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PubMed2005

Intraorgan biodistribution and dosimetry of 153Sm-ethylenediaminetetramethylene phosphonate in juvenile rabbit tibia: implications for targeted radiotherapy of osteosarcoma.

UNLABELLED: Targeted radiotherapy using 153Sm-ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) is currently under investigation for treatment of primary osteosarcoma. Human osteosarcoma most frequently occurs in skeletally immature individuals, and previous studies in a juvenile rabbit model demonstrated that clinically significant damage to developing physeal cartilage might occur as a result of systemic 153Sm-EDTMP therapy. The aim of this study was to determine the distribution of 153Sm-EDTMP within the tibias of juvenile rabbits and estimate the radiation-absorbed doses delivered to the physeal cartilage. METHODS: Eight-week-old New Zealand White rabbits were injected intravenously with 7.57 kBq (280 microCi) of 153Sm-EDTMP. At 21 h after injection, the biodistribution of 153Sm in the epiphysis, metaphysis, diaphysis, and red marrow of the tibia was obtained. Two-dimensional digital autoradiography was performed on 2-mm sections of tibias for qualitative comparison with the biodistribution data. Self-tissue and cross-tissue absorbed doses were calculated using absorbed fractions generated by the Monte Carlo particle transport code MCNP-4C. RESULTS: The highest uptakes (percentage injected dose per gram [%ID/g] of tissue) of 153Sm, 1.99-2.56 %ID/g, were found in the proximal and distal metaphyses, 70%-73% of which localized within 3 mm of the physeal cartilage. The second highest tissues of uptake were the proximal and distal epiphyses, at 0.33-0.62%ID/g. Digital autoradiography imaging confirmed that the majority of 153Sm deposited in the tibia localized to these tissues. Radiation-absorbed doses to the proximal and distal metaphyses were 183 and 130 mGy/MBq, respectively, and those to the proximal and distal epiphyses were 141 and 43.4 mGy/MBq, respectively. These tissues represented the only source compartments contributing to the physeal cartilage doses of 50.0 mGy/MBq for the proximal physis and 39.2 mGy/MBq for the distal physis. CONCLUSION: The 153Sm absorbed doses to the physeal cartilage were consistent with values that can cause dose-limiting damage to rapidly proliferating and differentiating chondrocytes. The pronounced uptake in the juvenile epiphysis indicates that the proliferating zone of the physis can be irradiated from multiple areas, which could increase the expression and degree of radiation damage. Further investigation of the effects of 153Sm-EDTMP on immature physeal cartilage is warranted to develop optimized treatment regimens.

Analgesics, Non-Narcotic↗
PubMed1990

[Kinetics and clinical application of 99mTc-technegas].

Biological characteristics and clinical utilization of 99mTc-technegas were evaluated in three normal volunteers and 10 patients with various pulmonary diseases. 99mTc-pertechnetate (296 MBq (8 mCi] was injected in the crusible of 99mTc-technegas generator, and about 37 MBq (1 mCi) of 99mTc-technegas was inhaled in the lung by three times of deep inspiration. Blood activity was appeared immediately after inhalation of 99mTc-technegas and it was 0.2% of the inhaled dose/liter of blood after 2 hours. Urine activity was also increased after inhalation and cumulative dose was 4.96% of the inhaled dose after 24 hours. The tracer dose to distribution to the lung was about 95% of the total dose in whole body. Biological half time of 99mTc-technegas in the lung was 135 hours and pulmonary image was stable even after 24 hours. Radiation dose to the lung was 0.004 Gy/37 MBq (1 mCi). In patients with pulmonary disease, distribution of 99mTc-technegas was similar to that of 81mKr gas, although defect on 99mTc-technegas image was larger in severe obstructive disease. 99mTc-technegas study was superior over 133Xe gas study to identify the areas of ventilation abnormality more clearly, although quantitative evaluation was difficult in 99mTc-technegas study. On comparative study with 99mTc-aerosol, 99mTc-technegas distributed in more peripheral sites and both methods were cooperative for evaluation of ventilatory disturbance. These results suggest that 99mTc-technegas inhalation study is safe and useful method for ventilation study.

