Cardiac blood-pool scintigraphy using technetium-99m DTPA-HSA: comparison with in vivo technetium-99m RBC labeling

We performed cardiac blood-pool scintigraphy using technetium-99m diethylenetriaminepentaacetic acid human serum albumin [( 99mTc] DTPA-HSA), a newly developed blood-pool agent, in 31 patients with various heart diseases and evaluated its clinical usefulness in comparison with the conventional in vivo 99mTc red blood cell (RBC) labeling. Excellent cardiac blood-pool images were obtained by [99mTc]DTPA-HSA method. Biodistribution studies showed higher accumulation of [99mTc]DTPA-HSA than that of 99mTc RBC in the lungs and liver, but similar count ratios of the cardiovascular blood pool to whole body between the two methods. In ECG-gated end-diastolic images, no quantitatively significant difference was observed in left ventricular target-to-background ratios between these two methods. Left ventricular ejection fraction (LVEF) calculated by [99mTc]DTPA-HSA MUGA method was correlated well with that by contrast LVEF (r = 0.91). No side effects were observed in any patient. In conclusion, cardiac blood-pool scintigraphy using [99mTc] DTPA-HSA is readily performed by single i.v. injection and useful for the assessment of cardiac function.     

Acid-citrate-dextrose compared with heparin in the preparation of in vivo/in vitro technetium-99m red blood cells

Red blood cells labeled in vivo/in vitro with Tc-99m (Tc-99m RBC) were prepared in a series of 21 patients and two normal volunteers. In each subject both heparin and acid-citrate-dextrose (ACD) solutions were used to label tandem blood samples. The immediate preinjection binding efficiency (BE) was then determined. In each of the 23 studies, the ACD preparation yielded superior BE. The average BE was 93.47% (+/- 3.78) with ACD and 87.23% (+/- 4.29) with heparin. With the ACD method the effect of carrier Tc-99 may be as great as a 24% reduction in BE observed when initial eluates from long-ingrowth-time generators were used. Improved image quality with minimal renal and urinary-bladder activity results with ACD labeling. It is concluded that the use of ACD results in superior RBC labeling with less nontarget activity relative to heparin and is preferred over heparin for preparing in vivo/in vitro Tc-99m RBC.     

Scintigraphy of throacic aortic and innominate arterial aneurysms: The value of the 99mTc-pertechnetate first pass study with subsequent in vivo labeling of red blood cell pool

The radionuclide first pass flow study, using ^99mTc-pertechnetate associated with in vivo labeling of RBC is now widely applied for gated cardiac imaging (Strauss et al. 1979). Recently we had an opportnity to use this technique for the rapid demonstration of thoracic aortic and innominate aneurysms.     

Can technetium 99m bisdiethylphosphinoethanebis-t butylisocyanide (99mTc-DEPIC) be used for routine radionuclide ventriculography?

Radionuclide ventriculography is a useful investigation in the evaluation of cardiac function. Generally, in vivo technetium 99m-labelled red blood cells (RBC) yield good quality images in ventriculography. However, it is widely believed that some drugs have an adverse effect on RBC labelling. Zanelli et al. (1987) developed a radiopharmaceutical (technetium 99m bisdiethylphosphinoethanebis-t-butylisocyanide,^99mTc-DEPIC) to obtain better results in patients using such drugs. We untertook a prospective study of 6 patients with cardiovascular and/or pulmonary disease using several kinds of drugs to evaluate imaging of the cardiac blood pool with^99mTc-DEPIC and in vivo labelled^99mTc-RBC. After injection, blood samples were taken, and gated equilibrium blood pool studies were performed. The radiochemical purity of the injected^99mTc-DEPIC varied from 76.4 to 93.6% (mean 86.4%, SD 5.7%). The protein (pre-albumin) binding was 100%. Biological half-life in blood varied from 3.3 to 4.7 h (mean 4.1 h, SD 0.5 h). For^99mTc-RBC no significant blood disappearance was seen for 8 h. The percentage of RBC-bound^99mTc varied from 96.9% to 98.3% (mean 97.0%, SD 0.5%) and was stable for at least 8 h. The heart-to-lung, heart-to-spleen, and heart-to-liver ratios were higher for^99mTc-RBC than for^99mTc-DEPIC. Furthermore,^99mTc-DEPIC showed a significant decline of the ejection fraction with time. Visually, the images with^99mTc-RBC were superior to those with^99mTc-DEPIC, especially a few hours after injection. According to our findings, in vivo labelling of^99mTc-RBC is still the method of choice for routine radionuclide ventriculography. The decline of the ejection fraction, the short blood half-life, and the intense liver uptake make^99mTc-DEPIC less suitable for this purpose.     

