An improved method for the in vivo labelling of red blood cells with 99mTc in gated cardiac imaging

Red blood cells of 10 patients were labelled with 99mTc by the in vivo method, 5 of the patients were orally administered with 400 mg potassium perchlorate at the time of stannous pyrophosphate injection and 5 ml blood was withdrawn at 10 min postinjection of pertechnetate to determine the labelling efficiency of RBC's. The RBC and plasma volumes were also determined in all patients by the 51Cr method. Our results indicated higher incorporation of injected radioactivity into RBC's in the perchlorate administered group (83.8% +/- 9.2%) compared to the other (58.5% +/- 22.0%) (P less than 0.01). The thyroid and stomach were visualized in the control group, but not in the perchlorate administered group. In routine application, 50 MUGA studies have been done with perchlorate administration with excellent results. In 60 patients without perchlorate administration previous to the present study the EF could not be determined in 6 patients (10%). Our results indicated that potassium perchlorate may be used routinely for in vivo labelling of RBC's to improve the labelling efficiency and the quality of gated cardiac imaging.     

111In-tropolonate labelled platelets; studies in normals and in patients with thrombocytopenia

Human platelets were labelled with aqueous ¹¹¹In-tropolonate in comparison with ¹¹¹In-oxinate. In normals the labelling efficiency with ¹¹¹In-tropolonate was higher (93%±2%) than with ¹¹¹In-oxinate (67%±8%) (P<0.05). In cases of severe thrombocytopenia, lower labelling efficiencies were obtained. In six normals a mean platelet life of 9 days ±3 days and an initial recovery of 59%±15% were obtained. In twelve patients with trombocytopenia the mean platelet life was 4 days±4 days and the initial recovery was 58%±20%. The absolute uptake of radioactivity in spleen and in liver in both groups are reported.     

Evaluation of 99mTc-dextran as a lymphoscintigraphic agent in rabbits

Dextran (clinical grade, average mol. wt. 82,200) was labelled with ^99mTc and the labelling efficiency was checked by paper and thin-layer chromatography and electrophoresis. The amount of free ^99mTcO ₄ ^- was always less than 1%. The radiopharmaceutical was injected ID into the web space in hind legs of ten rabbits (200–600 Ci/0.05 ml). Scintigrams were taken at 10-min intervals up to 3 h in three rabbits. The injection site and the hind legs were massaged after injection in the other seven rabbits and scintigrams were taken at 10-min intervals up to 2 h. Blood samples were obtained at 5, 15, 30, 90 and 120 min in both groups. In addition a 180-min sample, was also taken in the first group. At the end of the study the rabbits were killed and the popliteal lymph nodes and the organs were removed to be weighed, and counted. Our results indicated a high concentration of radioactivity in the popliteal lymph nodes and massage at the injection site increased the average uptake of the popliteal lymph node from 1.12%±0.77% to 4.28%±1.57% at 3 and 2 h, respectively (P<0.001). In scintigrams the lymph channels and the nodes were very well visualised. The blood radioactivity levels were too low to present a background problem. With massage 30% of the injected dose was removed from the injection site in 2 h. We have shown that ^99mTc-dextran is a good radiopharmaceutical for the visualisation of the lymph system and deserves further experimental and clinical studies.     

Effects of nicorandil on cardiac sympathetic nerve activity after reperfusion therapy in patients with first anterior acute myocardial infarction