Administration, Inhalation↗
PubMed1990

[Side effects of extracorporeal shock-wave exposure on the kidney in the dogs].

The effects of extracorporeal shock-wave (SW) exposure on the kidney were investigated in dogs using a Dornier kidney lithotriptor HM3. The SW was generated by spark discharge at 20 KV and was focused on the lower part of either kidney. Before and after the exposure of 500 and 1000 shots of SW, the renal blood flow of the affected and contralateral kidney was measured by the microsphere method. The blood flow of the affected kidney decreased, but was comparable to that of the contralateral kidney immediately after the 1000 shots of SW. Renal scintigraphy using 99mTc-DTPA was performed before the exposure of SW, and 30 minutes, 1 week, 2 weeks and 4 weeks after the exposure. The renograms were evaluated by the following parameters: Tmax (time required to reach maximum radioactivity), RAmax ratio (maximum radioactivity of the affected kidney/that of the contralateral kidney) and T1/2 (the half-life of elimination). Tmax was significantly prolonged for the affected kidney 30 minutes after the exposure, while that for the contralateral kidney was shortened. The RAmax ratio was decreased 1 week after the exposure. T1/2 was significantly prolonged 30 minutes after the exposure, which was observed till 2 weeks later. The scintigraphy also showed a slight enlargement of affected site. The histological study showed a hemorrhage in the peritubular space, indicating rupture of the peritubular capillaries. In conclusion, the main effect of SW exposure on the kidney was the rupture of the peritubular capillaries, resulting in temporary and reversible deterioration of renal function.

Animals↗
PubMed1991

Pharmacological stress with adenosine for myocardial perfusion imaging.

Adenosine is a ubiquitous purine base that has many physiological actions in the body, including arterial vasodilation in all vascular beds, with the exception of the kidneys. Myocardial ischemia causes an immediate breakdown of adenosine triphosphate and generates adenosine, thereby producing coronary vasodilation and restoring flow. Adenosine produces vasodilation by interacting with the adenosine receptors in the cell wall. Exogenously administered adenosine has a very short half-life (less than 10 seconds) and produces maximal or near-maximal coronary vasodilation in a dose-dependent fashion. The underlying mechanism for production of myocardial perfusion defects by adenosine thallium 201 scintigraphy is a greater coronary flow increase in the normal arteries and a lesser increase in the stenotic arteries. The ultra-short half-life of adenosine requires a continuous intravenous infusion for its use. Adenosine is often administered as a continuous intravenous infusion at a dose of 140 micrograms/kg per minute for 6 minutes, with the thallium injection given midway through the infusion. The safety of this regimen has been demonstrated in several thousand patients around the country. Side effects, due in great part to the potent vasodilatory effect of the drug, occur in most patients during adenosine infusion. Chest pain also occurs often and in some cases may be due to a true coronary steal phenomenon. First-degree atrioventricular (AV) block occurs in approximately 10% and second- or third-degree AV block in approximately 4% of patients due to the inhibitory effect of adenosine on the AV node conduction. The side effects are very short-lived and typically disappear within 1 or 2 minutes after discontinuing the adenosine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed2002

Exercise training following myocardial infarction improves myocardial perfusion assessed by thallium-201 scintigraphy.

