excretion, glomerular filtration rate, urinary pH and osmolarity. Thirteen paediatric patients (seven boys and six girls), aged 2-16 years, were investigated. Five patients received only cisplatin, six patients were treated with ifosfamide and cisplatin and two with ifosfamide and carboplatin for various malignancies. All except three patients had normal DMSA uptake (median, 19; range, 16-29%) prior to chemotherapy. The reduction in DMSA uptake was unilateral due to tumour invasion in those three patients. Following chemotherapy, DMSA uptake showed reduction in five patients with or without clinical nephrotoxicity. The observed pattern was decreased renal uptake and elevated bladder activity. Three patients with decreased DMSA uptake had normal tubular maximum phosphate reabsorption, which suggested subclinical injury. Decrease in DMSA uptake and tubular phosphate reabsorption (TPR) was detected simultaneously in two patients. No abnormalities were seen on Tc(99m)-EC scintigraphy to suggest nephrotoxicity in our investigation. However, Tc(99m)-EC clearly demonstrated a reduction in split renal function in children with tumour invasion. In summary, we found that ifosfamide induced tubular injury can be detected with (99m)Tc-DMSA scintigraphy before chemotherapy associated nephrotoxicity is observed by laboratory measurements. Our results also imply that, although a tubular agent, renal scintigraphy performed with Tc(99m)-EC is not able to detect subclinical injury or predict the outcome during treatment.     

Direct 99m Tc labeling of Herceptin (trastuzumab) by 99m Tc(I) tricarbonyl ion.

By simply incubating Herceptin (trastuzumab) with [99m Tc(CO)3(OH2)3]+ ion in saline, a significant yield of 99m Tc-labeled trastuzumab was found to be achievable. The effective labeling may be based on that trastuzumab is inherent with endogenous histidine group to which 99m Tc(I) tricarbonyl ion can be strongly bound. For practical 99m Tc labeling processing, trastuzumab was purified beforehand from the commercial product, Herceptin (Genentech) via size exclusion chromatography to remove the excipient, alpha-histidine and a high-labeled yield could be obtained by incubating the purified trastuzumab with [99m Tc(CO)3(OH2)3]+. Retention of bioactivity of the 99m Tc(I)-labeled trastuzumab was validated using a cell binding test.     

Alteration of the organ uptake of the (99m)Tc-radiopharmaceuticals, (99m)Tc-DPD, (99m)Tc-DMSA, (99m)Tc-tin colloid and (99m)Tc-MAA, induced by the applied cytotoxic drugs methotrexate sodium and cyclophosphamide

AIM: To investigate the influence of certain cytotoxic drugs on the organ uptake of the following (99m)Tc-radiopharmaceuticals: (99m)Tc-2,3-dicarboxypropane-1,1-diphosphonic acid ((99m)Tc-DPD), (99m)Tc-meso-2,3-dimercaptosuccinic acid ((99m)Tc-DMSA), (99m)Tc-tin colloid and (99m)Tc-macroaggregated albumin ((99m)Tc-MAA). Methotrexate sodium and cyclophosphamide were used as models to evaluate these effects. METHODS: Two groups of healthy male Wistar rats were treated separately by oral application of the drugs for 7 days. On the eighth day, each of the (99m)Tc-radiopharmaceuticals was applied in a separate group of treated animals. They were sacrificed at different time intervals and the radioactivity in the organs of interest was measured. The organ uptake of the (99m)Tc-radiopharmaceuticals in an additional control group of animals was also studied. RESULTS: The results obtained showed an alteration in the organ uptake of (99m)Tc-radiopharmaceuticals in animals treated with cytotoxic drugs. In rats treated with methotrexate sodium, there was a higher uptake of (99m)Tc-DMSA in the bones, stomach and intestine, a higher uptake of (99m)Tc-DPD in the bones, intestine, blood and muscle, a lower uptake of (99m)Tc-tin colloid in the liver and a lower accumulation of (99m)Tc-MAA in the lungs. Cyclophosphamide-treated animals showed enhanced uptake of (99m)Tc-DMSA in the kidneys, a twofold enhanced uptake of (99m)Tc-DPD in all organs except the stomach, a decreased uptake of (99m)Tc-tin colloid in the lungs, spleen and kidneys and a significantly decreased uptake of (99m)Tc-MAA in the lungs. CONCLUSION: These results confirm that both methotrexate sodium and cyclophosphamide may alter the organ uptake of (99m)Tc-radiopharmaceuticals in experimental animals.     

