Incorporation of no-carrier added 200,203Pb and 200,201,202Tl in calcium alginate and hesperidin incorporated calcium alginate beads.

When radioisotopes are injected to human body, instantly free radicals are generated due to the interaction of ionizing radiation with water and fluids present in the body. The vehicle carrying radionuclides into human body should therefore be designed in a way which could also eliminate or reduce such possibilities. For the first time we have used free radical scavenger hesperidin, a polyphenolic compound having a benzo-γ-pyrone with a benzene ring moiety for extraction of no-carrier added (NCA) 200,203Pb and 200,201,202Tl. We have modified CA beads by incorporation of a polyphenol (hesperidin) (CA-Hes). This tailor made beads were characterized and tested for their efficacy towards extraction of no-carrier-added lead and thallium radioisotopes from 40MeV α particle irradiated Hg2Cl2 target.

An investigation of the early detection of radiation induced apoptosis by 99mTc-Annexin V and 201thallium-chloride in a lung cancer cell line.

This study aims to investigate the efficacy of in vitro Thallium-201 Chloride (Tl-201) and in vitro and in vivo Tc-99m HYNIC-coupled Annexin V (TAV) in the early detection of radiation induced apoptosis, a proxy indicator of radiation therapy (RT) efficacy. In vitro Tl-201 and TAV accumulation and efflux in non-small cell lung cancer were measured post irradiation at 5 different gamma ray doses. The replication rates (RR) of the cell lines were also measured. The same non-small cell lung cancer line was inoculated into the left femur. In vivo non-invasive Tl-201 and TAV tracer biodistribution studies were performed. Cell RR decrease with increased radiation dose was observed 48 hours after irradiation. Apoptotic cell number was found to have increased in response to 9 Gy and 12 Gy radiation dose. Tl-201 accumulation in the 9 Gy and 12 Gy irradiation groups was found to be higher than the lower irradiation groups. Quick Tl-201 efflux was observed in the 9 Gy and 12 Gy irradiated cells. At 48 hours after irradiation with 9 Gy and 12 Gy, Annexin V accumulation was found to be higher than in the control and 3-6 Gy groups. In vivo mouse model confirmed the increased TAV uptake in implanted tumors for relatively high 9 Gy irradiation as compared to non-irradiated controls. TAV may prove to be an effective radiotracer for early assessment of radiation therapy efficacy, via apoptosis, in human lung cancers.

Absorbed dose distribution in glioma tumors in rat brain after therapeutic intratumoral injection of 201Tl-chloride.

Studies on animals with gliomas inoculated in the brain and treated with intratumoral injections of 201Tl-chloride have previously shown very promising results, with a survival several weeks longer than controls. Total regression was found in some animals, and necrosis was found in all the 201Tl-treated brain tumors. This study was undertaken to estimate the absorbed dose and dose distribution to the tumor based on the localization and clearance properties obtained from images with two high-resolution imaging techniques; pinhole single photon emission computed tomography (SPECT) and beta-camera. The images from the beta-camera were used to calculate the absorbed dose rate, using an in-house-developed, voxel-based Monte Carlo program, based on the EGS4 package. To evaluate the effects of different beta-particle energies on the absorbed dose rate distribution, simulations of medium- and high-energy electrons were conducted. Dose-volume histograms from these simulations show that the energy absorption is very locally distributed for 201Tl and medium energy, whereas high-energy beta emitters show a broader dose-volume distribution. The calculated total absorbed dose of 2-8 Gy in the tumor seems to be relativity low when considering the therapeutic effect that was seen. Further investigations, to determine the cause of the high therapeutic efficacy, are needed.

Twenty-four-hour Tl-201 delayed scan underestimates myocardial viability in patients with acute myocardial infarction after percutaneous transluminal coronary angioplasty.