AIM: We assessed the effects of a 6-week exercise programme on the thallium-201 myocardial perfusion characteristics of patients following myocardial infarction. METHODS: Twenty-five patients presenting with a first acute myocardial infarction were randomised into two groups: (i) those undergoing a supervised exercise training programme over 6 weeks (n=15) and (ii) a control group who did not attend the exercise programme (n=10). All underwent three sequential stress thallium myocardial perfusion scans at 10 days, 6 weeks and 3 months after infarction. The stress conditions were identical on each occasion. The images were analysed using a polar plot with a computer assisted algorithm comparing stress and redistribution data. Values for extent, severity and percentage redistribution of the thallium images were generated. RESULTS: A total of 29 perfusion defects were identified, 18 in the exercise group and 11 in the control group. Over 3 months in the exercise group the mean extent of the stress image defect fell from 109+/-64 to 95+/-51 pixels (P<0.05) while in the control group there was an increase from 133+/-57 to 144+/-57 pixels (P=ns). Stress defect severity fell in the exercise group from 581+/-417 to 494+/-346 S.D. (P<0.05) but increased in the control group from 765+/-494 to 877+/-543 S.D. (P=ns). On redistribution imaging in the exercise group a significant decrease was observed in both extent (94+/-56 to 76+/-43 pixels (P<0.05)) and severity (541+/-387 to 438+/-291 S.D. (P<0.05)) of the defects. However in the control group no significant change was observed for extent (125+/-54 to 125+/-52 pixels) or severity (745+/-485 to 820+/-503 S.D.) of the redistribution defects (P=ns). Reversibility of the defects increased slightly in both the exercise group (from 14.6+/-17 to 17.5+/-20%) and the control group (5.2+/-5 to 9.6+10%) (P=ns). CONCLUSION: Following myocardial infarction a 6-week exercise programme improves myocardial perfusion characteristics. An exercise programme should be integrated into cardiac rehabilitation protocols for patients after infarction.

Aged↗
PubMed2005

Language laterality determined by MEG mapping with MR-FOCUSS.

Magnetoencephalography recordings were made on 27 patients with localization related epilepsy during two different language tasks involving semantic and phonological processing (verb generation and picture naming). These patients underwent the semi-invasive intracarotid amobarbital procedure (IAP), also referred to as the Wada test, to determine the language-dominant hemisphere. Magnetoencephalography (MEG) data were analyzed by MR-FOCUSS, a current density imaging technique. A laterality index (LI) was calculated from this solution to determine which hemisphere had more neural activation during these language tasks. The LIs for three separate latencies, within each language task, were calculated to determine the latency that correlated best with each patient's IAP result. The LI for all language processing was calculated for the interval 150-550 ms, the second LI was calculated for the interval 230-290 ms (Wernicke's activation), and the third LI was calculated for the interval 396-460 ms (Broca's activation). In 23 of 24 epilepsy patients with a successful IAP, the LIs for Broca's activation, during the picture naming task, were in agreement with the results of the IAP (96% agreement). One of three patients who had an undetermined or bilateral IAP had an LI calculated for Broca's activation (396-460 ms) that agreed with intracranial mapping and clinical testing. These results indicate an 89% agreement rate (24 of 27) for magnetoencephalographic LI determination of the hemisphere of language dominance.

Adolescent↗
PubMed1995

Effect of radioiodine therapy on pulmonary alveolar-capillary membrane integrity.

UNLABELLED: The effects of large doses of radioiodine on the pulmonary alveolar-capillary membrane using 99mTc-DTPA clearance as an index of pulmonary damage in subjects with pulmonary metastases of differentiated thyroid carcinoma were studied. METHODS: Technetium-99m-DTPA radioaerosols were generated by a dry aerosol generator. Data were acquired and analyzed for clearance half-time from the lungs with a scintillation camera. The study was carried out on 35 thyroid cancer patients with pulmonary metastases and on 32 patients without metastases; the results were compared to those of a control group comprising 52 subjects. The radiation dose delivered to the lungs from the therapeutic dose was calculated using MIRD methodology. RESULTS: Cumulative radioiodine doses varied from 5.9 to 44.2 GBq (158-1194 mCi). The half-time clearance of 99mTc-DTPA was comparable in both patient groups and was not related to the total administered radioiodine dosage or to the radiation dose delivered to the lungs. No changes were observed for periods up to 5 yr after receiving the last radioiodine dosage. Seven patients followed at regular intervals from 6 mo to 2 yr did not show abnormal 99mTc-DTPA clearance values. One patient did show low 99mTc-DTPA clearance half-time values, which were symptomatic radiation pneumonitis. She had received a total dose of 34 GBq (922 mCi) over a 4-yr period. CONCLUSION: The incidence of pulmonary damage resulting from radioiodine therapy for lung metastases of differentiated thyroid cancer is negligible, as evidenced by the normal pulmonary clearance half-time of 99mTc-DTPA aerosols.