Purpose Ischaemic preconditioning (PC) is a cardioprotective phenomenon in which short periods of myocardial ischaemia result in resistance to decreased contractile dysfunction during a subsequent period of sustained ischaemia. Nicorandil, an ATP-sensitive potassium channel opener, can induce PC effects on sympathetic nerves during myocardial ischaemia. However, its effects on cardiac sympathetic nerve activity (CSNA) and left ventricular remodelling have not been determined. In this study, we sought to determine whether nicorandil administration improves CSNA in patients with acute myocardial infarction (AMI).Methods We studied 58 patients with first anterior AMI, who were randomly assigned to receive nicorandil (group A) or isosorbide dinitrate (group B) after primary coronary angioplasty. The nicorandil or isosorbide dinitrate was continuously infused for >48 h. The extent score (ES) was determined from ^99mTc-pyrophosphate scintigraphy, and the total defect score (TDS) was determined from ²⁰¹Tl scintigraphy 3–5 days after primary angioplasty. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were determined by left ventriculography 2 weeks later. The delayed heart/mediastinum count (H/M) ratio, delayed TDS and washout rate (WR) were determined from ¹²³I-meta-iodobenzylguanidine (MIBG) images 3 weeks later. The left ventriculography results were re-examined 6 months after treatment.Results Fifty patients originally enrolled in the trial completed the entire protocol. After treatment, no significant differences were observed in ES or left ventricular parameters between the two groups. However, in group A (n=25), the TDSs determined from ²⁰¹Tl and ¹²³I-MIBG were significantly lower (26±6 vs 30±5, P<0.01, and 32±8 vs 40±6, P<0.0001, respectively), the H/M ratio significantly higher (1.99±0.16 vs 1.77±0.30, P<0.005) and the WR significantly lower (36%±8% vs 44%±12%, P<0.005) than in group B (n=25). Moreover, 6 months after treatment, LVEDV and LVEF were better in group A than in group B.Conclusion These findings indicate that nicorandil can have beneficial effects on CSNA and left ventricular remodelling in patients with first anterior AMI.     

Renal excretion of iodine-131 labelledmeta-iodobenzylguanidine and metabolites after therapeutic doses in patients suffering from different neural crest-derived tumours

Iodine-131 labelledmeta-iodobenzylguanidine ([¹³¹I]MIBG) is used for diagnostic scintigraphy and radionuclide therapy of neural crest-derived tumours. After administration of therapeutic doses of [¹³¹I]MIBG (3.1–7.5 GBq) to 17 patients (n=32 courses), aged 2–73 years, 56%±10%, 73%±11%, 80%±10% and 83%±10% of the dose was cumulatively excreted as total radioactivity in urine att=24 h, 48 h, 72 h and 96 h, respectively. Except for two adult patients, who showed excretion of 14%–18% of [¹³¹I]meta-iodohippuric acid ([¹³¹I]MIHA), the cumulatively excreted radioactivity consisted of >85% [¹³¹I]MIBG, with 6% of the dose excreted as free [¹³¹I]iodide, 4% as [¹³¹I]MINA and 2.5% as an unknown iodine-131 labelled metabolite. Cumulative renal excretion rates of total radioactivity and of [¹³¹I]MIBG appeared to be higher in neuroblastoma and phaeochromocytoma patients than in carcinoid patients. Based on the excretion of small amounts of [¹³¹I]meta-iodobenzoic acid in two patients, a possible metabolic pathway for [¹³¹I]MIBG is suggested. The degree of metabolism was not related to the extent of liver uptake of radioactivity.     

Mechanism of 201Tl uptake in tumours

We have studied the mechanism of tumour uptake of ²⁰¹Tl by in vivo and in vitro studies. In a series of patients with breast cancer (n=26), lung cancer (n=56) and lymphoma (n=15), the time course of tumour uptake of ²⁰¹Tl paralleled that in the myocardium with almost identical times of peak uptake being obtained in tumours and myocardium. In a patient with hepatic metastases from colonic cancer undergoing laparotomy, ^99mTc labelled microspheres and ²⁰¹Tl were injected into the hepatic artery and biopsies of metastatic and normal liver tissue obtained. The tumour to normal liver activity ratios for ²⁰¹Tl were one tenth of those for ^99mTc microspheres. In the final part of the study, cells from a lung cancer tissue culture line were incubated for 30 min with ²⁰¹Tl with and without the addition of cardiac glycoside, which acts a sodium potassium pump blocker. The cells exposed to the cardiac glycoside showed markedly decreased uptake of ²⁰¹Tl compared to the cells not so exposed (0.6%±0.1% vs 11.8±0.7.2% of the administered dose). The mechanism of ²⁰¹Tl uptake of tumours is similar to that in the myocardium. Sodium potassium pump activity appears to be more important than tumour blood flow. ²⁰¹Tl uptake may provide a useful means of studying tumour viability.     