Comparison of in vitro RBC labeling with the UltraTag RBC kit versus in vivo labeling

This study compared cardiac-gated equilibrium blood-pool imaging studies using in vitro technetium-99m- (99mTc) labeled red blood cells (RBCs) prepared with the UltraTag RBC kit to in vivo labeling with stannous (pyro- and trimeta-) phosphates. The in vitro labeling procedure takes approximately 25 min and does not require centrifugation to separate free from bound 99mTc. Imaging studies were performed in 30 patients using the in vitro labeling procedure and in 30 patients with in vivo labeling. Regions of interest were placed over the center of the left ventricle, inferior and lateral to the left ventricle (background), and over the right midlung. The mean +/- s.e. in vitro RBC labeling efficiency was 98.5 +/- 0.2%. The heart-to-background ratios were significantly higher with in vitro labeling. The heart-to-background ratios, averaged among two blinded reviewers, were 4.6 and 3.4 for the in vitro and in vivo methods, respectively. The heart-to-lung ratio was generally higher with the in vitro procedure (3.6) than that observed with the in vivo method (3.2) but failed to attain statistical significance (p = 0.059). These results demonstrate the superiority of the in vitro labeling procedure over in vivo labeling for gated equilibrium blood-pool imaging.     

In vivo/in vitro labeling of red blood cells with 99mTc

Red blood cells (RBC) were labeled with ^99mTc in vitro after in vivo pretreatment with a stannous solution. The whole in vivo/in vitro procedure took 30–40 min. Pretinning was carried out by injection of either 6 mg DTPA and 0.6 mg Sn⁺⁺ (Sn-DTPA) or 5 mg pyrophosphate and 0.7 mg Sn⁺⁺ (Sn-PYP). The results of 1,356 patients were evaluated. The labeling yield was 89.7% (mean) after pretinning with Sn-DTPA and 88.2% following Sn-PYP pretreatment, the median values being 94% and 92%, respectively. The new method was successfully used in over 2,000 patients who had a radionuclide-ventriculography and in 38 patients studied for localization of occult gastrointestinal bleeding. Adverse side effects have never been observed.     

High RBC labeling efficiency by controlling pretinning with the modified in vivo/in vitro labeling method.

OBJECTIVE: The image quality for gastrointestinal bleeding studies depends on the efficiency of red blood cell labeling. The in vitro technique has been used widely because of its high labeling efficiency. New data for the modified in vivo/in vitro method are lacking. This study reports on the high labeling efficiency that can be obtained with the modified in vivo/in vitro method and the pitfalls to avoid. METHODS: A consecutive series of 91 labeling studies was analyzed. Different amounts of tin, red blood cell concentrations, and infusions of interfering substances also were studied. RESULTS: A mean efficiency of red blood cell labeling of 97% (80%-99%) was obtained. Only 3 cases showed unacceptable results. Suboptimal results were obtained with amounts of tin below 10 microg SnCl2/kg body weight, a reduced hematocrit, and blood transfusion or infusion of HES solution during pretinning. CONCLUSION: The modified in vivo/in vitro red blood cell labeling technique is performed easily, is useful and is comparable to the gold standard in vitro method, provided that the pretinning period is controlled carefully.     

Tc-99m dextran: a new blood-pool-labeling agent for radionuclide angiocardiography

We have explored the possibility of imaging the cardiac blood pool with dextran (Dx) labeled with Tc-99m (Tc) after Sn2+ reduction. Stannous dextran (SnDx) kits were prepared in advance and labeling was performed by adding Tc-99m. The labeling efficiency was greater than 95%. Technetium-99m dextran (TcDx) was highly stable both in vivo and in vitro. In seven dogs we compared the quality of blood-pool images obtained with TcDx of different molecular weights (4 X 10(4) = Dx-40; 5 X 10(5) = Dx-500; 2 X 10(6) = Dx-2000) and with Tc-99m red blood cells (TcRBC) labeled in vitro, and determined the organ distribution of this new agent by whole-body scanning and blood sampling. TcDx provided high-quality cardiac blood-pool images up to 60 min after injection. The heart-to-lung ratios averaged 3.7 for TcDx-40, 3.9 for TcDx-500, and 5.4 for TcRBC at 60 min. Whereas TcDx-40 showed a relatively rapid initial urinary excretion and TcDx-2000 was degraded rapidly, TcDx-500 demonstrated the best kinetics for blood-pool imaging. Thus, TcDx is a new radiopharmaceutical with high labeling efficiency and stability. It overcomes a number of the limitations of currently used blood-labeling agents and may become useful for blood-pool imaging in man.     

