Preliminary quantitative evaluation of radiation-induced DNA damage in peripheral blood lymphocytes after cardiac dual-isotope imaging.

DNA double-strand breaks (DSBs) of peripheral blood lymphocyte were prospectively assessed in 9 patients who were injected with 201Tl-chloride and 123I-beta-methyl-p-iodophenyl-pentadecanoic acid in dual-isotope imaging. Phosphorylated H2AX (γH2AX) was used as a biomarker for detecting DSBs, and the mean number of γH2AX foci per cell was measured microscopically. Mean γH2AX foci before administration of radiopharmaceuticals and at 3, 6, and 24 h following administration were 0.22 ±â€¯0.34, 0.10 ±â€¯0.14, 0.59 ±â€¯0.46, and 0.52 ±â€¯0.40, respectively (p = n.s. for all combinations).

The prognostic value of ultra low-dose thallium myocardial perfusion protocol using CZT SPECT.

The purpose of this study was to assess the prognostic value of ultra-low dose thallium myocardial perfusion imaging. Three hundred and sixty-six patients (245 men) underwent ultra-low dose stress-redistribution imaging on CZT SPECT camera GE Discovery NM 530c. The stress test was performed by bicycle ergometry or regadenoson injection. The activity of 0.5 MBq (0.014 mCi) Tl-201 chloride per kilogram of body weight was administered. The stress images were acquired immediately and redistribution images were taken after 3 h. Patient follow-up was focused on combined end-point (death, myocardial infarction, unstable angina, revascularization and hospitalization for heart failure). Data analysis was performed from hospital database, with a mean period 23 months. Patients with revascularization within 1 month after SPECT was excluded as revascularization for diagnosis. Ischaemia on SPECT was found in 72 patients, 294 patients were without ischaemia. In patients with ischaemia there were 21 (29.2%) subjects with cardiac events, and 23 (7.9%) in patients without ischaemia (HR 4.15, 95% CI 2.30-7.51, p < 0.0001). Ultra-low dose thallium perfusion imaging using CZT camera provides very good prognostic results in assessment of myocardial ischaemia.

Evaluation of a novel decorporation approach to prevent radioactivity uptake by using acidosis in experimental animals.

With an aim to devise a prophylactic and/or therapeutic approach for preventing internalization of radiothallium (201Tl), and more importantly by implication, its chemical analogue radiocesium (137Cs) during any nuclear emergency, different ex vivo and in vivo animal models were created to determine the role ofpH in absorption of 201Tl across jejunum/muscle tissue and whole body retention of 201Tl respectively. Movement of Tl+ under simulated pH conditions proved that pH had direct influence on its absorption. Oral intake of acidified water or parenteral administration of lactic acid was able to reduce the body burden of 201Tl by up to 12 and 50% respectively. The results indicate that acidification of gut, within physiological range may be used as an option for decorporation/inhibition of incorporation of radiothallium and radiocesium, particularly in cases of mass casualty.

Adenosine stress thallium-201 myocardial perfusion imaging for detecting coronary artery disease at an early stage.

The aims of this study were to evaluate the diagnostic value of adenosine thallium-201 myocardial perfusion imaging and to compare it with exercise stress thallium-201 myocardial perfusion imaging for detecting coronary artery disease (CAD) at an early stage. Forty-one patients suspected with CAD were randomly divided into two groups. In Group 1 (n=21) adenosine stress was undertaken; the exercise stress myocardial perfusion imaging was performed in Group 2 (n=20). Coronary angiography (CAG) was performed in each patient within 2 weeks before or after single photon emission computed tomography (SPECT). Adenosine stress group vs. exercise stress group, the sensitivity was 92.86% vs. 100.0%, specificity 57.14% vs. 60.0%, positive predictive value 81.25% vs. 71.43%, negative predictive value 80.0% vs. 100.0%, accuracy 80.95% vs. 80.0% respectively. Detection rates of vessels of coronary artery lesions were 66.67% in Group 1 and 72.22% in Group 2 (P> 0.05). The side effects were mild and transient. Our results demonstrated that adenosine stress myocardial perfusion imaging is a safe and reliable diagnostic method for an early stage of CAD. As a comparative sensitivity and accuracy with exercise stress thallium-201 myocardial perfusion imaging, adenosine stress testing may provide a feasible alternative pharmacological stress method in myocardial SPECT for detection of CAD.