Use of iodine-123 metaiodobenzylguanidine myocardial imaging to predict the effectiveness of β-blocker therapy in patients with dilated cardiomyopathy

It is crucial to predict drug effectiveness in chronic disease, such as dilated cardiomyopathy (DCM), in which the left ventricular (LV) function might be improved by -blocker therapy. As the functional improvement effected by -blocker therapy takes more than 2 months, we investigated whether iodine-123 metaiodobenzylguanidine (¹²³I-MIBG) imaging could be used to predict drug effectiveness. We studied 13 patients (11 men and two women; mean age, 43±13 years) with DCM and seven normal subjects (six men and one woman; mean age, 48±16 years). We obtained myocardial single-photon emission tomography (SPET) images 15 min and 4 h after administration of¹²³I-MIBG (111 MBq). Studies were performed in the patients with DCM before and 1 and 3 months after the administration of metoprolol and in the normal subjects. We calculated the regional¹²³I-MIBG washout rate (r-WR) in the SPET image, and the global¹²³I-MIBG washout rate (g-WR) and heart-mediastinum activity ratio (H/M) using the anterior planar image. We classified patients into those showing a 5% increase in LV ejection fraction (LVEF) at 3 months compared with LVEF values before the treatment (group 1,n=7) and those showing a <5% increase in LVEF (group 11,n=6). In group I, the r-WR values at pretreatment and at 1 month and 3 months of treatment, respectively, were 36%±19%, 29%±14%* and 25%±13%* in the anterior segment, 39%±17%, 33%±17%** and 28%±17%* in the lateral segment, 36%±16%, 31%±14%* and 22%±12%** in the septal segment and 40%±11%, 37%±19% and 31%±18%* in the inferior segment; the g-WR was 45%±11%, 43%±10% and 34%±9%^*, respectively (*P<0.05, **P<0.01 vs pretreatment). In group II, there were no significant changes in regional or global parameters during the 3-month period. In normal subjects, the r-WR values in each of the anterior, lateral, septal and inferior segments were significantly lower than those in groups I and II. These values were 18%±9%, 18%±15%, 20%±12% and 21%±15%, respectively. This study demonstrated that with regional assessment¹²³I-MIBG SPET imaging can be used to predict the functional improvement of LVEF at 1 month of -blocker therapy in patients with DCM.     

99mTc-labelling of leucocytes with 99mTc-DPO: a complex developed for myocardial imaging

The lipophilic ^99mTc-DPO complex, developed as a myocardial imaging radiopharmaceutical, was used to label leucocytes. After an incubation of 0.1 ml ^99mTc-DPO (8 g DMPE*2HCl) with mixed leucocytes in plasma, the labelling efficiency was over 70%. During incubation in 5 ml plasma, a loss of activity was found between 20% (1 h) and 35% (3 h) caused by elution. Disturbances of cell viability could not be found with the help of the chemiluminescence test. The in vivo recovery was determined in three dogs and was 45%–50% (0.5 h), 30%–36% (1 h), and 18%–24% (3 h). Autologous ^99mTc-DPO-leucocytes were used on seven patients with suspected osteomyelitis, there were four true negative and three true positive results. The target/nontarget ratio determined by ROI in the positive cases was 1.8 to 2.5 at 3 h after injection.     

Development and biodistribution of <Superscript>188</Superscript>Re-SSS lipiodol following injection into the hepatic artery of healthy pigs

Although intra-arterial radiotherapy with ¹³¹I-labelled lipiodol is a useful therapeutic approach in the treatment of hepatocellular carcinomas, various disadvantages limit its use. Here we describe the development of ¹⁸⁸Re-SSS lipiodol, as well as its biodistribution in the healthy pig after injection into the hepatic artery. The ¹⁸⁸Re-SSS lipiodol was obtained after dissolving a chelating agent, previously labelled with ¹⁸⁸Re, in cold lipiodol. The radiochemical purity (RCP) of the labelling was checked immediately and at 24 and 48 h. The ¹⁸⁸Re-SSS lipiodol was injected into the hepatic artery of six healthy pigs. They were killed 1, 24 and 48 h post injection, for ex vivo counting. An autoradiographic study was performed in three cases. ¹⁸⁸Re-SSS lipiodol was obtained with a yield of 87%±9.1%. The immediate RCP was 93%±3.4%. This radiolabelling was reproducible and stable at 48 h in plasma: 90.6%±1.5% of the activity remained in the lipiodol with an RCP of 91%±4%. Ex vivo counting confirmed the predominantly hepatic uptake and revealed weak lung and intestinal uptake. There was very weak urinary elimination (2.3%±0.5% at 48 h) and a slightly higher level of intestinal elimination (4.8%±1.9% at 48 h). The autoradiographic studies showed ¹⁸⁸Re-SSS lipiodol to be located mainly in sinusoids, like ¹³¹I-lipiodol. By using the method described here, ¹⁸⁸Re-SSS lipiodol can be obtained with a very high yield and a satisfactory RCP. Its biodistribution in the healthy pig is in agreement with data published elsewhere concerning other types of radiolabelling used for lipiodol, except for the very weak urinary and intestinal elimination, which probably indicates better stability of ¹⁸⁸Re-SSS labelling.     

