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.     

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.     

The effects of selected antineoplastic agents on the labeling of erythrocytes with technetium-99m using the UltraTag RBC kit.

OBJECTIVE: Adverse affects of various drugs on the labeling efficiency of RBCs with 99mTc-pertechnetate have been known for several years. This study presents data on the ability of the UltraTag RBC kit to label RBCs with pertechnetate in the presence of various antineoplastic drugs. METHODS: Five different antineoplastic drugs, either alone or in combination, were incubated for 30 min at 37 degrees C with 2-mL samples of whole blood obtained from normal volunteers. Each sample was labeled with pertechnetate and the radiochemical purity determined according to the UltraTag RBC product package insert. Doxorubicin was specifically tested in molar ratios with stannous ion of greater than 1:1 to determine if there was any significant chelation effect that would affect the ability of the kit to label RBCs. In addition, patients were given a bolus injection of doxorubicin and a blood sample was drawn at 30 min to test whether the metabolites had any effect on labeling. RESULTS: The ability of the UltraTag RBC kit to label RBCs with pertechnetate was not adversely affected by the antineoplastic drugs when they were present alone or in combination. Likewise, doxorubicin metabolites did not interfere with the labeling efficiency of 99mTc RBCs using the UltraTag RBC kit. Molar ratios of doxorubicin-to-tin that exceeded 1:1 also had no adverse effects on the labeling efficiency of the UltraTag RBC kit. CONCLUSION: When performing nuclear medicine exams involving the labeling of RBCs with pertechnetate on patients who have received doxorubicin, as well as certain other antineoplastic agents, a high RBC labeling efficiency can be obtained if the UltraTag RBC kit is used.     

The effect of radiographic contrast media on ultrasonically detectable red blood cell aggregation in vitro

We investigated the effect of radiographic contrast media (RCM) on red blood cell (RBC) aggregation by analyzing echogenicity of flowing blood before and after the addition of 2%, 20%, 50% or 95% volume of undiluted meglumine diatrizoate, iohexol, sodium meglumine ioxaglate, or iopamidol and equiosmolar volume concentration of saline. This was done both by stepwise increasing the concentration with minimal mixing and by stepwise decreasing the concentrations with more efficient mixing. All contrast media caused a drop in blood echogenicity after a proper mixing when compared with saline addition. After minimal stirring, both meglumine diatrozoate and iohexol caused a significant increase in blood echogenicity at volume concentrations over 50%. The paper demonstrates that earlier findings of both increased and decreased RBC aggregation following exposure to RCM can be reproduced and that the result depends on experimental setup. In diatrizoate and iohexol RBC aggregates disappear after mixing (increasing the shear rate) or when the RCM/blood mixture is diluted. After dispersement, the abnormal RBC aggregates will not reform.     

Value of MR contrast media in image-guided body interventions

In the past few years,there have been multiple advances in magnetic resonance (MR) instrumentation,in vivo devices,real-time imaging sequences and interventional procedures with new therapies.More recently,interventionists have started to use minimally invasive image-guided procedures and local therapies,which reduce the pain from conventional surgery and increase drug effectiveness,respectively.Local therapy also reduces the systemic dose and eliminates the toxic side effects of some drugs to other organs.The success of MR-guided procedures depends on visualization of the targets in 3D and precise deployment of ablation catheters,local therapies and devices.MR contrast media provide a wealth of tissue contrast and allows 3D and 4D image acquisitions.After the development of fast imaging sequences,the clinical applications of MR contrast media have been substantially expanded to include pre-during-and post-interventions.Prior to intervention,MR contrast media have the potential to localize and delineate pathologic tissues of vital organs,such as the brain,heart,breast,kidney,prostate,liver and uterus.They also offer other options such as labeling therapeutic agents or cells.During intervention,these agents have the capability to map blood vessels and enhance the contrast between the endovascular guidewire/catheters/devices,blood and tissues as well as direct therapies to the target.Furthermore,labeling therapeutic agents or cells aids in visualizing their delivery sites and tracking their tissue distribution.After intervention,MR contrast media have been used for assessing the efficacy of ablation and therapies.It should be noted that most image-guided procedures are under preclinical research and development.It can be concluded that MR contrast media have great value in preclinical and some clinical interventional procedures.Future applications of MR contrast media in image-guided procedures depend on their safety,tolerability,tissue specificity and effectiveness in demonstrating success of the interventions and therapies.     