BACKGROUND: Myocardial viability in area at risk of acute myocardial infarction (AMI) after reperfusion therapy may be underestimated by the 24-hour images due to reverse redistribution (r-RD). METHODS: Subjects were 37 AMI patients in whom Tc-99m pyrophosphate (PYP)/Tl-201 dual-isotope SPECT was positive. The 24-hour delayed scan was performed with only a Tl window. One month later, follow up rest Tl SPECT was performed to evaluate myocardial viability. In early (at PYP/Tl-201 dual-isotope SPECT), 24-hour, and one month follow up Tl studies, Tl uptake in the area of AMI was scored into four grades: 3 as normal to 0 as severely reduced. The scores were evaluated. RESULTS: Among the 37 AMI lesions, there were 16 r-RD, 3 RD, 16 fixed defect (FD) and 2 normal (positive PYP and normal Tl). Mean Tl scores were early; 1.4 +/- 1.1, 24-hr; 0.9 +/- 0.9 and one month; 1.3 +/- 1.1. The 24-hour Tl score was lower than the early and one month Tl scores (p < 0.01). CONCLUSION: Reverse redistribution is frequently observed in an area at risk where PYP SPECT was positive. Nuclear medicine physicians should be aware of the existence of frequent r-RD in Tl scan to avoid the underestimation of myocardial viability in the acute phase after PTCA.

Preoperative dipyridamole-thallium scanning, selective coronary revascularization and long-term survival in patients with critical lower limb ischemia.

BACKGROUND: A large proportion of patients with critical limb ischemia have advanced, often asymptomatic coronary artery disease which is associated with increased perioperative risk and decreased long-term survival. METHODS: We evaluated retrospectively the short and long-term effect of routine dipyridamole-thallium cardiac scanning (DTS) and selective coronary revascularization in 113 consecutive patients who were scheduled for revascularization of the lower extremity. RESULTS: DTS was abnormal in 60 (53.1%) patients and demonstrated a moderate-severe reversible defect in 26 (23.0%) patients. On the basis of DTS and clinical evaluation 33 (29.2%) patients were referred for coronary catheterization. Of these, 9 underwent PTCA and 4 underwent coronary artery bypass, without complications. Surgical revascularization of the limbs was performed in all but two patients. Two (1.8%) patients died postoperatively, three (2.7%) sustained nonfatal postoperative myocardial infarctions. None of the patients who underwent preoperative coronary revascularization suffered a cardiac complication after the peripheral vascular operation. During mean follow-up of 31.7 months, 30 (28.0%) patients died. A moderate-severe reversible defect on DTS was the strongest predictor for shortened survival (Exp(b)=0.61, CI 95%=0.42-0.88; p=0.006). Patients who underwent preoperative coronary revascularization followed a survival curve approaching those without a reversible defect on DTS (mean survival 61+/-8 vs 63+/-4 months; NS) which was significantly better than those with such a defect who did not undergo coronary revascularization (mean survival 34+/-5 months; p=0.03). CONCLUSIONS: While the perioperative benefits of routine preoperative DTS screening in patients with critical limb ischemia, remain debatable, it provides an opportunity for identification and treatment of life-limiting coronary artery disease and improving survival.

Acute congestive heart failure associated with a limited form of systemic sclerosis and primary biliary cirrhosis.

This is the first case of a limited form of systemic sclerosis (ISSc) associated with acute congestive heart failure (CHF) and primary biliary cirrhosis (PBC). A 58-year-old woman with ISSc was admitted because of a sudden onset of CHF. The intravenous administration of nitroglycerine and furosemide ameliorated the symptoms of CHF within 24 hours. She had both anticentromere antibodies and anti-p25 doublet/triplet antibodies to intrahepatic microsomes. Thallium scintigraphy at rest demonstrated significant perfusion defects in both the anteroseptal and inferior myocardium. A coronary angiogram revealed normal coronary arteries and no vasospasm was provoked by the intracoronary administration of acetylcholine. The present case indicates that minute care should thus be taken for the prevention of acute CHF even in patients with a limited form of SSc when thallium perfusion defects are identified.

Nicorandil affords cardioprotection in patients with acute myocardial infarction treated with primary percutaneous transluminal coronary angioplasty: assessment with thallium-201/iodine-123 BMIPP dual SPECT.