A simple and safe technique for sterile autologous platelet labelling using “Monovette” vials

A simple technique of autologous platelet labelling is described, which allows labelling within 40 min, and has the advantage of low costs, as no laminar air flow is required. Blood (16 ml) was withdrawn into 4 ml ACD, 500 ng prostacyclin was added. After 10 min sedimentation the vials were centrifuged for 5 min at 150 g. The plateletrich plasma in the supernatant was centrifuged at 500 g for 10 min to obtain a platelet pellet. The platelet-poor plasma was preserved in a sterile syringe and the platelet pellet was resuspended in 1 ml tyrode buffer. The cell suspension was labelled at 37° C for 5 min with 100 Ci ¹¹¹In-oxine sulphate and reinjected after dilution with the plasma. Mean labelling efficiency was 90%±3%, mean recovery 2 h after reinjection 76%±3% (mean±SD).     

A chemical method for the labeling of fibrinogen with 99mTc

A new method allowing the labelling of fibrinogen with ^99mTcO ₄ ^- is described. The ^99mTcO ₄ ^- is reduced by stannous chloride in an alkaline medium. After 1 h incubation with fibrinogen, the pH was brought down to 7.1. The study of (1) the pH of the solution, (2) the quantity of the reducer, and (3) the time of incubation allowed us to specify optimal conditions for labeling. The labeling yield varied from 91.68%±6.05% to 95.18%±2.13% according to the method of control used: the precipitation of fibrinogen by (NH₄)₂SO₄ 25% or thin-layer chromatography with methylethylketone as solvent. Clottable radioactivity averaged 72%±4.43%. Column chromatography separated the tracer into two radioactive peaks. The first peak corresponded to the fibrinogen and carried 73.36%±5.8% of the total radioactivity. The total recovered radioactivity amounted to 89.86%±8.07%. Spectroscopic clottability was 88.23%±2.42%.The in vivo stability of the labeling and the molecule was followed for 24 h after intravenous injection. If the radioactivity measured in the 5 min sample was considered to equal 100%, the 24 h sample averaged 32.71%±3.25%, of which 85.68%±2.92% was recovered in the clot. In conclusion, this method enabled us to obtain a stable tracer that we used for routine investigations in man.     

Rapid measurement of blood leakage during regional chemotherapy

In order to avoid complications after regional chemotherapy (isolated hyperthermic perfusion) of the extremities, rapid measurement of blood leakage from the extracorporeal to the systemic circulation is important. A method using technetium-99m in vivo red blood cell (RBC) labelling is reported that provides results within 3 min. Blood samples drawn from the systemic and the extracorporeal circulation were measured for ^99mTc activity using a mobile well counter, and the leakage values calculated. The mean result was 7.6%±6.5%/15 min (n=209). The corresponding flow rate was 100.2±85.7 ml/15 min (mean ± SD). The values for isolation perfusion of the upper and the lower extremities are compared. The leakage results using ^99mTc RBC labelling were correlated with other blood pool markers. Iodine-125 human serum albumin and indium-113 m transferrin were administered in subgroups of 4 and 19 patients simultaneously. Using linear regression, the coefficient of correlation was 0.72 for ^99mTc/^113mIn and 0.58 for ^99mTc/¹²⁵I. Comparison with the alternatives suggests that the rapid method of leakage measurement after ^99mTc RBC labelling can be considered one of the most practicable and reliable methods available.This paper is dedicated to Prof. E. Oberhausen, Homburg/Saar, on the occasion of his 65th birthday Correspondence to: C. Alexander     

Nitrogen-13 ammonia cardiac positron emission tomography in mice: effects of clonidine-induced changes in cardiac work on myocardial perfusion