Adult↗
PubMed1996

Lag phase quantification for solid gastric emptying studies.

UNLABELLED: This study compared the different calculation methods of the solid gastric emptying lag phase and evaluated the effect of the temporal sampling interval on the calculated value using the modified power exponential (MPE) method. METHODS: Twenty normal control subjects and 42 patients had anterior and posterior image acquisition on a multihead gamma camera, one frame per minute x 90. ROIs were selected for the stomach, gastric antrum and small bowel. Time-activity curves (TACs) were generated for anterior, posterior and geometric mean data. The lag phase was calculated using various methods such as transition point, starting index, first appearance of bowel activity (FABA), MPE and antral peak filling time. To determine the importance of the temporal sampling rate on the calculation of the lag phase by the MPE, intervals between 1 and 20 min were analyzed. RESULTS: The transition point, starting index and FABA correlated extremely high (r = > or = 0.92) in normal control subjects and patients. Normal lag phase values were mean 22-24 +/- 10 min for transition point, starting index and FABA compared with 47 +/- 18 min for the MPE method (p < 0.0001). The MPE correlated poorly with the other method (r = 0.74). Antral peak filling time correlated poorly (r = 0.47) with transition point, starting index and FABA, but somewhat better with the MPE (r = 0.70). Comparing 15-min versus 1-min sampling intervals using the MPE, 35% of subjects had values that differed by > or = 7.5 min and 10% had values differing by > or = 15 min. CONCLUSION: The lag phase calculated by the MPE correlated poorly with other methods, and its accuracy was limited by the rate of the temporal sampling. The transition point, starting index and FABA all highly correlated with each other; the latter is a particularly reliable physiological indicator and is easily quantified using a small-bowel TAC.

Adolescent↗
PubMed2004

Diagnosing infection in the failed joint replacement: a comparison of coincidence detection 18F-FDG and 111In-labeled leukocyte/99mTc-sulfur colloid marrow imaging.

UNLABELLED: The objectives of this study were to investigate (18)F-FDG imaging, using a coincidence detection system, for diagnosing prosthetic joint infection and to compare it with combined (111)In-labeled leukocyte/(99m)Tc-sulfur colloid marrow imaging in patients with failed lower extremity joint replacements. METHODS: Fifty-nine patients--with painful, failed, lower extremity joint prostheses, 40 hip and 19 knee--who underwent (18)F-FDG, labeled leukocyte, and bone marrow imaging, and had histopathologic and microbiologic confirmation of the final diagnosis, formed the basis of this investigation. (18)F-FDG images were interpreted as positive for infection using 4 different criteria: criterion 1: any periprosthetic activity, regardless of location or intensity; criterion 2: periprosthetic activity on the (18)F-FDG image, without corresponding activity on the marrow image; criterion 3: only bone-prosthesis interface activity, regardless of intensity; criterion 4: semiquantitative analysis--a lesion-to-background ratio was generated, and the cutoff value yielding the highest accuracy for determining the presence of infection was determined. Labeled leukocyte/marrow images were interpreted as positive for infection when periprosthetic activity was present on the labeled leukocyte image without corresponding activity on the marrow image. RESULTS: Twenty-five (42%) prostheses, 14 hip and 11 knee, were infected. The sensitivity, specificity, and accuracy of (18)F-FDG, by criterion, were as follows: criterion 1: 100%, 9%, 47%; criterion 2: 96%, 35%, 61%; criterion 3: 52%, 44%, 47%; criterion 4: 36%, 97%, 71%. The sensitivity, specificity, and accuracy of labeled leukocyte/marrow imaging were 100%, 91%, and 95%, respectively. WBC/marrow imaging, which was more accurate than any of the (18)F-FDG criteria for all prostheses, as well as for hips and knees separately, was significantly more sensitive than criterion 3 (P < 0.001) and criterion 4 (P < 0.001) and was significantly more specific than criterion 1 (P < 0.001), criterion 2 (P < 0.001), and criterion 3 (P < 0.001). CONCLUSION: Regardless of how the images are interpreted, coincidence detection-based (18)F-FDG imaging is less accurate than, and cannot replace, labeled leukocyte/marrow imaging for diagnosing infection of the failed prosthetic joint.

