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Title: Uptake of perfusion imaging agents by transplanted hearts: an experimental study in rats

Abstract

There is a need for a reliable noninvasive marker of rejection in transplanted hearts. Endomyocardial biopsy is now the universally accepted diagnostic method of choice, but the invasiveness of the procedure and the limited size of the sample obtained makes this method far from ideal. As coronary blood flow may be expected to decrease during acute rejection, there has been interest in thallium-201 chloride (T1), a perfusion marker, as an imaging agent for diagnosing cardiac rejection. Hexakis(t-butylisonitrile)-technetium (Tc-TBI) is a representative of a new class of radiopharmaceuticals proposed as perfusion markers. We have compared the uptake of these imaging agents in a rat model of cardiac transplantation. Uptake of Tc-TBI as well as of T1 was significantly lower in rejecting than in nonrejecting hearts. This change was found in both left (LV) and right (RV) ventricles. Allografts in animals treated with cyclosporine (CyA) showed less severe rejection and higher uptakes of both imaging agents as compared to unmodified rejection. Our results suggest that perfusion imaging with these radionuclides is a potentially useful approach to the problem of detecting allograft rejection.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Buffalo Veterans Administration Medical Center, NY (USA)
OSTI Identifier:
6173472
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Surg. Res.; (United States); Journal Volume: 46:2
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; GRAFT-HOST REACTION; DIAGNOSIS; HEART; TRANSPLANTS; RADIOPHARMACEUTICALS; UPTAKE; BIOLOGICAL MARKERS; BIOLOGICAL MODELS; BLOOD FLOW; MYOCARDIUM; ORGANOMETALLIC COMPOUNDS; PERFUSED ORGANS; RATS; TECHNETIUM ISOTOPES; THALLIUM 201; ANIMALS; BETA DECAY RADIOISOTOPES; BODY; CARDIOVASCULAR SYSTEM; DAYS LIVING RADIOISOTOPES; DRUGS; ELECTRON CAPTURE RADIOISOTOPES; HEAVY NUCLEI; ISOMERIC TRANSITION ISOTOPES; ISOTOPES; LABELLED COMPOUNDS; MAMMALS; MUSCLES; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANS; RADIOISOTOPES; RODENTS; SECONDS LIVING RADIOISOTOPES; THALLIUM ISOTOPES; VERTEBRATES; 550601* - Medicine- Unsealed Radionuclides in Diagnostics