We explored the feasibility of imaging myocardial perfusion and of demonstrating the flow changes in response to reduction of cardiac work non-invasively in anesthetized mice using high spatial resolution, dedicated small-animal positron emission tomography (microPET). In 31 C57BL/6 mice anesthetized with pentobarbital or isoflurane, ¹³N-ammonia was injected intravenously and images were recorded with microPET from 4 to 20 min. Fifteen mice (group 1) were studied consecutively at baseline (BL) and after reduction of heart rate (HR) with intraperitoneal injection of clonidine (CLN) to investigate effects of CLN-induced reduction of cardiac work on myocardial ¹³N-ammonia uptake. Eight mice (group 2) were imaged repeatedly at BL and eight mice (group 3) twice after CLN to examine reproducibility. Total myocardial ¹³N-ammonia accumulation was determined from the transaxial images and normalized for injected dose (%ID). HR was 412±97 beats/min at BL and 212±44 beats/min after CLN (P<0.0001). In group 1, the %ID significantly decreased from 1.50%±0.27% at BL to 1.29%±0.28% after CLN (P<0.0001). In groups 2 and 3, reproducibility of %ID was good (y=0.96x+0.105, SEE=0.212%, r ²=0.749, P<0.0001). In conclusion, ¹³N-ammonia microPET imaging demonstrated non-invasively a reduction of myocardial perfusion induced by clonidine in mice. We believe this study is of importance as the first report on myocardial perfusion imaging and flow validation in in vivo mouse hearts with a left ventricular size of only 5 mm using ¹³N-ammonia and PET. MicroPET will aid in elucidating cardiac pathophysiology in transgenic mice and monitoring effects of gene therapies on myocardial perfusion.     

Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate. IV. Interaction of 99mTc-DMS and 99Tc-DMS complexes with blood serum proteins

As a crucial step towards understanding the mechanism of localisation of radiopharmaceuticals in specific target organs, the interaction of the radiopharmaceuticals ^99mTc-DMS and ⁹⁹Tc-DMS with blood serum proteins was studied. The interaction of ^99mTc-DMS radiopharmaceutical was examined from two aspects: total protein binding as well as specificity of binding to certain classes of proteins.After in vitro labelling of human sera with ^99mTc-DMS, the following values of bound radioactivity to total serum proteins were determined: 65%±3.2% by gel-filtration chromatography; 72%±4.6% by dialysis; while on the basis of precipitation by perchloric and trichloroacetic acid 72.7%±6.8% and 71%±2.3%, respectively. Distribution of ^99mTc-DMS or ⁹⁹Tc-DMS among serum proteins was analysed by agarose gel electrophoresis of the sera at pH 8.6 after in vivo and in vitro labelling of human sera with ^99m-Tc-DMS, while the same analysis was performed with ⁹⁹Tc-DMS complex after in vitro labelling of human and rat sera as well as after in vivo application to the rats.The results obtained demonstrate that carrier serum proteins investigated by agarose gel electrophoresis were in the migration zone of ₂-, ₁- and ₁-globulins, whereas the radioactivity found in the serum albumin zone was negligible. Interaction of both Tc-DMS complexes with proteins was very similar, and this conclusion was in good correlation with our previously obtained results in investigations concerning the biochemical behaviour of these complexes.     

Value of gated SPECT in the analysis of regional wall motion of the interventricular septum after coronary artery bypass grafting

Purpose The aim of this study was the evaluation of septal wall motion, perfusion and wall thickening after CABG in two groups of consecutive patients, one with grafted left anterior coronary artery and no history of myocardial infarction, and the other with previous anteroseptal myocardial infarction and impaired septal motion before surgery. The issue addressed was the ability of gated SPECT to differentiate between true paradoxical septal motion, characterised by paradoxical wall motion, depressed ejection fraction (EF), poor viability and compromised wall thickening, and pseudo-paradoxical motion, characterised by abnormal wall motion and regional EF but preserved perfusion and wall thickening.Methods One hundred and thirty-two patients with previous anterior myocardial infarction, 82 patients with left anterior descending coronary disease and no history of myocardial infarction and 27 normal subjects underwent rest gated SPECT after ^99mTc-sestamibi injection, according to the standard QGS protocol. Quantitative regional EF, regional perfusion, regional wall motion and regional wall thickening were determined using a 20-segment model.Results Despite the presence of similar regional wall motion impairment in patients with and patients without septal infarction, in terms of regional EF (2.5%±3% vs 1.9%±4.9% p=NS) and inward septal motion (3±4.9 mm vs 2.3±6.1 mm p=NS), significant differences were observed in both perfusion (74.7%±6.2% vs 63.3%±13%, p>0.0001) and regional wall thickening (17.2%±7.4% vs 12.6%±7.2%, p>0.0001).Conclusion Gated SPECT with perfusion tracers can reliably differentiate pseudo-paradoxical from true paradoxical septal motion in patients with previous CABG, and it may be the method of choice for evaluating left ventricular performance in this patient population.     