Can technetium 99m bisdiethylphosphinoethanebis-t butylisocyanide (99mTc-DEPIC) be used for routine radionuclide ventriculography?

Radionuclide ventriculography is a useful investigation in the evaluation of cardiac function. Generally, in vivo technetium 99m-labelled red blood cells (RBC) yield good quality images in ventriculography. However, it is widely believed that some drugs have an adverse effect on RBC labelling. Zanelli et al. (1987) developed a radiopharmaceutical (technetium 99m bis-diethylphosphinoethanebis-t-butylisocyanide, 99mTc-DEPIC) to obtain better results in patients using such drugs. We undertook a prospective study of 6 patients with cardiovascular and/or pulmonary disease using several kinds of drugs to evaluate imaging of the cardiac blood pool with 99mTc-DEPIC and in vivo labelled 99mTc-RBC. After injection, blood samples were taken, and gated equilibrium blood pool studies were performed. The radiochemical purity of the injected 99mTc-DEPIC varied from 76.4 to 93.6% (mean 86.4%, SD 5.7%). The protein (pre-albumin) binding was 100%. Biological half-life in blood varied from 3.3 to 4.7 h (mean 4.1 h, SD 0.5 h). For 99mTc-RBC no significant blood disappearance was seen for 8 h. The percentage of RBC-bound 99mTc varied from 96.9% to 98.3% (mean 97.0%, SD 0.5%) and was stable for at least 8 h. The heart-to-lung, heart-to-spleen, and heart-to-liver ratios were higher for 99mTc-RBC than for 99mTc-DEPIC. Furthermore, 99mTc-DEPIC showed a significant decline of the ejection fraction with time. Visually, the images with 99mTc-RBC were superior to those with 99mTc-DEPIC, especially a few hours after injection. According to our findings, in vivo labelling of 99mTc-RBC is still the method of choice for routine radionuclide ventriculography.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of changes in portal collaterals by single photon emission CT: effects of endoscopic injection sclerotherapy

The changes in portal collaterals before and after Endoscopic Injection Sclerotherapy (EIS) for esophageal varices were studied by Single Photon Emission CT (SPECT). SPECT was performed for the intra-abdominal blood pool with 99mTc autologous red blood cells (RBC) in 17 patients with liver cirrhosis before and after EIS. Twenty mCi of 99mTc-RBC labeled by in vivo technique were administered intra-venously and tomographic imaging of the intra-abdominal vascular blood pool was performed as follows. For each subjects, 64 views were obtained over 360 degrees of elliptic rotation at 30 seconds per view. In 15 of 17 patients, blood pool images over coronary vein and/or short gastric vein area were clearly demonstrated on coronary images. In 9 of 15 patients, the pool of coronary vein or short gastric vein was disappeared or decreased after EIS. It is considered that intra-abdominal blood pool SPECT study is clinically useful for following up of hemodynamics of portal collaterals before and after EIS.     

Red blood cell labeling with technetium-99m. Effect of radiopaque contrast agents

Radiographic contrast agents have been reported in the literature to interfere significantly with red blood cell (RBC) labeling in vivo by Tc-99m. Moreover, in the presence of contrast agents, red cells have been known to undergo significant morphologic changes. These observations led to the current RBC labeling study in patients (N = 25) undergoing procedures with the administration of contrast media. Before and after contrast administration, blood samples were drawn from each patient into vacutainer tubes containing heparin and RBC labeling was performed using 1-ml aliquots of these samples following the Brookhaven National Laboratory protocol. The differences in average percentage labeling yield with and without contrast media were not significant. In vivo labeling in hypertensive rats with administration of contrast media up to 600 mg likewise consistently gave high labeling yields at all concentrations. Purported alterations in cell labeling attributed to contrast agents are not reflected in these studies, and other pathophysiologic factors need to be identified to substantiate the previous reports. In vitro study offers a potentially useful and simple method to delineate effects of various agents on cell labeling.     