Adult↗
PubMed1998

Biodistribution and dosimetry of iodine-123-labelled Z-MIVE: an oestrogen receptor radioligand for breast cancer imaging.

This study reports on the distribution and radiation dosimetry of iodine-123-labelled cis-11beta-methoxy-17alpha-iodovinyloestradiol (Z-[123I]MIVE), a promising radioligand for imaging of oestrogen receptors (ERs) in human breast cancer. Whole-body scans were performed up to 24 h after intravenous injection of 138-193 MBq Z-[123I]MIVE in five healthy female volunteers, four with and one without thyroid blockade. Blood samples were taken at various times up to 24 h after injection. Urine was collected up to 24 h after injection in order to calculate renal clearance and to aid in the interpretation of whole-body clearance, including faecal excretion. Time-activity curves were generated for the thyroid, heart, brain, breasts and liver, by fitting the organ-specific geometric mean counts, obtained from regions of interest, to a multicompartmental model. The MIRD formulation, using 11 source organs, was applied to calculate the absorbed radiation doses for various organs upon administration of Z-[123I]MIVE. The images showed rapid hepatobiliary excretion which resulted in good imaging conditions for the thoracic region. Imaging of the abdominal region was impeded due to extensive bowel activity. Diffuse uptake and retention of activity was seen in breast tissue, the breast-to-non-specific uptake ratio increasing over time. Z-[123I]MIVE was cleared by both the kidneys and the gastrointestinal tract. At 50 h p.i. the mean excretion in urine was predicted to be 58%+/-14% (SD) and that in faeces 31%+/-19%. If the thyroid was not blocked, it was the most critical organ (0.33 mGy/MBq). In general, the excretory organs received the highest absorbed doses, i.e. the lower and upper large intestinal walls (0.11 and 0.098 mGy/MBq, respectively), the urinary bladder wall (0.090 mGy/MBq), the gallbladder wall (0.087 mGy/MBq) and the small intestine (0.043 mGy/MBq). The average effective dose equivalent of Z-[123I]MIVE was estimated to be 0.033 mSv/MBq. The amount of Z-[123I]MIVE required for adequate breast cancer ER imaging results in an acceptable effective dose equivalent to the patient.

Adult↗
PubMed2003

Preliminary results of a functional MRI study of brain activation patterns in stuttering and nonstuttering speakers during a lexical access task.

UNLABELLED: An fMRI study examining lexical access and lexical generation in nine non-stuttering and seven stuttering speakers is presented. Lexical access was examined during a word description task that was presented auditorily while subjects "silently" thought of the target words. Participants alternated between four 30-s rest blocks and four 30-s "active" blocks. Activation patterns were assessed utilizing a standard subtraction paradigm, where the activation during the rest blocks was subtracted from the activation during the active blocks. High levels of variability characterized activation patterns within both speaker groups. Group comparisons using random effects statistical analyses did not identify significant differences between the groups when corrected for multiple comparisons. Analyses were subsequently conducted by comparing the trends in the group activation patterns between the speaker groups using fixed (corrected) and random effects (uncorrected) analyses. Non-stuttering control speakers activated primarily left hemisphere cortical speech and language areas while the stuttering speakers appeared to produce more bilateral activation. Discussion of these results focuses on the specific within- and between-hemispheric activation patterns and possible interpretations of these patterns. EDUCATIONAL OBJECTIVES: The reader will learn about: (1) issues related to interpreting brain activation findings in stuttering speakers; (2) the role and neurological substrates of lexical access during speech production in non-stuttering and stuttering speakers; (3) the basics of functional MRI; and (4) the brain activation areas involved during a silent lexical retrieval task in non-stuttering and stuttering speakers.

Adult↗
PubMed1998

Bystander effect-mediated therapy of experimental brain tumor by genetically engineered tumor cells.

Transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene, followed by administration of ganciclovir (GCV), generates the "bystander effect," in which HSV-tk-negative wild-type cells, as well as HSV-tk-expressing cells, are killed by GCV. To eradicate an intracranial tumor by this bystander effect, we injected the tumor cells transduced with the HSV-tk gene (TK cells) in the vicinity of the preimplanted wild-type tumor and then administered GCV. Wild-type 9L-gliosarcoma cells (1 x 10[5]) were implanted into the brain of syngeneic Fisher rats. On the next day, rats were injected with TK cells (1 x 10(5) or 3 x 10[5]) or medium alone at the same brain coordinate and then treated with GCV or saline. Administration of GCV significantly prolonged the survival of the rats injected with TK cells compared with that injected with medium alone (p < 0.01). Reduction in tumor size and retardation of tumor growth were observed by serial magnetic resonance imaging in the rats that received the combination of TK cells and GCV. The results show that the bystander effect is also achieved in vivo even when TK cells and wild-type cells are not simultaneously implanted. This treatment modality circumvents potential risks accompanied with in vivo gene transfer. Because there remained substantially no HSV-tk-positive cells in the recurrent tumors, this modality offers a "safe" therapeutic strategy against human malignant gliomas.

Animals↗
PubMed2006

Tissue-targeting lead generation and optimization from random and directed screening of technetium-99m labeled tripeptide complex libraries in vivo.

BACKGROUND: Screening libraries against a molecular target in vitro are idealized models that cannot reflect the real state in vivo where biomolecules coexist and interact. C-terminal amide tripeptides labelled with Technetium-99m can provide a unique noninvasive approach to trace a large number of compounds in vivo. METHODS: The C-terminal amide tripeptide libraries were synthesized on Rink Amide-MBHA resin using iterative and pooling protocol. Technetium (V) oxo core [TcO(3+)] was bound to each tripeptide via 4 deprotonated nitrogen atoms to form a library of 8000 (99m)Tc tripeptoid complexes. The radiocombinatorial screening (RCS) in vivo was carried out on SD rats and A549 tumour bearing mice. RESULTS: Signals of tissue distribution and metabolism of libraries were recorded by counting or imaging and tissue targeting leads identified by both random and directed RCS. Among them, (99m)Tc RPA, (99m)Tc VIG and (99m)Tc RES had specific tissue targeting in kidney, liver and tumour respectively. The percent injected dose per gram tissue of (99m)Tc labelled leads in their target tissue was highly structure dependent. Because the nontarget tissue binding and the metabolism of (99m)Tc tripeptoid sublibraries were simultaneously monitored successfully by RCS, the interference of background activity was limited to the lowest level. Optimization of renal function agent from the labelled libraries was carried out by directed screening. (99m)Tc DSG was finally identified the most promising agent for renal function studies. CONCLUSIONS: RCS in vivo is a powerful tool for the discovery of tissue targeting drugs. The potential screening bias is probably the major limitation of labelled libraries.

Animals↗
PubMed1995

Infarct size after acute myocardial infarction measured by quantitative tomographic 99mTc sestamibi imaging predicts subsequent mortality.

BACKGROUND: 99mTc sestamibi is a recently developed radioisotope that has been used to measure myocardium at risk and infarct size. The relation between these measurements and subsequent patient outcome has not yet been demonstrated. METHODS AND RESULTS: Two hundred seventy-four consecutive patients with acute myocardial infarction underwent tomographic 99mTc sestamibi imaging on arrival at the hospital (to measure myocardium at risk before reperfusion therapy) and at hospital discharge (to measure the amount of salvaged myocardium and final infarct size). Defect size on the sestamibi images was quantified using a threshold value of 60% of peak counts from the circumferential count profile curves generated for five representative slices of the left ventricle. Patients were followed after hospital discharge to evaluate the association between final infarct size and subsequent mortality. The median defect size measured was 27% of the left ventricle at presentation to the hospital (range, 0% to 77%) and was 12% of the left ventricle at hospital discharge (range, 0% to 68%). Almost one half of the patients had a final infarct size of < or = 10%. The median amount of myocardium salvaged was 9% (range, -31% to 75%). During a median duration of follow-up of 12 months, there were 10 deaths (7 cardiac and 3 noncardiac) and 1 resuscitated out-of-hospital cardiac arrest. There was a significant association between infarct size and overall mortality (chi 2 = 8.66, P = .003) and cardiac mortality (chi 2 = 11.89, P < .001). Two-year mortality was 7% for patients whose infarct size was > or = 12% versus 0% for patients whose infarct size was < 12%. There also was a significant association between myocardium at risk and cardiac mortality (chi 2 = 6.87, P = .009). There was no association between myocardium at risk and overall mortality or between amount of myocardium salvaged and either overall mortality or cardiac mortality. CONCLUSIONS: Larger infarct size measured by 99mTc sestamibi imaging after acute myocardial infarction is associated with increased mortality risk during short-term follow-up.