Poor labeling of Tc-99m red blood cells in vivo in a radionuclide intestinal bleeding study of a patient who had recently undergone frequent blood transfusions

The authors report poor labeling of Tc-99m red blood cells (RBCs) in vivo in a radionuclide intestinal bleeding study of a patient who had recently undergone frequent blood transfusions. The existence of RBC antibodies, as a result of the recent blood transfusions in this patient, was one of the causes of the poor labeling. In radionuclide bleeding studies with patients with recent blood transfusion, Tc-99m HSA-D must be chosen instead of Tc-99m RBCs in vivo.     

In vivo detection of single cells by MRI.

The use of high-relaxivity, intracellular contrast agents has enabled MRI monitoring of cell migration through and homing to various tissues, such as brain, spinal cord, heart, and muscle. Here it is shown that MRI can detect single cells in vivo, homing to tissue, following cell labeling and transplantation. Primary mouse hepatocytes were double-labeled with green fluorescent 1.63-microm iron oxide particles and red fluorescent endosomal labeling dye, and injected into the spleens of recipient mice. This is a common hepatocyte transplantation paradigm in rodents whereby hepatocytes migrate from the spleen to the liver as single cells. One month later the animals underwent in vivo MRI and punctuated, dark contrast regions were detected scattered through the livers. MRI of perfused, fixed samples and labeled hepatocyte phantoms in combination with histological evaluation confirmed the presence of dispersed single hepatocytes grafted into the livers. Appropriate controls were used to determine whether the observed contrast could have been due to dead cells or free particles, and the results confirmed that the contrast was due to disperse, single cells. Detecting single cells in vivo opens the door to a number of experiments, such as monitoring rare cellular events, assessing the kinetics of stem cell homing, and achieving early detection of metastases.     

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.     

Effect of contrast media on red cell filtrability and morphology

The effects of radiological contrast media on red cell morphology and rigidity have been studied. It has been shown that all the contrast agents studied, even when iso-osmolar with plasma, produce changes in red cell morphology, revealing the intrinsic chemotoxicity of contrast medium molecules. The changes are greatest with the most strongly protein-bound medium investigated--meglumine ioglycamide. The effects on red cell rigidity, on the other hand, appear purely a function of osmolality, being entirely reproducible with hyperosmolar solutions of saline. At concentrations iso-osmolar with plasma no effect on deformability is observed. Since the increased rigidity of red cells induced by contrast medium adversely affects blood flow, the use of the new low-osmolality contrast media is particularly recommended in pulmonary angiography and renal arteriography.     

Visualizing cardiac blood pool: Comparison of three labeling methods

The quality of three different labeling methods of visualizing the cardiac blood pool was investigated in 72 patients:^99mtechnetium labeling of red blood cells in vivo or in vitro and human serum albumin. By the simplified technique of in vitro labeling of RBC from the view point of (1) labeling efficiency, (2) activity in the blood, (3) count rates in a standard ROI over the left ventricle and the paracardiac background, (4) ratio of these count rates, and (5) evaluation of image quality, the best results were obtained. HSA and in vivo labeled RBC led to satisfactory results for visual assessment of ventricular performance in most cases. In spite of the slightly higher technical investment involved in the in vitro labeling method this technique appears to be preferable for gated cardiac blood pool studies in view of the excellent labeling quality.     

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.     

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.     

Effect of contrast media on whole blood filtrability. An in vitro comparative study of iohexol, iopamidol and ioxaglate on rat blood

The effects of three contrast media, iohexol, iopamidol and ioxaglate, on rat erythrocytes were compared. Three parameters representative of the rheologic properties of blood were investigated: whole blood filtrability, red cell filtrability and morphology. Whole blood and red cell filtrabilities were both measured using an erythrometer and red cell morphology was observed with an optical microscope. Iohexol and iopamidol were found to cause a significant increase in filtrability indices and to modify the shape of red blood cells. Ioxaglate had less effect on these parameters than did the other two contrast media. The chemical structure seems to be a determining factor for red cell integrity. The study of blood rheology parameters in vitro may be useful as a model predictive of observations on human blood and of hemodynamic consequences.     