BACKGROUND: It has been reported that nicorandil restores blood flow to reperfused myocardium in patients with acute myocardial infarction. However, whether nicorandil might decrease infarct size remains unclear. The aim of this study was to assess the effect of nicorandil on infarct size with thallium-201/beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP) dual-isotope single photon emission computed tomography. METHODS: A total of 62 patients were randomly assigned to receive intravenous nicorandil (4 mg in 5 minutes at admission, immediately followed by 6 mg/hr over a 24-hour period) or placebo. All patients were divided into 4 groups: Group N-a, 16 patients with preexisting angina treated with nicorandil; N-b, 15 patients without preexisting angina treated with nicorandil; C-a, 14 patients with preexisting angina given placebo; C-b, 17 patients without preexisting angina given placebo. Tl-201/BMIPP imaging was performed in the 62 patients within 7 days after admission. Dual-isotope single photon emission computed tomographic images were quantified by severity index with a polar map. RESULTS: The BMIPP severity index was similar among the 4 groups. Only the thallium severity index in the N-a group was significantly less (P<.05). The ratio of the thallium severity index to that of BMIPP in the N-a group was significantly decreased compared with those of the other groups. CONCLUSION: Nicorandil has a protective effect in patients with acute myocardial infarction and preexisting angina treated with primary balloon angioplasty.

Gene therapy using antisense oligodeoxynucleotides labeled with Auger-emitting radionuclides.

Antisense oligomers may be used as a vehicle for carrying a radiation source into a specific location inside a tumor cell. The effects of radioactive-labeled oligodeoxynucleotides (ODNs) may have both direct antisense inhibition and radiation. Thus far, the use of radioactive ODNs has been limited mostly to clinical biokinetic studies. Therapeutic possibilities remain unknown if the basic question of the optimal source of radiation is unanswered. We have shown previously that oligonucleotide therapy can be effective theoretically with the internally labeled ODN phosphorothioates 32P, 33P, and 35S. Here, we expand the selection of radionuclides; we calculated in vivo subcellular tissue distribution for ODN phosphorothioates using the decay characteristics of several beta- and Auger-emitting radionuclides: 32P, 35S, 51Cr, 67Ga, 111In, (1114m)In, 123I, 125I, 131I, and 201Tl. The absorbed nuclear doses of these radiolabeled oligonucleotides were estimated in different cellular dimensions using the subcellular biodistribution data for two oligonucleotides (ISIS 2105 and ISIS 2922). Our results indicate that Auger-emitter isotopes do not give higher absorbed cell nuclear doses than the isotopes suitable for internal labeling of ODN phosphorothioates. However, the biological difference is difficult to estimate. The best isotope for subcellular targeting was 35S, which gives the smallest variation of nuclear dose in the different cell dimensions we studied (nuclear diameter, 6-16 microm; cellular diameter, 12-20 microm). Therefore, we conclude that in oligonucleotide radiotherapy, nuclear targets should be treated with short-range beta-emitters (35S or 33P) that are suitable for the internal labeling of oligonucleotides unless the relative biological effectiveness of Auger-emitters could be remarkably improved. Dual labeling with 32P and 35S may provide therapeutic benefits when treating smaller and larger targets simultaneously. Further in vivo development, especially with 33P and 35S labels for ODNs, is strongly indicated.

Tl-201 uptake and retention in a Warthin's tumor.

We report scan findings of Tl-201 in a case of histologically proved Warthin's tumor. Dual isotopes acquisition was performed in a case of left parotid Warthin's tumor. Both early and delayed Tc-99m-pertechnetate (Tc-99m) images showed increased uptake at the tumor. Tl-201 scan also showed an increase of uptake on the early image and retention on the delayed image. The uptake ratios of Tl-201 were 3.0 (early) and 2.3 (delayed). Scan findings of Tl-201 in a case of Warthin's tumor were similar to those of Tc-99m, and the interpretation of Tl-201 images should be accompanied with Tc-99m images.

The usefulness of stress tests performed in the nuclear medicine department: mathematical methods to assess efficacy at various angiographic endpoints.