Efficiency of labelling of red blood cells with technetium-99m after dipyridamole infusion for thallium-201 stress testing

Experimental studies have suggested that dipyridamole may inhibit red blood cell labelling with technetium-99m. To evaluate whether this effect is clinically relevant to the performance of radionuclide ventriculography after dipyridamole-thallium stress testing, in vitro red blood cell labelling was compared immediately before and after thallium-201 stress scintigraphy combined with either dipyridamole infusion (30 patients) or exercise stress (20 patients). Modified in vivo red blood cell labelling efficiency was assessed in a further 36 patients following dipyridamole infusion and was compared with that in 15 patients following exercise stress. The importance of a reversal of the dipyridamole effects by aminophylline was evaluated for in vitro and modified in vivo techniques. The red blood cell labelling efficiency was not significantly different in patients following dipyridamole compared with that obtained following exercise stress for both in vitro (93% ± 4% versus 91% ± 4%) and modified in vivo (87% ± 19% versus 90% ± 6%) techniques. Also, in vitro red blood cell labelling efficiency after dipyridamole was not different to that before stress testing (93% ± 4% versus 92% ± 4%). Reversal with aminophylline had no significant effect on the in vitro labelling efficiency with either the in vitro technique (94% ± 3% with reversal versus 92% ± 5% without) or the modified in vivo technique (91% ± 4% with reversal versus 82% ± 26% without). These results suggest that the red blood cell labelling efficiency is not compromised by the preceding dipyridamole-thallium stress testing but can be optimised by using in vitro labelling. Correspondence to: R.J. Hicks     

Imaging platelet deposition on Dacron bifurcation grafts in man: Quantification by a dual-tracer method using 111In-labeled platelets and 99mTc-labeled human serum albumin

A dual tracer technique using ¹¹¹In-labeled platelets and ^99mTc-labeled human serum albumin was applied to evaluate the thrombogenicity of Dacron bifurcation arterial grafts. The level of platelet accumulation over the whole of the graft was estimated from the ratio of ¹¹¹In-platelet radioactivity deposited on the vascular wall to these radioactivity circulating in the blood pool, i.e., the platelet-accumulation index (PAI). Furthermore, the PAI value was calculated for each pixel in digitized images and the PAI distribution image (PAI image) was reconstructed. Eighteen patients with DeBakey knitted Dacron bifurcation grafts and 11 normal volunteers were studied. Of the 18 patients, 11 had no graft occlusion (group I) and the remaining 7 (group II) had occlusion. The mean PAI value (±SD) over the whole of the graft in group I was 32.6%±33.7% as compared to -8.8%±4.5% in the control group (P<0.01). In group I, the PAI value over the entire graft decreased with the age of the fraft (r=-0.763; P<0.01). In contrast, in group II, platelet accumulation did not diminish with time and persisted beyond the time of which platelet accumulation was no longer found in group I. Moreover, analysis of the PAI images revealed enhanced platelet accumulation on the proximal part of the graft to be more frequent in group II than in group I (6/7 vs 0/11; _c ² = 10.55; P<0.005). The method used for platelet imaging in the present study may be useful in the study of platelet reactions on Dacron arterial prostheses.     

