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Title: Metabolic imaging with gallium-68- and indium-111-labeled low-density lipoprotein

Abstract

Low-density lipoprotein (LDL) labeled with either gallium-68 ({sup 68}Ga) or indium-111 ({sup 111}In) was evaluated as a potential PET or SPECT radiopharmaceutical for determination of hepatic lipoprotein metabolism in rabbits. Gallium-68 or {sup 111}In was linked to LDL via diethylenetriaminepentaacetic acid (DTPA) with a 25-70% radiochemical yield. Studies in vivo that compared {sup 68}Ga- or {sup 111}In-DTPA-LDL with dilactitol-({sup 125}I)-tyramine LDL and 131I-LDL showed that both {sup 68}Ga- and {sup 111}In-labeled LDL behaved as residualizing radiotracers. Localization of radioactivity within the liver of normal rabbits was visualized clearly with ({sup 68}Ga)DTPA-LDL by PET and with ({sup 111}In)DTPA-LDL by gamma scintigraphy. Significant differences were observed in hepatic uptake of normal compared with hypercholesterolemic rabbits in which low-capacity LDL receptor-mediated catabolism was saturated. Gallium-68 and {sup 111}In-DTPA-LDL are attractive radiopharmaceuticals for noninvasive delineation of tissue LDL metabolism under normal and pathophysiologic conditions.

Authors:
; ; ;  [1]
  1. (Washington Univ. Medical School, St. Louis, MO (USA))
Publication Date:
OSTI Identifier:
6009188
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Nuclear Medicine; (USA); Journal Volume: 32:2
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; LIPOPROTEINS; METABOLISM; RADIOPHARMACEUTICALS; COMPARATIVE EVALUATIONS; DTPA; GALLIUM 68; INDIUM 111; IODINE 125; IODINE 131; LIVER; POSITRON COMPUTED TOMOGRAPHY; RABBITS; SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY; AMINO ACIDS; ANIMALS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BETA-PLUS DECAY RADIOISOTOPES; BODY; CARBOXYLIC ACIDS; CHELATING AGENTS; COMPUTERIZED TOMOGRAPHY; DAYS LIVING RADIOISOTOPES; DIAGNOSTIC TECHNIQUES; DIGESTIVE SYSTEM; DRUGS; ELECTRON CAPTURE RADIOISOTOPES; EMISSION COMPUTED TOMOGRAPHY; GALLIUM ISOTOPES; GLANDS; HOURS LIVING RADIOISOTOPES; INDIUM ISOTOPES; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOMERIC TRANSITION ISOTOPES; ISOTOPES; LABELLED COMPOUNDS; LIPIDS; MAMMALS; MINUTES LIVING RADIOISOTOPES; NUCLEI; ODD-EVEN NUCLEI; ODD-ODD NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PROTEINS; RADIOISOTOPES; RADIOPROTECTIVE SUBSTANCES; TOMOGRAPHY; VERTEBRATES; 550601* - Medicine- Unsealed Radionuclides in Diagnostics