Stress myocardial perfusion scintigraphy (SMPS) may be used to amplify or supplant information available from stress electrocardiography (ECG) in directing the clinical management of patients, including the need for coronary angiography. The apparent usefulness of SMPS may depend on referral bias, the stress mode employed and the criterion for disease. We compared markers of ischaemia on quantitative planar SMPS with 201 Tl in 503 referred patients; stress was tailored to the individual patient to include exercise (n = 154), dipyridamole (n = 118) or a combination of the two (n = 231). Four angiographic criteria of increasing severity (A-D) were targeted. The fraction of the population receiving diagnostic benefit was calculated for reversible defects (RD) or lung uptake (LU) in comparison to concurrent ST depression; abnormal baseline tracings and fixed 201Tl defects were regarded as indeterminate. Decision tree induction, a computer-learning algorithm and logistic regression were also used to assess the contribution of 13 scintigraphic and other input variables. In comparison to ST depression, RD showed incremental value in 167 (33%) patients with criterion A, decreasing to 5% with criterion D; LU showed its greatest benefit (21%) with criterion D. Both scintigraphic markers were more useful with dipyrida-mole-based tests than with exercise alone. Decision trees induced at each criterion for disease showed the predominant contribution of scintigraphic results in comparison to clinical and ECG data. In conclusion, in a referred population with a frequent requirement for pharmacological stress, the clinical utility of scintigraphy can be determined by comparison of markers of ischaemia; the results will depend, however on the angiographic criterion for disease.

Predictive value of sequential testing in screening for silent myocardial ischemia in asymptomatic middle-aged men (the ECCIS Project).

The accuracy of sequential testing in the noninvasive diagnosis of coronary artery disease has been established in the symptomatic clinical populations, while little is known about its value when applied to low prevalence groups, such as totally asymptomatic men. To evaluate the accuracy of noninvasive sequential testing in the diagnosis of silent myocardial ischemia, data were collected from exercise electrocardiogram, 201Tl perfusion scintigraphy and radionuclide angiography for 62 totally asymptomatic middle-aged men who underwent coronary arteriography because they were positive for two or more markers of myocardial ischemia as determined by a diagnostic screening of a nonbiased population consisting of 4,842 presumably healthy men aged 40-59 years (the ECCIS Project). The predictive value of serial testing procedures for significant coronary artery obstruction was 35%. Predictive values of an abnormal electrocardiogram associated with either an abnormal 201Tl scintigram, an abnormal isotopic ventriculography, or both were 33, 38 and 31%, respectively. In asymptomatic middle-aged men, there is at least a 50% likelihood that an abnormal radionuclide test is a false-positive result, and the positive predictive value is not enhanced by the concordance of an abnormal 201Tl scintigraphy with an abnormal isotopic ventriculography. Thus, the application of noninvasive sequential testing in screening for asymptomatic coronary artery disease is limited by its low predictive value in accordance with the Bayesian probability theory.

Gastric activity on dipyridamole 201Tl myocardial perfusion imaging: a clinically useful finding.

To determine the potential association of increased 201Tl uptake by the stomach with symptoms referable to gastritis, 39 consecutive patients experiencing chest pain syndromes underwent a routine dipyridamole 201Tl pharmacological stress test. With the patient in a fasting state, dipyridamole was infused intravenously (0.56 mg kg-1), shortly followed by 201Tl infusion and subsequent image acquisition for single photon emission tomography (SPET). The original 32 SPET images over 180 degrees of arc were interpreted without knowledge of clinical data, using a 4-point scoring system. Patients with active symptoms of gastro-oesophageal discomfort (n = 17) were found to have significantly greater 201Tl stomach uptake scores, compared to the little or no uptake in the 22 patients without such active symptoms (P = 0.0001). A stepwise logistic regression analysis was used to determine which factor(s) showed independent predictive value of 201Tl gastric uptake. The only two independent variables identified were the presence of active gastritis symptoms and the use of anti-gastritis medications. Elevated gastric 201Tl uptake may be a clinically useful finding indicative of gastric inflammation that may be of value in the differential diagnosis of chest and epigastric discomfort.

Necrosis of malignant gliomas after intratumoral injection of 201Tl in vivo in the rat.

Fourteen adult Fischer 344 rats were inoculated in vivo unilaterally in the caudate nucleus in the brain with malignant RG 2 glioma cells. By 3 weeks a tumor with a diameter of 3-6 mm normally develops. Ten animals which survived the repeated periods of anesthesia and thallium (Tl) injections (intratumorally three times of 201Tl, 15-23 days after inoculation) showed a prolonged retention of radioactivity at the site of injection with no uptake in other organs except for the kidneys. Singular circumscribed necroses were found post-mortem at the site of injection, comprising malignant glioma tumor tissue, which in six animals was absent, in three animals was markedly reduced in size compared with controls and in one animal had the expected size. In four animals metastases were found in distant locations in the brain; in three of these cases there was a retention of radioactivity in the tumor. The selective necrotizing effect on the tumor cells is interpreted as mainly due to emission of Auger electrons from intracellularly accumulated 201Tl, giving rise to very high energy deposition in the vicinity of the cell nucleus. The results should also have implications for the treatment of human malignant gliomas.