The effect of low-osmolar ionic and nonionic contrast media on human blood viscosity, erythrocyte morphology, and aggregation behavior

The effects of three low-osmolar radiographic contrast media (CM)--two nonionic (iohexol, iopamidol) and one ionic (ioxaglate)--on red blood cell (RBC) morphology and aggregation behavior, as well as on blood and plasma viscosity, have been studied. Blood taken from normal, healthy individuals and from patients with uremia was investigated. The authors controlled for the effects of dilution, ionic and nonionic hyperosomolality, and specific chemotoxicity. With ioxaglate, the normal biconcave RBC morphology was fairly well maintained. Iohexol produced a mixture of more-or-less normal cells and echinocytes, while iopamidol yielded only echinocytes. Irregular RBC aggregates have been frequently associated with the presence of echinocyte morphology. In the case of ioxaglate, the capacity of normal blood for rouleaux formation was preserved. This appeared to be compatible with an only moderate decrease in low shear viscosity values. In comparison to the normal control group, RBCs from patients with uremia were clearly more sensitive for hyperosmolar stress. It can be concluded that, in contrast to the nonionic CM, the ionic dimeric compound ioxaglate seems to protect human RBCs against hyperosmolar stress by a mechanism unknown at the present.     

Intracellular labeling of T-cells with superparamagnetic contrast agents

Isolated rat T-cells have been labeled intracellularly, using endocytosis uptake of two superparamagnetic contrast agents, AquaMagl00 and BMS180549, which are both iron-oxide particles coated with dextran. No deterioration of cell proliferation response to mitogen stimulation was observed alter labeling with either superparamagnetic contrast agent. AquaMag100 particles show aggregation and co-precipitation in culture media for T-cells. BMS180549 particles not only produce no observable aggregation or co-precipitation, but also have a higher efficiency for labeling T-cells than AquaPlag100. The efficiency of cell labeling was determined by measuring the decrease in the spin-spin relaxation time of the water proton in cell samples containing 1 × 10⁷ labeled T-cells/milliliter of 2% w/w gelatin. After optimization of the labeling procedures, a shortening of the spin-spin relaxation time by a factor of approximately 7 to 10 has been demonstrated. Under the present experimental conditions, the up-regulation of low density lipoprotein receptor does not increase the labeling efficiency by endocytosis. Our results suggest that intracellular labeling of specific cell types can be achieved with good efficiency and the labeled cells can be detected by magnetic resonance imaging in rat testicles in vivo.     

Effect of various contrast media on platelet aggregation--an in vivo study

Recently, some radiologists using non-ionic contrast media for angiography have noted the increased tendency of thrombus formation in the injection syringe or angiographic catheter contaminated with blood. In vitro studies by some authors have shown that non-ionic contrast media had only a slight anticoagulative effect as compared with ionic contrast media. But the in vivo studies comparing the anticoagulative effect of both ionic and non-ionic contrast media have not been performed previously. We investigated the effect of non-ionic and ionic contrast media on platelet aggregation in 40 patients undergoing angiography. The in vivo study revealed a negligible influence of both non-ionic and ionic contrast media on systemic platelet aggregation. The dose of contrast media also showed no significant correlation with platelet aggregation. Our study suggests that the data from in vitro experiments cannot be extended to in vivo study as for the relationship between contrast media and their anticoagulant effect.     

In vivo labeling of red blood cells with Tc-99m with stannous pyridoxylideneaminates

Several stannous pyridoxylideneaminates were evaluated as stannous ion sources for the in vivo labeling of red blood cells (RBCs) with Tc-99m. In spite of a considerable variety of stannous preparations, rapid and efficient RBC labeling was obtained with each stannous chelate. These results suggest that the role of the ligands is merely to stabilize the divalent state of the tin. The optimal time interval between Sn(II) and 99mTcO4- injections, and the best stannous-ion concentration, was found using stannous pyridoxylideneisoleucine (Sn-P.isoL). Maximal in vivo labeling of the RBCs was obtained with an i.v. dose of 10-20 micrograms Sn(II)/kg of Sn-P.isoL followed 15-30 min later by i.v. administration of pertechnetate.     