Blood pool ventriculography with a new technetium-labelled complex (99mTc-DEPIC) : a clinical evaluation

A new, single bolus method of in vivo blood pool imaging using a technetium Tc99m phosphine isocyanide complex (DEPIC) which binds to pre-albumin was evaluated in volunteers (n=4) and patients (n=20). DEPIC was assessed for its safety and possible drug interactions. Its duration of action and quality of ventriculography were compared with imaging using standard in vivo red cell labelling (PYP) during two 3-h scanning periods 1 week apart. DEPIC had a mean plasma halflife of 3.3 h. The count rate over the left ventricle was initially 42% higher with DEPIC than with PYP. However, removal of DEPIC by the liver resulted in equivalent count rates by 1 h, and by 3 h PYP count rates were 22% higher than DEPIC. Immediately post injection mean (SD) difference in the left ventricular ejection fraction between the two methods was 2.4% (7.7%). Satisfactory DEPIC scans were obtained up to 2 h post injection, but by 3 h there was a mean difference of 13% (11.3%). DEPIC was found to be a safe alternative to red all labelling for blood pool angiography, suitable for routine work. The single bolus methodology and high initial count rates offer improved efficiency and a capability for truly emergency scanning.     

Radionuclide-labeled red blood cells: current status and future prospects

Radiolabeling of red cells and their clinical and research application in nuclear medicine constitute an area of continued interest and steady growth during the past two decades. Significant advances have been made so that at the present time, radiolabels with sufficient in vitro and in vivo stability are available for diverse applications. Technetium-99m-labeled red cells in particular have revolutionized the field of cardiovascular nuclear medicine by making possible the external evaluation of various heart parameters with minimum radiation dose or trauma to the patient. Among other areas of study that use 99mTc -RBC are blood pool imaging, detection of vascular malformations, red cell mass determination, detection of gastrointestinal bleeding, and of hemangiomas. Heat-damaged 99mTc -RBC find application in spleen imaging, accessory spleen localization, detection of GI bleeding, and in other areas. A critical evaluation is presented of the various in vitro and in vivo labeling techniques that are currently available for red cell labeling. Even though the presently used procedures provide satisfactory labeled preparations, ideal radioisotopic RBC labels remain to be developed. Intermediate (2-3 days) as well as long-lived (approximately 30 days) radionuclidic labels are highly desirable for a number of clinical procedures where 99mTc is not useful due to its short half-life. A clearer understanding of the mechanistic aspects of various labeling reactions is expected to aid in the design of better and improved RBC labels that will help fulfill various areas of need in nuclear medicine applications. New approaches such as the use of radiolabeled antibodies to red cell antigens, or labeling specific receptor sites in the cell may lead to substantial improvements in the labeling methodology and could yield labeled cells with the least damage and maximum in vivo stability.     

Stoichiometric Tc-99m RBC labeling using stable kit solutions of stannous chloride and EDTA: concise communication

An in vitro Tc-99m labeling method is described, which utilizes stable stock solutions of stannous chloride and disodium edetate (EDTA). The kit procedure requires as little as 1 ml of patient blood, can be performed in only 15 min, and gives labeling yields in excess of 98%. By using EDTA, the binding capacity of RBCs for technetium is sufficient to produce Tc-99m RBC doses with specific concentration greater than 50 mCi/ml for first-pass cardiac studies. Scintigrams reveal a slight amount of bladder activity and splenic uptake, but at no time has the thyroid, stomach, or normal bowel been visualized. The predominant 20-hr blood-clearance half-time results in excellent image quality for over 24 hr--an essential property for following intermittent GI bleeding or for performing repeat cardiac function studies over a several-hour time interval.     

Technetium-99m red blood cell labeling in patients treated with doxorubicin

Radionuclide angiography is useful in monitoring cardiotoxicity of doxorubicin, but in vivo RBC labeling in these patients is believed to be poorer than that in general patients. The left ventricle-to-background activity ratio (R) was not significantly lower in patients treated with doxorubicin (3.24 +/- 1.15, N = 13) than in control patients (3.89 +/- 1.60, N = 14). With both modified in vivo and in vitro labeling, R was significantly improved in patients treated with doxorubicin (4.37 +/- 0.91, N = 8, and 4.37 +/- 1.22, N = 13, respectively). However, with the modified in vivo method, labeling efficiency remained a function of hematocrit, whereas the in vitro method removed this dependency. Both modified in vivo and in vitro labeling result in improved image quality over in vivo labeling in patients treated with doxorubicin, and the choice of method can be based on other factors.     