Estimation of potential excess cancer incidence in pediatric 201Tl imaging.

OBJECTIVE: Little information is available regarding doses of ionizing radiation from medical imaging in the growing population of children undergoing therapy for cancer who are at risk of developing second cancers. The purpose of our study was to estimate the potential excess lifetime cancer incidence and mortality associated with thallium bone imaging in pediatric patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of pediatric patients treated between August 1991 and December 2003 for newly diagnosed osteosarcoma who underwent 201Tl imaging as part of the treatment protocol. According to age at diagnosis and doses of 201Tl, we estimated the excess cancer incidence and cancer mortality for boys and girls at 5 and 15 years old. RESULTS: The study cohort consisted of 73 patients, 32 males (median age at diagnosis, 14.8 years; age range, 8.1-20.1 years) and 41 females (median age at diagnosis, 13.3 years; age range, 6.0-20.7 years). Patients underwent a total of three 201Tl studies with a median dose of 4.4 mCi (162.8 MBq) (range, 2.2-8.4 mCi [81.4-310.8 MBq]) per study. Total median cumulative patient radiation dose for 201Tl studies was 18.6 rem (186 mSv) (range, 8.4-44.2 rem [84-442 mSv]) for males and 21.5 rem (215 mSv) (range, 7.0-43.8 rem [70-438 mSv]) for females. Estimated excess cancer incidence was 6.0 per 100 (male) and 13.0 per 100 (female) if exposed by 5 years of age; 2.0 per 100 (male) and 3.1 per 100 (female) by 15 years of age. Estimated excess cancer mortality was 3.0 per 100 for males and 5.2 per 100 for females at 5 years of age; 1.0 per 100 (male) and 1.4 per 100 (female) exposed at 15 years of age. CONCLUSION: Further reduction of doses in younger patients is needed to consider 201Tl a viable option for imaging osteosarcoma.

Safety of and tolerance to adenosine infusion for myocardial perfusion single-photon emission computed tomography in a Japanese population.

BACKGROUND: Adenosine has been available for use in myocardial perfusion single-photon emission computed tomography (SPECT) in Japan since 2005. The purpose of this study was to evaluate the safety of and tolerance to thallium-201 myocardial perfusion SPECT with intravenous adenosine infusion in Japanese patients with suspected coronary artery disease. METHODS AND RESULTS: Two hundred and six consecutive patients who underwent an adenosine infusion (120 mug . kg(-1) . min(-1)) SPECT at Sumitomo Besshi Hospital (Niihama, Japan) were investigated. The effects of adenosine infusion were monitored for each patient. A coronary angiography was performed in 81 patients. Adenosine infusion significantly decreased blood pressure and increased heart rate. Adverse reactions were observed in 161 patients (78.2%). Most reactions were transient, disappearing soon after the termination of adenosine infusion. No serious adverse reactions, such as acute myocardial infarction or death, occurred. Adenosine infusion was terminated in 3 patients (1.5%) because of near syncope or sustained 2:1 atrioventricular block. Electrocardiographic changes occurred in 15 patients (7.3%). Self-assessed scoring after SPECT showed that the patients were very tolerant (74.6% of 177 patients) of adenosine infusion myocardial SPECT. The sensitivity and specificity were 75.0% and 69.7%, respectively. CONCLUSIONS: Adenosine infusion myocardial SPECT is safe and well tolerated in the Japanese population, despite the frequent occurrence of minor adverse reactions.