Aged↗
PubMed2000

Recombinant versus natural human 111In-beta2-microglobulin for scintigraphic detection of Abeta2m amyloid in dialysis patients.

BACKGROUND: We previously introduced scintigraphy with 131I-labeled beta2-microglobulin (beta2m), purified from uremic hemofiltrate, that is, "natural" beta2m, to specifically detect beta2m-associated amyloidosis (Abeta2m) in hemodialysis (HD) patients. METHODS: To improve the safety and resolution of the scan, we covalently bound the chelator diethylenetriaminepentaacetic acid to natural beta2m to allow radiolabeling with 111In. In a second step, we generated and evaluated the usage of recombinant human beta2m (rhbeta2m) for scintigraphy. RESULTS: Using natural 111In-labeled beta2m, eight patients on HD for 0 to 17 years, without evidence of Abeta2m, were scanned. Whole-body scintigraphy at 48 to 72 hours postinjection revealed no significant tracer accumulation over joint regions. In contrast, nine patients on HD for 10 to 21 years with clinical, radiological, or histologic (N = 4) evidence of Abeta2m showed selective tracer uptake over various joint regions. Tracer accumulation in visceral organs, which could not be related to tracer elimination or metabolism, was not detected. Compared with the previous 131I beta2m scan, scintigraphy with 111In-labeled beta2m offered highly improved image contrast, increased sensitivity, and a 50 to 70% reduction of the radiation exposure. Scanning with 111In-labeled recombinant human beta2m was performed in six patients: No significant tracer accumulation was observed over joint regions in two patients on short-term HD without evidence of Abeta2m; in contrast, local tracer accumulations similar to those observed with natural beta2m could be demonstrated in four long-term (10 to 27 years) HD patients with clinical, radiological, and histologic (N = 1) evidence of Abeta2m. CONCLUSION: Scintigraphy for Abeta2m with 111In-labeled rhbeta2m provides a homogenous and safe recombinant protein source and leads to enhanced sensitivity and lower radiation exposure.

Adult↗
PubMed1989

Simultaneous measurement of lung clearance rates for Tc- and In-DTPA in normal and damaged lungs.

We investigated the relative clearance rates for 99mTc-labeled diethylenetriamine-pentaacetate (Tc-DTPA) and 113mIn-labeled DTPA (In-DTPA) when they were inhaled and deposited together within the lungs of same animal. Submicronic aerosols containing Tc-DTPA and In-DTPA were simultaneously generated by different nebulizers and collected within the same anesthetic bag. The combined aerosols were insufflated into piglets. Clearances for both compounds were measured simultaneously in normal lungs and when the lungs were damaged by intravenous oleic acid or by a presumed oxidant agent, intravenous or intratracheal phorbol myristate acetate (PMA). A medium-energy collimator and a computer-assisted gamma camera were used to calculate clearances. Correction was made for downscatter from the In photopeak into the Tc window. Marked lung injury occurred as evidenced by increases in lung water content and decreases in arterial PO2. The clearance of In-DTPA was slightly but significantly slower than for Tc-DTPA in each group of animals. The correlation (r = 0.93) between clearances for Tc-DTPA and In-DTPA was good, even though in vitro studies demonstrated that Tc-DTPA, but not In-DTPA, slowly dissociated at room and body temperatures. Oleic acid increased, but surprisingly, PMA had no effect on clearance rates for both In-DTPA and Tc-DTPA. We recommend continued use of Tc-DTPA for these measurements in view of its lower cost, requirement for only low-energy collimation, better imaging characteristics, and widespread availability. The overlap between control and injured lungs and the lack of increased clearance rates after PMA suggest this technique does not always detect acute lung injury.