Blood pool ventriculography with a new technetium-labelled complex (99mTc-DEPIC): a clinical evaluation

A new, single bolus method of in vivo blood pool imaging using a technetium Tc99m phosphine isocyanide complex (DEPIC) which binds to pre-albumin was evaluated in volunteers (n = 4) and patients (n = 20). DEPIC was assessed for its safety and possible drug interactions. Its duration of action and quality of ventriculography were compared with imaging using standard in vivo red cell labelling (PYP) during two 3-h scanning periods 1 week apart. DEPIC had a mean plasma half-life of 3.3 h. The count rate over the left ventricle was initially 42% higher with DEPIC than with PYP. However, removal of DEPIC by the liver resulted in equivalent count rates by 1 h, and by 3 h PYP count rates were 22% higher than DEPIC. Immediately post injection mean (SD) difference in the left ventricular ejection fraction between the two methods was 2.4% (7.7%). Satisfactory DEPIC scans were obtained up to 2 h post injection, but by 3 h there was a mean difference of 13% (11.3%). DEPIC was found to be a safe alternative to red all labelling for blood pool angiography, suitable for routine work. The single bolus methodology and high initial count rates offer improved efficiency and a capability for truly emergency scanning.     

Cardiac chamber imaging: a comparison of red blood cells labeled with Tc-99m in vitro and in vivo

A detailed comparison was performed between the quality of cardiac images obtained using red blood cells labeled in vitro and in vivo. Both methods gave cardiac images of high quality. The in vitro method resulted in subjectively superior images, better intravascular retention of injected radioactivity, and a higher left-ventricle-to-background count ratio (p less than 0.05). The differences in image quality and left-ventricular blood-pool activity were not great, however, and the slight advantage of the in vitro method was offset by a somewhat more complicated preparative procedure. We believe that both agents are suitable for radionuclide imaging of the cardiac chambers.     

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 administired 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%) (P0.01). 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.     

Kit-labeled technetium-99m red blood cells (Tc-99m-RBC's) for clinical cardiac chamber imaging

We have studied 223 consecutive patients by R-wave synchronized cardiac imaging using Tc-99m-RBC's labeled by the Brookhaven kit method. Preparation of the Tc-99m-RBC's is simple and can be accomplished in less than 20 min per patient. The average percent RBC labeling was 96.89%. Only 5 of 223 patients (2.2%) had yields less than 95%. Fifty patients were randomly selected from among the 223 patients for more detailed analysis. Image quality was uniformly excellent with good visualization of the cardiac chambers. The spleen was prominently seen. The average left ventricular chamber to background ratio was 2.69±0.56 (X ± S.D.). Among 12 patients imaged with Tc-99m-RBC's (Brookhaven) in whom blood activity was followed, the blood disappearance could be resolved into two components: a major component (95% of total blood activity) with a t-1/2 of 29 h; and a minor component (5% of total activity) with a t-1/2 of 20 min. Splenic uptake obtained with the aid of a computer system in two of these patients showed progressive uptake in the spleen over the first 30 min after injection, with a plateau thereafter.Purposeful degradation of the Brookhaven kit labeled Tc-99m-RBC's study was accomplished in five patients by adding free TcO ₄ ^– . Even small increments of free Tc-99m-pertechnetate resulted in visual deterioration of the cardiac image. Over the course of this study, the percent of total blood activity on the red blood cells dropped from 99% to 78%, and the average end-diastolic left ventricular (LV) to back-ground (BKG) count ratio dropped from 3.5 to 2.4. Ejection fraction measured from the BKG corrected LV curve decreased very slightly.     

Effect of stannous pyrophosphate red blood cell gastrointestinal bleeding scan on subsequent Meckel's scan.

Both labeled RBC and Meckel's scans have been used to evaluate pediatric patients with gastrointestinal bleeding, sometimes sequentially in the same patient. Particularly in infants, from whom withdrawal of sufficient blood for in vitro RBC labeling is often not possible, in vivo labeling with stannous pyrophosphate is used. However, prior administration of stannous-containing agents is known to alter the in vivo distribution of Tc-99m pertechnetate and to interfere with the subsequent Meckel's scan. The authors report on a Meckel's scan performed on an infant 1 week after a GI bleeding study with Tc-99m and stannous pyrophosphate. The Meckel's scan shows abnormal tracer distribution with absent gastric uptake, rendering the scan uninterpretable. In pediatric patients with gastrointestinal bleeding, a Meckel's scan should be done before labeled RBC imaging.