Evaluation of early-stage Parkinson's disease with 99mTc-TRODAT-1 imaging.

Parkinson's disease is a progressive neurodegenerative disorder characterized by a selective loss of dopamine in the striatum. Problems remain in the accurate diagnosis of Parkinson's disease. A 99mTc-labeled tropane derivative that binds to dopamine transporter with high selectivity is [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)] (TRODAT-1). The purpose of this study was to investigate the potential usefulness of 99mTc-TRODAT-1 imaging in the evaluation of patients with early-stage Parkinson's disease. METHODS: Thirty-four patients with early-stage idiopathic Parkinson's disease were recruited. For all patients, the Parkinson's disease was stage 2 or less as assessed by the Hoehn and Yahr scale. Seventeen age-matched healthy volunteers (8 men, 9 women) served as controls. 99mTc-TRODAT-1 was prepared from a lyophilized kit. Brain SPECT imaging was performed between 165 and 195 min after injection, using a double-head camera equipped with fanbeam collimators. Specific uptake in the striatum and its subregions, including the putamen and caudate nucleus, was calculated and compared with that of the other sides and of healthy volunteers. RESULTS: A continuous reduction in specific striatal uptake of 99mTc-TRODAT-1 with increasing disease severity was found in Parkinson's disease patients (control vs. stage I vs. stage II, 1.98 vs. 1.62 vs. 1.22, respectively, P < 0.01). The changes were magnified by measurement of specific putaminal uptake (control vs. stage I vs. stage II, 1.81 vs. 1.27 vs. 0.94, respectively, P < 0.01). The mean values of specific putaminal uptake contralateral to the more affected limbs were significantly decreased compared with the ipsilateral sides in both stage I and stage II groups (1.02 vs. 1.49 for stage I and 0.73 vs. 1.14 for stage II, P < 0.01). Moreover, a significant loss of putaminal uptake ipsilateral to the symptoms was found in the stage I group compared with the healthy volunteers (1.49 vs. 1.81, P < 0.01). The difference became greater when the posterior putaminal uptakes were compared. No remarkable adverse reactions were found in either healthy volunteers or Parkinson's disease patients during or after imaging. CONCLUSION: For clinical practice, 99mTc-TRODAT-1 may serve as a useful imaging agent for the early detection of Parkinson's disease.     

99mTc-MAEC complexes: new renal radiopharmaceuticals combining characteristics of (99m)Tc-MAG3 and (99m)Tc-EC.

99mTc-Mercaptoacetyltriglycine ((99m)Tc-MAG3) and (99m)Tc-L,L-ethylenedicysteine ((99m)Tc-LL-EC) are useful renal radiopharmaceuticals; however, both agents have renal clearances less than that of (131)I-orthoiodohippurate ((131)I-OIH), and (99m)Tc-LL-EC exists in dianionic and monoanionic forms at physiologic pH. In an effort to develop a superior (99m)Tc agent with a rapid clearance comparable with that of (131)I-OIH, we have designed a new ligand system, mercaptoacetamide-ethylene-cysteine (MAEC), which combines important structural features of both MAG3 and EC. METHODS: Biodistribution and clearance studies were performed on Sprague-Dawley rats using syn- and anti-(99m)Tc-L- and -D-MAEC coinjected with (131)I-OIH. Studies were also performed by coinjecting each isomer ( approximately 74 MBq [ approximately 2 mCi]) and 7.4-11.1 MBq (200-300 micro Ci) of (131)I-OIH in 3 volunteers with dual-isotope imaging performed using a camera system fitted with a high-energy collimator. Blood samples were obtained from 3 to 90 min after injection and urine samples were obtained at 30, 90, and 180 min. RESULTS: In the rats, <10% of the injected dose remained in the blood at 10 min after injection for all isomers, and the urine dose at 60 min ranged from 84% to 99% that of (131)I-OIH. The clearances of syn- and anti-(99m)Tc-L-MAEC in the rats were higher than the clearances for the D-isomers (P 相似文献   