Quantitative thallium-201 scintigraphy after dipyridamole infusion combined with low level exercise in healthy volunteers

To establish test specific normal limits for quantitative analysis of uptake and washout of ²⁰¹Tl after dipyridamole infusion combined with low level exercise, 20 healthy volunteers were studied with low likelihood of coronary artery disease (CAD) assessed by a stepwise probability analysis based on age, sex, symptoms, resting electrocardiogram, and exercise electrocardiography. Likelihood of CAD in these volunteers was calculated as 1%. After dipyridamole infusion combined with low level exercise, one volunteer complained of headache; no other side effects were observed. There were no chest pain complaints. Maximal hemodynamic changes were achieved during the 6th and 7th min of the test. No ST segment depression was recorded. Visual analysis of the ²⁰¹Tl scintigrams was normal in all volunteers. Mean regional washout at 4 h was 44.37%±2.11%. The regional washout in the 70° LAO view (46.65%±1.10%) was significantly higher than in the anterior and 30° LAO views (43.44%±1.50% and 43.02%±1.45%, respectively). Profiles of uptake and washout of ²⁰¹Tl were different after dipyridamole infusion combined with low level exercise as compared to maximal exercise. Thus, in quantitative analysis of ²⁰¹Tl scintigraphy after dipyridamole infusion in conjunction with low level exercise as applied in the present study, it is mandatory to use normal limits of uptake and washout of ²⁰¹Tl derived from healthy volunteers who underwent the same combined protocol.     

Human breast tumor imaging using 111In labeled monoclonal antibody: Athymic mouse model

The monoclonal antibody (MoAb) 323/A3, an IgG1, was raised against the human breast tumor cell line MCF-7 and recognized a 43 Kd membrane associated glycoprotein. Histochemical studies with the antibody detected 75% of metastatic lymph nodes, 59% of primary breast tumors, and showed some staining in 20% of benign breast lesions. For radionuclide imaging, the MoAb 323/A3 was labeled with both ¹²⁵I and ¹¹¹In, via covalently coupled diethylenetriaminepentaacetic acid (DTPA) by the mixed anhydride method. The antibody activity of the DTPA modified 323/A3 was assessed by an immunoassay using viable and fixed MCF-7 target cells. Male athymic nude mice bearing BT-20 human mammary tumors were injected with dual ¹²⁵I/¹¹¹In labeled DTPA 323/A3 via the tail veins. The animals were imaged with a gamma camera equipped with a pinhole collimator at 1–3 h, 1, 2, 3, 4 and 5 days after the tracer administration. On day 5 or 6, the animals were killed, and the biodistribution of the radiotracers was determined for the blood, thyroid, heart, lungs, liver, spleen, kidneys, gastrointestinal tract and tumor. Target to blood ratio at 6 days for the ¹¹¹In tracer was 24:1 in the group with a mean tumor weight of 0.492 g, and 13:1 in another group with a mean tumor weight of 0.1906 g (day 5). However, the ¹²⁵I activity showed only 3.6:1 and 5.4:1 target to blood ratios in the corresponding groups. The larger tumors localized less ¹¹¹In tracer (27.13%±7.57% injected dose/g, Mean±SD) than the smaller tumors (52.75%±22.25% ID/g). Analysis of the gamma images showed that the maximum tracer concentration occurred in the tumors at about 2 to 3 days after intravenous tracer administration. The excellent tumor resolution observed with BT-20 tumors may be due to increased 43 Kd glycoprotein antigen density in this tumor cell line.     

Significance of alteration in biodistribution of labeled lymphocytes exposed to stannous ion

The biodistribution patterns of ^99mTc (^99mTc-lymph) and ¹¹¹In-lymphocytes with [¹¹¹In-(Sn)-lymph] or without (¹¹¹In-lymph) stannous ion treatment was compared in Lewis rats. Syngeneic lymphocytes were labeled with either 125 Ci (4.63 MBq) ^99mTc or 5 uCi (1985 kBq) ¹¹¹In per 2×10⁷ cells. Mean labeling efficiency for ^99mTc and ¹¹¹In was 68.61%±3.90% (SEM) and 87.22%±2.01% (SEM) respectively. ^99mTc-lymph (n=4), ¹¹¹In-lymph (n=6) and ¹¹¹In-(Sn)-lymph (n=6) rats received 2x10⁷ cells and were killed 18 h later. While ^99mTc-lymph demonstrated significantly less localization in spleen, lymph nodes, and blood (P(F)0.01) as compared with ¹¹¹In-lymph, ¹¹¹In-(Sn)lymph also demonstrated a significant difference (P[F]=0.0001) in lymph node accumulation when compared to ¹¹¹In-lymph. As the activity levels utilized are not associated with cell radiation damage, these alterations in biodistribution do not reflect viability or chromosomal damage, but appear related to stannous ion exposure.Support from the American Heart Association-Virginia Affiliate