Labeling of red blood cells with Tc-99m after oral administration of SnCl2: concise communication

In vivo labeling of red blood cells with Tc-99m was possible after prior oral administration of SnCl2, both in rats and human volunteers. Absorption of oral SnCl2 was low but sufficient for more than 95% labeling efficiency. Prior i.v. administration of stannous chloride is known to induce in vivo labeling of red blood cells with pertechnetate. We have observed that such labeling is possible even after oral administration of stannous chloride. Nearly 95% of the circulating radioactivity and 93.7% of the administered radioactivity was in RBCs 30 min after i.v. injection of 99mTcO4- in rats that were fed 5 mg of stannous chloride (3.13 mg Sn2+ ion) 2 hr before injection. Red blood cells from four human volunteers could bind pertechnetate, both in vitro and in vivo, after oral administration of 100 mg of SnCl2. We have obtained a blood-pool image of the human heart by labeling the RBCs in vivo by this method. We have also studied various parameters affecting the in vivo binding of RBCs with Tc-99m--such as the amount of orally administered SnCl2, the time of injection of radionuclide after oral SnCl2, and the optimum time for the imaging.     

Enhancement of red blood cell proton relaxation with chromium labeling

Nuclear medicine has utilized chromium (Cr) for decades to label red blood cells (RBCs). The purpose of this project was to determine whether sufficient paramagnetic Cr could be bound to red cells to influence proton relaxation significantly. We demonstrated that the T1 and T2 of RBCs can be substantially shortened by labeling them with paramagnetic Cr. Proton relaxation enhancement occurs when red cells are incubated with sodium chromate (VI) over a concentration range of 0.10 mM to 31.6 mM. Labeling with Cr at a concentration of 31.6 mM shortened the T1 of packed cells from 714 msec to 33 msec, and the T2 from 117 msec to 24 msec, as compared with nonlabeled red cells. In vitro hemolysis was significantly increased after labeling at 31.6 mM, but not at lower concentrations. Cr-induced proton relaxation enhancement varied with RBCs from different species, temperature, pH, and length of incubation. T1 values of kidneys containing labeled red cells (303 msec), or labeled cells diluted 10-fold with nonlabeled cells (479 msec), were decreased compared with kidneys containing only nonlabeled cells (600 msec). Finally, preliminary data indicate that the signal intensity of perfused renal tissue is significantly influenced in vivo by infusion of Cr-labeled RBCs. This study demonstrated that Cr labeling of RBCs sufficiently enhances red cell proton relaxation to provide excised organs containing red cells, of which 10% have been Cr-labeled, with shorter T1 and T2 values than organs containing nonlabeled cells. In addition, the ability of labeled cells to alter signal intensity in vivo suggests that Cr may have the potential to become an MRI contrast agent.     

AUR memorial award--1988. MRI enhancement of perfused tissues using chromium labeled red blood cells as an intravascular contrast agent

It has been demonstrated that chromium (Cr) labeling significantly decreases the relaxation times of packed red blood cells (RBCs). In this study, the spin-lattice relaxation time (T1) of human red cells was shortened from 836 ms to 29 ms and the spin-spin relaxation time (T2) shortened from 134 ms to 18 ms, when the cells were labeled at a Cr incubation concentration of 50 mM. Labeling of canine cells at 50 mM resulted in a T1 of 36 ms and a T2 of 26 ms. A labeling concentration of 10 mM produced similar relaxation enhancement, with uptake of 47% of the available Cr, and was determined to be optimal. The enhancement of longitudinal and transverse relaxation rates (1/T1,-1/T2) per amount of hemoglobin-bound Cr are 6.9 s-1 mM-1 and 9.8 s-1 mM-1 respectively, different from those of a pure Cr+3 solution. Labeling cells at 10 mM decreased the survival half-time in vivo from 16.6 days to 4.7 days in dogs. No difference in red cell survival was found with the use of hetero-transfusion versus auto-transfusion of labeled RBCs. Significant shortening of the T1 (912 ms to 266 ms, P = .03) and T2 (90 ms to 70 ms, P = .006) of spleen and the T1 (764 ms to 282 ms, P = .005) and the T2 (128 ms to 86 ms, P = .005) of liver occurred when 10% of the RBC mass of dogs was exchanged with Cr labeled cells. Liver and spleen spin density changes (P greater than 0.23) and muscle spin density and relaxation changes (P greater than 0.4) were insignificant. The in vivo T1 of a canine spleen which had been infarcted did not change following transfusion with labeled cells, where the T1 of liver did shorten. We believe this preliminary study suggests that Cr labeled red cells may have the potential to become an intravascular magnetic resonance imaging contrast agent.