Assessing viable myocardium with thallium-201.

Patients with chronic coronary artery disease and potentially reversible left ventricular dysfunction can often be successfully identified by one or more clinical indicators of myocardial viability, including regional wall motion, systolic wall thickening, regional myocardial perfusion as determined by perfusion tracers, and redistribution of thallium-201. In some patients, however, viable but "hibernating" myocardium will exist even when none of the above are evident. Myocardial viability in this situation can be detected with a high degree of accuracy by the demonstration of preserved metabolic activity by positron emission tomography (PET) scanning. Additionally, modifications of the standard exercise-redistribution thallium protocol may also produce accurate results. These modifications include late thallium-201 redistribution imaging, performed 8-72 hours following initial thallium injection, and thallium reinjection at rest after early (3-4 hours) or late (8-72 hours) redistribution imaging. These methods can identify viable myocardium in many thallium defects that appear to be irreversible on a standard 3-4 hour redistribution image. In addition, serial imaging after administration of thallium-201 at rest may also provide valuable insights into myocardial viability. These imaging modalities have important practical applications in the evaluation and management of patients with coronary artery disease and left ventricular dysfunction.

Comparison of thallium myocardial scintigraphy after exercise and transoesophageal atrial pacing in the diagnosis of coronary artery disease.

Forty-nine patients admitted for assessment of chest pain underwent coronary angiography, planar Thallium 201 myocardial scintigraphy after submaximal exercise (TE) and transoesophageal atrial pacing (TAP). Early hypofixation with redistribution after 4 h indicated ischaemia. The criterion for a myocardial infarction (MI) was a fixed perfusion defect. Coronary angiography was carried out in all patients. Sixteen patients (group 1) had no MI and over 50% narrowing of at least one main coronary vessel. Ischaemia was noted in 10 of the 16 patients during exercise, and in 14 of the 16 patients during atrial pacing. The sensitivity for the prediction of coronary stenosis was 62% for TE and 87% for TAP. Nineteen patients (group 2) had had a previous MI. Reversible ischaemia was noted in 10 of the 19 patients during exercise, and in 11 of the 19 patients during TAP. Four of 14 patients with normal coronary arteries (group 3) had a reversible ischaemia with TE, and three of these same patients developed a positive scan with TAP. The respective specificities were 71% and 78%. Comparison of segmental hypoperfusion after TE and TAP gave identical results in 72 of the 80 segments studied in group I (90%), and in 88 of the 95 segments studied in group 2 (92%). The localizing value of TAP was good in left anterior descending (12 out of 18) and right coronary disease (16 out of 19), but poor in left circumflex stenosis (3 out of 9) misclassified as right coronary disease in four patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prognostic stratification of non complicated acute myocardial infarct. Usefulness of the dipyridamole test with ecg-echo-thallium 201]. / Stratificazione prognostica dell'ima non complicato. Utilità del test al dipiridamolo con ecg-eco-tallio 201.

84 patients (pts) with recent first uncomplicated myocardial infarction underwent during the early post-infarction period, dipyridamole (D) test (EKG-ECHO-THALLIUM) and coronary arteriography in order to verify its feasibility, safety and usefulness in the detection of residual jeopardized but viable myocardium and in the diagnosis of multivessel disease. 69 pts performed a pre-discharge exercise test. During the execution of D test no major side effect occurred. The D-Echo was positive for residual ischemia in 41 pts (48.8%), the D-Thallium in 49 pts (58.3%) and the exercise test in 30 pts (43.5%). Both the imaging techniques allow the recognition of viable myocardium within the infarct zone (homozonal positivity) or outside the infarct zone (heterozonal positivity). The sensibility and specificity for multivessel disease are, respectively: with D-echo 50% and 100%; with D-thallium 60% and 100%; with exercise test 48% and 63%. D test has better diagnostic accuracy than exercise test in detecting multivessel disease; in particular we emphasized the excellent specificity of D-echo and D-thallium test. Poliparametric approach with D-test and exercise test gives a better stratification of the ischemic post-infarction risk.