Genotoxicity of thallium-201 in patients with angina pectoris undergoing myocardial perfusion study.

Thallium-201 (201Tl) has been widely used as a nuclear reagent for myocardial blood flow imaging. The purpose of this study was to investigate genotoxic effects of 201Tl in patients with angina pectoris (n = 21), who had undergone myocardial perfusion imaging. Lymphocytes were isolated from each patient before, and 3, 30 and 90 days after 201Tl administration (111 MBq, 3 mCi) and were analyzed for chromosomal aberrations, sister chromatid exchanges, mitotic index and replicative index. There were significant increases in chromosomal aberrations and sister chromatid exchanges 3 days after 201Tl administration (p < 0.001), although no difference was noted in these values after 30 and 90 days (p > 0.05). Moreover, decreased mitotic index and replicative index were noted after 3 days of 201Tl administration (p < 0.001). These results suggest that the administration of 201Tl for myocardial blood flow imaging may induce genetic damage.

Acute generalized exanthematous pustulosis due to thallium.

Acute generalized exanthematous pustulosis (AGEP) is characterized clinically by fever, pruritus and acute pustular eruption. Usually a drug is found to be the responsible agent. We present a patient who experienced an acute generalized exanthematous pustulosis due to radioactive thallium. The eruption cleared rapidly after discontinuation of the drug and systemic corticosteroid therapy.

Prognostic value of exercise thallium-201 imaging in a community population.

BACKGROUND: The prognostic value of exercise thallium-201 imaging has been well established in referral patient populations at tertiary care centers, but these results may be influenced by referral bias. METHODS: This study was performed to evaluate the prognostic value of thallium imaging in a community-based population of 446 residents of Olmsted County, Minn. Eleven variables were prospectively selected and tested for their associations with outcome end points. RESULTS: Four variables (age, history of myocardial infarction, number of abnormal thallium segments on the postexercise images, and increased thallium lung uptake) contained the most independent prognostic information. For the end point overall mortality rate, the multivariate chi-square values were 17.2 (p < 0.0001) for age and 20.9 (p < 0.0001) for the number of abnormal thallium segments on the postexercise images. Five-year survival rate for patients older than the median age of 59 years with an abnormal scan was 84% versus 97% for patients < or = 59 years of age with a normal scan. CONCLUSION: Exercise thallium imaging was useful for prognostic purposes in this relatively low-risk community population, confirming the findings of referral population studies.

Biokinetics of thallium-201 in normal subjects: comparison between adenosine, dipyridamole, dobutamine and exercise.

UNLABELLED: There are currently four common types of stress used with thallium-201 imaging in the diagnosis of coronary artery disease and risk assessment. The objective of this study was to examine the thallium biokinetics during exercise, adenosine, dipyridamole and dobutamine stress testing in 15 healthy volunteers. METHODS: Each subject underwent planar 201Tl imaging during maximal treadmill exercise testing, adenosine infusion (140 micrograms/kg/min for 6 min), dipyridamole infusion (142 micrograms/kg/min for 4 min) and dobutamine infusion (40 micrograms/kg/min). RESULTS: Absolute myocardial thallium activity was greater after pharmacologic testing than exercise, (p < 0.001 each). Thus, the activity was 505 counts/pixel with adenosine, 491 counts/pixel with dipyridamole, 517 counts/pixel with dobutamine and 409 counts/pixel with exercise. The myocardial thallium clearance was lower with pharmacologic testing than exercise; 9.7%/hr with adenosine, 9.9%/hr with dipyridamole, 11.3%/hr with dobutamine and 13%/hr with exercise (p < 0.01 each). The thallium uptake and clearance in the lung and liver were also greater with pharmacologic stress testing than exercise (p < 0.05). CONCLUSIONS: Thus, thallium biokinetics are different during pharmacologic stress testing with adenosine, dipyridamole and dobutamine than during exercise. Diagnostic criteria for quantitative analysis of myocardial perfusion imaging must therefore be specific for the type of stress used.