Aerosols↗
PubMed2004

[Lower limb hemodynamic evaluation in patients with diabetic foot using 99mTc-methylene diphosphonate three-phase bone scintigraphy].

OBJECTIVE: To evaluate the efficacy of (99m)Tc-methylene diphosphonate (MDP) bone scintigraphy in diagnosis of diabetic foot. METHODS: (99m)Tc-MDP three-phase bone imaging was performed in 56 patients with diabetic foot and 36 non-diabetic control subjects, each foot was analyzed independently. The radioactive concentration per pixel hence the foot to tibia ratio (R(m/t)) was calculated and the time-radioactivity curve of each region of interest generated. From the curve the perfusion time (Tp) was read and the velocity of uptake rate (V) of the foot calculated. The indices such as R(m/t), Tp and V were compared between the two groups by t test, and the diagnostic indices such as sensitivity, specificity, accuracy, positive prediction value and negative predictive value were compared using u test. RESULTS: In the control group, the Tp, V and R(m/t) were 32.9+/-9.8 s, 2.301+/-0.754 counts/s and 0.85+/-0.29, respectively, which were 36.1+/-15.3 s, 1.574+/-0.341 counts/s and 0.72+/-0.31 respectively in the diabetic group. Tp was not significantly different (t=1.693, P>0.05) between the two groups, as was V (t=8.396, P<0.001) and R(m/t)(t=2.759, P<0.01). When V was used as the index, the sensitivity, specificity, and accuracy were 80.2%, 82.8% and 81.5%, respectively, and those for R(m/t) were 65.2%, 68.8% and 67.3%, respectively. By comparison, the sensitivity (u=2.3274, P<0.05) and specificity (u=2.4068, P<0.05) of V were significantly higher than those of R(m/t). CONCLUSIONS: (99m)Tc-MDP three-phase bone imaging can identify decreased uptake rate and R(m/t) in the diabetic foot, and the former index can be more sensitive and specific to define the hemodynamics in the diabetic foot. This technique may detect hemodynamic abnormity in early stage and greatly assist the diagnoses and treatment.

Adult↗
PubMed1984

A new approach to quantitation of exercise thallium-201 scintigraphy before and after an intervention: application to define the impact of coronary angioplasty on regional myocardial perfusion.

We have developed a new computer method designed to quantitate regional myocardial thallium-201 (TI-201) initial distribution, redistribution, and clearance rate. In addition, this computer method permits the generation of functional images to compare two thallium images in the same projection to one another. These functional images can be used to demonstrate the extent of redistribution and the extent of change in regional perfusion before and after an intervention. To validate and apply this new computer technique, exercise TI-201 myocardial images obtained before and 1 week after percutaneous transluminal coronary angioplasty (PTCA) were analyzed in 20 patients with isolated left anterior descending coronary artery disease. Significant improvement in initial TI-201 activity, expressed as a percentage of maximal myocardial activity, was present in the anterior (71.9 +/- 12.0 to 84.1 +/- 11.5%, p less than 0.001) and septal (66.7 +/- 15.4 to 75.2 +/- 11.0%, p less than 0.05) regions of the left ventricle 1 week after PTCA. This increase in relative anterior wall TI-201 uptake was associated with a significant reduction in the amount of TI-201 redistribution between initial and delayed postexercise images (14.7 +/- 14.6 to 3.0 +/- 13.2%, p less than 0.05) as well as an increase in TI-201 clearance rate (t 1/2 from 8.8 +/- 4.4 to 4.3 +/- 2.5 hours, p less than 0.001). Quantitative analysis of TI-201 scans demonstrated improvement in 14 of 20 patients following PTCA. Computer-derived functional difference images depicted diminution in the extent of ischemia as manifested by redistribution of TI-201.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