In vitro adsorption of 99Tc(m)-MIBI, 99Tc(m)-tetrofosmin, 99Tc(m)-furifosmin and 99Tc(m)O4- onto tubes

Adsorption of radiopharmaceuticals onto disposable syringes has been reported to amount to levels of almost 50%. Data on adsorption of radiopharmaceuticals onto materials used for in vitro studies are extremely limited. We assessed the extent of adsorption of 99Tc(m) hexakis(2-methoxyisobutylisonitrile) (99Tc(m)-MIBI), 99Tc(m)-tetrofosmin, 99Tc(m)-furifosmin and 99Tc(m)O4 onto tubes used for in vitro measurement of cellular uptake of these radiopharmaceuticals. The influence on adsorption of different incubation media, temperature and time of incubation was evaluated. Total (not corrected for adsorption) uptake was compared with corrected, net cellular uptake in SK-BR-3, MCF-7 and liposarcoma cell lines. Values of adsorption ranging from 0.94+/-0.13% to 7.07+/-0.46% were found. The extent of adsorption of all the radiopharmaceuticals varied with the type of incubation medium and the incubation temperature. With 99Tc(m)-furifosmin, adsorption was dependent on the incubation time as well on the incubation temperature and some of the incubation media investigated. Our findings indicate that systematic investigations to evaluate the adsorption of radiopharmaceuticals onto materials used during in vitro studies of cellular uptake should be considered a mandatory aspect of quality control.     

Differential diagnosis of jaundice by 99mTc-IDA hepatobiliary imaging.

The utility of 99mTc-IDA imaging in the differential diagnosis of jaundice was assessed. Although overall accuracy was 84%, this method is still inferior to the reported efficiency of ultrasonography and CT in making the correct diagnosis. Radionuclide imaging is a good alternative when these other modalities are not available and it functions well in an adjuvant capacity. The diagnostic limitations of 99mTc-dimethyl IDA imaging in cases of moderate to severe jaundice are largely overcome by the use of 99mTc-p-butyl IDA.     

Evaluation of the stability of (99m)Tc-ECD and stabilized (99m)Tc-HMPAO stored in syringes.

OBJECTIVE: To determine and compare the stability of (99m)Tc-ECD and stabilized (99m)Tc-HMPAO when stored in syringes over an 8-h period. METHODS: (99m)Tc-ECD and stabilized (99m)Tc-HMPAO were prepared according to the manufacturers' protocols, with the following exception: eluate less than 60 min old was used to prepare (99m)Tc-HMPAO rather than the recommended 30 min. Once prepared, 185 MBq (5 mCi) of both products were drawn into 5-mL syringes and allowed to sit at room temperature. At 2, 4, 6, and 8 h after preparation, the radiochemical purity (RCP) of the contents of the syringes was determined and compared to the RCP of the products in vials. Retention of activity of each product in syringes was also evaluated by measuring activity remaining in each syringe (and filter, in the case of (99m)Tc-HMPAO) after expressing its contents. RESULTS: The RCP of stabilized (99m)Tc-HMPAO stored in syringes decreased from a mean of 87.7% at 2 h to 74.0% at 8 h after preparation. In contrast, (99m)Tc-ECD retained an RCP of greater than 94% throughout the time tested. The impurity that appeared to increase over time with (99m)Tc-HMPAO was found to be sodium pertechnetate. Total retention of activity remaining in the syringe and filter ranged from 11.6% at 2 h to 9.5% at 8 h for (99m)Tc-HMPAO; the syringe itself retained less than 5% of the total activity at all time periods. (99m)Tc-ECD exhibited 6.2% to 11.3% retention of activity in the syringe. The sorption of sodium pertechnetate to the syringe for the same time period was less than 1%. CONCLUSIONS: (99m)Tc-ECD is a more stable product than stabilized (99m)Tc-HMPAO in a syringe. Both products demonstrate retention of radioactivity in the syringe. Some of this retention may denote sorption of the products to plastic.     

Autosomal recessive (infantile) polycystic kidney disease demonstrated by Tc-99m DMSA renal imaging.