Safety of single-site adenosine thallium-201 scintigraphy.

The diagnostic accuracy, safety and tolerance of adenosine thallium scintigraphy have been reported using a 2-site intravenous infusion with either a titrated or fixed-dose protocol. A single-site infusion would considerably simplify the test procedure, but its safety must be established before it can be recommended. Accordingly, 400 consecutive patients who had adenosine and thallium-201 administered through the same intravenous line were classified into 2 groups. Group I (n = 201) patients received a 7-minute titrated intravenous infusion of adenosine, with an initial dose of 50 micrograms/kg/min that increased at 1-minute intervals to a maximum of 140 micrograms/kg/min. Group II (n = 199) patients received a fixed dose of adenosine at 140 micrograms/kg/min for 6 minutes. Adenosine significantly (p < 0.001) increased heart rate and decreased systolic blood pressure by similar amounts in both groups. Adverse effects occurred more often (88 vs 71%, p < 0.001) and started earlier (2.8 vs 3.6 minutes, p < 0.001) in group II. There was no significant difference in the occurrence of second- and third-degree atrioventricular block between the 2 groups (4.0 vs 5.0%); however, chest pain, flushing and nausea were all more frequent in group II. Severe side effects were seldom seen in either group and occurred in 9 group I and 8 group II patients. Scintigraphic findings were similar in both groups. Transient perfusion defects were seen more often in patients with than without second- or third-degree atrioventricular block (42 vs 21%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of accuracy for detecting coronary artery disease and side-effect profile of dipyridamole thallium-201 myocardial perfusion imaging in women versus men.

Intravenous dipyridamole planar thallium-201 imaging is a safe and effective test for detection and prognosis of coronary artery disease (CAD) in the general population. The relative diagnostic accuracy and side-effect profile of dipyridamole thallium-201 stress imaging in women is not defined. Forty-three consecutive female and 71 male patients who underwent dipyridamole thallium-201 imaging (0.56 mg/kg) within 3 months of cardiac catheterization were studied. Scans were considered abnormal if fixed or reversible perfusion defects were detected. Stenosis severity of greater than or equal to 50% luminal diameter reduction of any artery defined CAD. Overall sensitivity for detection of CAD was 0.87 in women and 0.94 in men; specificity was 0.58 in women and 0.63 in men (p = not significant). Sensitivity for detection of 1-vessel CAD was 0.60 in women and 0.94 in men (p = 0.001). The sensitivity for detection of multivessel CAD (with or without surgical revascularization) was 1.0 and 0.94 in women and men, respectively. Adverse effects were reported in 62% of women and in 38% of men (p = 0.01). There was no significant difference in the incidences of chest pain, headache, nausea, flushing or electrocardiographic changes. The incidences of severe ischemia and dizziness were higher in women. Possible explanations for this difference in adverse effects include gender differences in the volume of distribution of dipyridamole due to varied fat-to-muscle ratios and different subjective nocioceptive sensitivities to the effects of dipyridamole. Overall sensitivity and specificity are comparable between the sexes.

Radiation dose rates from adult patients undergoing nuclear medicine investigations.

Adult patients undergoing nuclear medicine investigations may subsequently come into close contact with members of the public and hospital staff. In order to expand the available dosimetry and derive appropriate recommendations, dose rates were measured at 0.1, 0.5 and 1.0 m from 80 adult patients just before they left the nuclear medicine department after undergoing one of eight 99Tcm studies, an 123I thyroid, an 111In leucocyte or a 201Tl cardiac scan. The maximum departure dose rates at these distances of 150, 30 and 7.3 microSv h-1 were greater than those found in similar published studies of adult and paediatric patients. To limit the dose to an infant to less than 1 mSv, an 111In leucocyte scan is the only investigation for which it may be necessary to restrict close contact between the infant and a radioactive parent, depending on the dose rate near the surface of the patient, the parent's habits and how fretful is the infant. It is unlikely that a ward nurse will receive a dose of 60 microSv in a working day if caring for just one radioactive adult patient, unless the patient is classified as totally helpless and has undergone a 99Tcm marrow, bone or brain scan. The data and revised calculations of effective exposure times based on a total close contact time of 9 h in every 24 h period should allow worst case estimates of radiation dose to be made and recommendations to be formulated for other circumstances, including any future legislative changes in dose limits or derived levels.