Citation Formats

Bergsland, J., Carr, E.A. Jr., Carroll, M., Feldman, M.J., Kung, H., and Wright, J.R. Uptake of perfusion imaging agents by transplanted hearts: an experimental study in rats. United States: N. p., 1989. Web. doi:10.1016/0022-4804(89)90225-4.
Bergsland, J., Carr, E.A. Jr., Carroll, M., Feldman, M.J., Kung, H., & Wright, J.R. Uptake of perfusion imaging agents by transplanted hearts: an experimental study in rats. United States. doi:10.1016/0022-4804(89)90225-4.
Bergsland, J., Carr, E.A. Jr., Carroll, M., Feldman, M.J., Kung, H., and Wright, J.R. 1989. "Uptake of perfusion imaging agents by transplanted hearts: an experimental study in rats". United States. doi:10.1016/0022-4804(89)90225-4.
@article{osti_6173472,
title = {Uptake of perfusion imaging agents by transplanted hearts: an experimental study in rats},
author = {Bergsland, J. and Carr, E.A. Jr. and Carroll, M. and Feldman, M.J. and Kung, H. and Wright, J.R.},
abstractNote = {There is a need for a reliable noninvasive marker of rejection in transplanted hearts. Endomyocardial biopsy is now the universally accepted diagnostic method of choice, but the invasiveness of the procedure and the limited size of the sample obtained makes this method far from ideal. As coronary blood flow may be expected to decrease during acute rejection, there has been interest in thallium-201 chloride (T1), a perfusion marker, as an imaging agent for diagnosing cardiac rejection. Hexakis(t-butylisonitrile)-technetium (Tc-TBI) is a representative of a new class of radiopharmaceuticals proposed as perfusion markers. We have compared the uptake of these imaging agents in a rat model of cardiac transplantation. Uptake of Tc-TBI as well as of T1 was significantly lower in rejecting than in nonrejecting hearts. This change was found in both left (LV) and right (RV) ventricles. Allografts in animals treated with cyclosporine (CyA) showed less severe rejection and higher uptakes of both imaging agents as compared to unmodified rejection. Our results suggest that perfusion imaging with these radionuclides is a potentially useful approach to the problem of detecting allograft rejection.},
doi = {10.1016/0022-4804(89)90225-4},
journal = {J. Surg. Res.; (United States)},
number = ,
volume = 46:2,
place = {United States},
year = 1989,
month = 2
}
  • Technetium 99 m pyrophosphate, Gallium 67 and Thallium 201 uptakes were measured in heterotopically transplanted rat hearts. Five days after transplantation, Technetium 99 m pyrophosphate, and Gallium 67 uptakes were significantly higher in allogeneic grafts than in syngeneic grafts. At an early stage of rejection (three days after transplantation), only Technetium 99 m pyrophosphate uptake in the left ventricle of allogeneic grafts showed a significant difference (p less than 0.04). At five days, Thallium 201 uptake was significantly lower in allo- than syngeneic grafts. There was a positive correlation between radionuclide uptake and histologic degree of rejection for Technetium 99more » m pyrophosphate and Gallium 67 while Thallium 201 uptake correlated negatively. Analysis of variance revealed that hearts with no or minimal rejection had statistically different uptakes than hearts with mild to moderate rejection. These results suggest that uptake of imaging agents might be useful in the diagnosis of rejection of the transplanted heart.« less
  • The physiologic properties of new technetium-99m-labeled myocardial imaging agents (Tc-99m sestamibi, an isonitrile; and Tc-99m teboroxime, a boronic acid adduct of technetium dioxime) are discussed and compared to thallium-201 (Tl-201). Studies with isolated hearts, subcellular fractions and cell cultures indicate that Tc-99m sestamibi, Tc-99m teboroxime and Tl-201 do not share common transport or sequestration mechanisms. Although peak Tc-99m sestamibi myocardial extraction over time is about half that of Tl-201 at equivalent coronary blood flows, the amount of Tc-99m sestamibi that remains in the heart is similar to that of Tl-201 because of its higher retention efficiency. The high retention efficiencymore » for Tc-99m sestamibi also results in minimal redistribution. In contrast, Tc-99m teboroxime myocardial extraction is higher than that of Tl-201, but its retention is less efficient, resulting in relatively rapid washout characteristics which may quickly result in tracer redistribution. During reperfusion after a no-flow period, Tc-99m sestamibi extraction and retention increase, but for Tc-99m teboroxime and Tl-201 these values tend to decrease. All tracers show adequate transport characteristics for perfusion imaging, and differences in transport and retention should lead to the development of new clinical protocols.27 references.« less
  • The comparative effects of altered cellular function and coronary perfusion on myocardial /sup 201/Tl and /sup 83/Rb uptake were evaluated in three groups of isolated rabbit hearts having isovolumic contractions. Paired-indication dilution experiments were performed with /sup 201/Tl, /sup 83/Rb, and /sup 111/In-labeled albumin as an intravascular reference marker. In Group A hearts (n = 12), isotope transport was determined during control, hypoxia, and ischemia. In Group B hearts (n = 8), isotope transport was measured at control flow and again at a 50% and 80% reduction. In Group C hearts (n = 8) only /sup 201/Tl uptake was determinedmore » at control and following coronary reperfusion. Myocardial /sup 201/Tl and /sup 83/Rb transport were not significantly different and were proportional to flow. Although all interventions caused significant hemodynamic alterations, neither tracer was affected by hypoxia at constant flow. Thallium-201 permeation, however, was transiently decreased immediately after coronary reperfusion. We conclude that myocardial uptake of /sup 201/Tl and /sup 83/Rb are similar and directly related to flow, but do not reflect hypoxia induced cellular dysfunction.« less
  • Myocardial sarcoplasmic reticulum (SR) plays a critical role in the regulation of the cytosolic calcium fluctuations that occur during the cardiac cycle. One function of the SR is to lower the calcium concentration so that myocardial relaxation and thus ventricular filling can occur. The aim of the present study was to determine if hyperdynamic sepsis induced a decrease in the capacity of SR to take up calcium. This defect would result in decreased ventricular filling and thus decreased cardiac output, as has previously been shown in isolated perfused working hearts removed from septic rats. Therefore, rats were anesthetized with ether,more » and sepsis was induced by the injection of an aliquot of a fecal homogenate into the peritoneal cavity. Control animals either underwent surgery and received an aliquot of sterilized fecal inoculum (sham) or were untreated (no surgery). On day 2 after surgery, animals were anesthetized with pentobarbital, and hearts were removed, weighted, and SR isolated. The rate of uptake of /sup 45/Ca/sup 2 +/ by SR from septic rats was not depressed compared to controls but in fact was elevated. Maximum /sup 45/Ca/sup 2 +/ accumulated by the SR and Ca/sup 2 +/-stimulated ATPase activity were similar in SR from control and septic hearts. These results suggest that the contractile dysfunction noted in the myocardium in early sepsis is probably not due to inadequate SR removal of Ca/sup 2 +/ during diastole.« less
  • To study the scintigraphic detectability of cardiac rejection, we performed 135 planar myocardial scans (({sup 99m}Tc)pyrophosphate, 85; {sup 201}Tl, 36; {sup 67}Ga, 14) together with endomyocardial biopsies in ten patients for a (mean) 17-mo postoperative period. Specificity of each agent exceeded 89%. Technetium-99m pyrophosphate showed results that significantly correlated with the severity of rejection (p = 0.03), as shown by biopsy, but neither {sup 201}Tl nor 67Ga did so (p = 0.63 and 0.81, respectively). Technetium-99m pyrophosphate showed better diagnostic accuracy (85%) than {sup 201}Tl (69%) and {sup 67}Ga (64%). Technetium-99m pyrophosphate also showed higher negative predictive value (91%) thanmore » thallium (76%) and gallium (69%). Thus, a normal {sup 99m}Tc pyrophosphate scan was usually associated with absence of cardiac rejection. However, all three agents showed unacceptably poor sensitivity (0% to 30%) and thus were not useful as a screening test for cardiac rejection, even when the same agent was used serially in imaging a given patient.« less