A neonate with infantile polycystic kidney disease underwent Tc-99m DMSA imaging. The pattern of uptake in infantile polycystic disease is different from the multiple cystic lesions reported in the literature for adult polycystic kidney disease. The infantile pattern of uptake shows large kidneys with diffuse, symmetric localization of the radiopharmaceutical, which seems to be characteristic and may be pathognomonic of the disease process.     

Cognition and 99Tcm-HMPAO SPECT in Parkinson's disease.

99Tcm-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) of brain was performed in 43 unselected patients with Parkinson's disease to evaluate whether low cerebral perfusion on SPECT correlated with cognitive impairment in the patients. All patients received neurological, Mini-Mental State Examination and a neuropsychological assessment. Eighteen (41.9%) of the 43 patients were demented. Thirty patients (69.8%) had abnormal SPECT: 17 had perfusion defects in cortical regions, eight in basal ganglia and five in both regions. Of the 22 patients with abnormal cortical perfusion, 15 (68.2%) were demented; only three (14.3%) of the 21 patients without cortical defect were demented (P < 0.01). Twelve of the 15 demented patients had low perfusion in the parietal region alone or in parietal and occipital regions. The cortical perfusion defects, present in 22 (51.2%) Parkinson's patients, are highly correlated with cognitive impairment. The pattern of SPECT abnormality in most demented patients with Parkinson's disease is similar to that seen in Alzheimer's disease, suggesting that the underlying pathophysiology for dementia in patients with Parkinson's disease may be similar to that in Alzheimer's disease.     

Lymphoscintigraphy: a comparison of 99Tc(m) antimony sulphide colloid and 99Tc(m) stannous phytate.

In vitro comparison of 99Tc(m) antimony sulphide colloid and 99Tc(m) stannous phytate as well as in vivo studies in six rabbits and seven patients indicate disparity in the colloidal properties and localization of these two agents. The variability in lymphatic uptake and the relatively poor quality of scintigraphic images following interstitial injection of 99Tc(m) stannous phytate, when compared with 99Tc(m) antimony sulphide colloid, provide evidence of the unsuitability of this agent for lymphoscintigraphy. Maintenance of the diagnostic quality of the lymphoscintigraphic image and adherence to interpretive criteria already established therefore preclude the routine use of 99Tc(m) stannous phytate for interstitial lymphoscintigraphy.     

Technetium Tc 99m plasmin in the diagnosis of inflammatory disease

The localization characteristics of technetium Tc 99m plasmin were studied in experimental animals to investigate the use of^99mTc-plasmin for imaging inflammatory processes. At various times after abscess induction using turpentine in rats, the in vivo distribution properties of^99mTc-plasmin, gallium citrate Ga 67,¹²⁵I-fibrinogen, and^99mTc-human serum albumin (HSA) were studied by gamma-camera imaging. The in vivo binding of each radiopharmaceutical was also tested in rat and human plasma clots. Region-of-interest analyses of gamma-camera images showed relatively poor^99mTc-plasmin localization at sites of abscess formation. The ratio of abscess-to-control activity of this radiopharmaceutical did not exceed that of⁶⁷Ga,¹²⁵I-fibrinogen, or^99mTc-HSA. In vitro assays of each of the radiopharmaceuticals in plasma clots showed^99mTc-phasmin and¹²⁵I-fibrinogen to have the best localization characteristics.     

Technetium Tc 99m plasmin in the diagnosis of inflammatory disease

The localization characteristics of technetium Tc 99m plasmin were studied in experimental animals to investigate the use of 99mTc-plasmin for imaging inflammatory processes. At various times after abscess induction using turpentine in rats, the in vivo distribution properties of 99mTc-plasmin, gallium citrate Ga 67, 125I-fibrinogen, and 99mTc-human serum albumin (HSA) were studied by gamma-camera imaging. The in vivo binding of each radiopharmaceutical was also tested in rat and human plasma clots. Region-of-interest analyses of gamma-camera images showed relatively poor 99mTc-plasmin localization at sites of abscess formation. The ratio of abscess-to-control activity of this radiopharmaceutical did not exceed that of 67Ga, 125I-fibrinogen, or 99mTc-HSA. In vitro assays of each of the radiopharmaceuticals in plasma clots showed 99mTc-plasmin and 125I-fibrinogen to have the best localization characteristics.