Multivariate clinical models and quantitative dipyridamole-thallium imaging to predict cardiac morbidity and death after vascular reconstruction.

Patients with peripheral vascular disease have a high prevalence of coronary artery disease and are at increased risk for cardiac morbidity and death after vascular reconstruction. The present study was undertaken to assess the value of 18 clinical parameters, of 7 clinical scoring systems, and of quantitative dipyridamole-thallium imaging for predicting the occurrence of postoperative myocardial infarction or cardiac death. Vascular surgery was performed in 125 patients. Thirteen postoperative cardiac events occurred, including 10 cardiac deaths and 3 nonfatal infarctions. Clinical parameters were not useful in predicting postoperative outcome. All 63 patients with normal scan results or fixed perfusion defects underwent surgery uneventfully, whereas 21% (13/62) of patients with reversible defects had a postoperative cardiac complication. By use of quantitative scintigraphic indexes we found that patients with reversible defects could be stratified into intermediate and high-risk subgroups with postoperative event rates of 5% (2/47) and 85% (11/13), respectively, despite intensive postoperative monitoring and antianginal medication. Thus in patients unable to complete a standard exercise stress test, postoperative outcome cannot be predicted clinically, whereas dipyridamole-thallium imaging successfully identified all patients who had a postoperative cardiac event. By use of quantification we found that patients with reversible defects can be stratified into an intermediate risk subgroup that can undergo surgery with minimal complication rate and a high-risk subgroup that requires coronary angiography.

Thallium-201 scintigraphy after intravenous infusion of adenosine compared with exercise thallium testing in the diagnosis of coronary artery disease.

Adenosine is an endogenously produced compound that has significant effects as a coronary and systemic vasodilator. Previous studies suggest that intravenous infusion of adenosine, coupled with thallium-201 scintigraphy, may have specific value as a noninvasive means of evaluating coronary artery disease. The purpose of this study was to compare the diagnostic value of adenosine thallium testing with that of standard exercise thallium testing. One hundred subjects were studied with exercise thallium imaging and thallium imaging after adenosine infusion, including 47 with angiographically proved coronary artery disease and 53 control subjects. The overall sensitivity of the thallium procedures was 81% for the exercise study and 83% for the adenosine study (p = NS); the specificity was 74% for the exercise study and 75% for the adenosine study (p = NS). The diagnostic accuracy of the exercise study was 77% and that of the adenosine study was 79%. Ninety-four percent of subjects had an adverse effect due to the adenosine infusion; however, most of these effects were mild and well tolerated. All adverse effects abated within 30 to 45 s of the termination of the study, consistent with the very brief half-life of the agent. Thus, thallium-201 scintigraphy after intravenous infusion of adenosine has a diagnostic value similar to that of exercise thallium testing for evaluation of coronary artery disease. Adenosine thallium testing may be particularly useful in evaluating patients unable to perform treadmill exercise testing.

Nuclear medicine patients do not have higher mutant frequencies after exposure to thallium-201.

The HPRT-lymphocyte clonal assay has been used to detect mutants induced in vivo in humans. This method has previously detected a rise in mutant frequency among nuclear medicine patients following exposure to technetium-99m, at a dose corresponding in theory to 5.1 mGy. In the present study, nuclear medicine patients were sampled before and after exposure to thallium-201, corresponding to a whole-body dose of 4.2 mGy. No rise in mutant frequency was found. We suggest that a difference in the effective dose received by the patients' lymphocytes accounts for the apparent contradiction with earlier results.