Citation Formats

Moerlein, S.M., Daugherty, A., Sobel, B.E., and Welch, M.J.. Metabolic imaging with gallium-68- and indium-111-labeled low-density lipoprotein. United States: N. p., 1991. Web.
Moerlein, S.M., Daugherty, A., Sobel, B.E., & Welch, M.J.. Metabolic imaging with gallium-68- and indium-111-labeled low-density lipoprotein. United States.
Moerlein, S.M., Daugherty, A., Sobel, B.E., and Welch, M.J.. 1991. "Metabolic imaging with gallium-68- and indium-111-labeled low-density lipoprotein". United States. doi:.
@article{osti_6009188,
title = {Metabolic imaging with gallium-68- and indium-111-labeled low-density lipoprotein},
author = {Moerlein, S.M. and Daugherty, A. and Sobel, B.E. and Welch, M.J.},
abstractNote = {Low-density lipoprotein (LDL) labeled with either gallium-68 ({sup 68}Ga) or indium-111 ({sup 111}In) was evaluated as a potential PET or SPECT radiopharmaceutical for determination of hepatic lipoprotein metabolism in rabbits. Gallium-68 or {sup 111}In was linked to LDL via diethylenetriaminepentaacetic acid (DTPA) with a 25-70% radiochemical yield. Studies in vivo that compared {sup 68}Ga- or {sup 111}In-DTPA-LDL with dilactitol-({sup 125}I)-tyramine LDL and 131I-LDL showed that both {sup 68}Ga- and {sup 111}In-labeled LDL behaved as residualizing radiotracers. Localization of radioactivity within the liver of normal rabbits was visualized clearly with ({sup 68}Ga)DTPA-LDL by PET and with ({sup 111}In)DTPA-LDL by gamma scintigraphy. Significant differences were observed in hepatic uptake of normal compared with hypercholesterolemic rabbits in which low-capacity LDL receptor-mediated catabolism was saturated. Gallium-68 and {sup 111}In-DTPA-LDL are attractive radiopharmaceuticals for noninvasive delineation of tissue LDL metabolism under normal and pathophysiologic conditions.},
doi = {},
journal = {Journal of Nuclear Medicine; (USA)},
number = ,
volume = 32:2,
place = {United States},
year = 1991,
month = 2
}
  • Radiolabeling of low-density lipoprotein (LDL) and external imaging with a gamma camera would offer a means of taking advantage of the metabolic activity of developing atherosclerotic lesions in order to noninvasively detect and determine the extent of atherosclerotic cardiovascular disease. Indium-111-({sup 111}In) labeled LDL was prepared and its purity demonstrated by agarose electrophoresis and ultracentrifugation. In vitro studies with cultured human fibroblasts demonstrated significant inhibition of iodine-125-({sup 125}I) LDL binding to LDL receptors by {sup 111}In-LDL, although this was less than the inhibition produced by unlabeled LDL. Adrenal gland uptake of {sup 111}In-LDL by hypercholesterolemic rabbits was reduced by 86%more » compared to the level of uptake observed in normal rabbits. These results were compatible with downregulation of adrenal LDL receptors in the hypercholesterolemic rabbits. Uptake of {sup 111}In-LDL in the atherosclerotic proximal aorta of hypercholesterolemic rabbits was 2.5 times higher than in normal rabbits. These results suggest that {sup 111}In-LDL has the potential to be a useful agent for external imaging of atherosclerotic lesions and lipoprotein biodistribution.« less
  • A great deal of effort has been made to evaluate and define the role of various diagnostic imaging techniques in various clinical settings that complicate the diagnosis of osteomyelitis. Except possibly in neonates, bone scintigraphy remains generally recommended when there has been no previous osseous involvement. In other cases of chronic disease, previous fracture or trauma, prosthesis, and diabetic foot, In-WBC scintigraphy is generally accepted as an appropriate imaging technique. MRI will play an increasingly important role in diagnosing osteomyelitis and may prove to be an important adjunct in these cases. Research continues to improve our current diagnostic armamentarium. In-IgGmore » appears to avoid practical deficiencies encountered with 67Ga and In-WBC; it remains to be seen what role this agent will play in routine clinical practice. All agents to date image inflammation, not infection, and most require delayed imaging sessions, usually at 24 hours. These shortcomings necessitate further research to develop new radiotracers that can provide useful images within several hours and that are specific for infection, perhaps ultimately delineating the particular microorganism involved.84 references.« less
  • We prospectively compared sequential technetium-gallium imaging with indium-labeled-leukocyte imaging in fifty patients with suspected low-grade musculoskeletal sepsis. Adequate images and follow-up examinations were obtained for forty-two patients. The presence or absence of low-grade sepsis was confirmed by histological and bacteriological examinations of tissue specimens taken at surgery in thirty of the forty-two patients. In these thirty patients, the sensitivity of sequential Tc-Ga imaging was 48 per cent, the specificity was 86 per cent, and the accuracy was 57 per cent, whereas the sensitivity of the indium-labeled-leukocyte technique was 83 per cent, the specificity was 86 per cent, and the accuracymore » was 83 per cent. When the additional twelve patients for whom surgery was deemed unnecessary were considered, the sensitivity of sequential Tc-Ga imaging was 50 per cent, the specificity was 78 per cent, and the accuracy was 62 per cent, as compared with a sensitivity of 83 per cent, a specificity of 94 per cent, and an accuracy of 88 per cent with the indium-labeled-leukocyte method. In patients with a prosthesis the indium-labeled-leukocyte image was 94 per cent accurate, compared with 75 per cent accuracy for sequential Tc-Ga imaging. Statistical analysis of these data demonstrated that the indium-labeled-leukocyte technique was superior to sequential Tc-Ga imaging in detecting areas of low-grade musculoskeletal sepsis.« less
  • The metabolic fate of high density lipoprotein (HDL) sphingomyelin in plasma was studied in rats over a 24-hr period after injection of HDL containing sphingomyelin which was {sup 14}C-labeled in the stearic (18:0) or lignoceric acid (24:0) moiety and {sup 3}H-labeled in the choline methyl groups. Decay of label in plasma followed three phases. The first two phases were similar for both isotopes and both types of sphingomyelin (t1/2 approximately 10 and 110 min). However, during the third phase (from 10 hr after injection), {sup 3}H label disappeared more slowly than {sup 14}C label from 18:0 sphingomyelin, whereas the {supmore » 3}H/{sup 14}C ratio remained relatively constant when 24:0 sphingomyelin was used. Intact, doubly-labeled 18:0 sphingomyelin disappeared from HDL rapidly (t1/2 = 38 min) by tissue uptake and by transfer to very low density lipoprotein (VLDL). VLDL contained up to 12% of the sphingomyelin 1 hr after injection. This is the first demonstration of a transfer in vivo of sphingomyelin from HDL to VLDL. A similarly rapid transfer was also observed in vitro. Some nontritiated, ({sup 14}C)18:0 or ({sup 14}C)24:0 sphingomyelin was redistributed more slowly into HDL. Doubly-labeled phosphatidylcholine appeared in VLDL and HDL within 1 hr after injection and reached 1.8 and 2.1% of the injected {sup 14}C and {sup 3}H in VLDL at 1 hr, and 4.8 and 6.9% in HDL at 3 hr, respectively.« less
  • {sup 99M}Technetium-labeled low density lipoprotein ({sup 99M}Tc-labeled LDL) was developed to detect atherosclerosis by external imaging with the gamma scintillation camera. The present study examined high affinity LDL receptor recognition and intracellular sequestration of {sup 99M}Tc-labeled LDL by fibroblasts. There were no significant differences between {sup 99M}Tc-labeled LDL and {sup 125}I-labeled LDL in binding parameters or percent inhibition of accumulation, which indicated that {sup 99M}Tc labeling did not alter receptor recognition of LDL. At 4 degrees C the Kd (+SE) for {sup 99M}Tc-labeled LDL and {sup 125}I-labeled LDL, respectively, was 1.52 +/- 0.24 and 1.45 +/- 0.14 micrograms/ml; Bmax (+/-more » SE) was 5.45 +/- 0.48 and 4.89 +/- 0.25 ng/well, respectively. Binding was saturated at about 2 micrograms/ml. The complete linearity of {sup 99M}Tc-labeled LDL accumulation from 0-6 h and the positive slope from 6-24 h indicated that radiolabel that entered cells as {sup 99M}Tc-labeled LDL was sequestered; pulse-chase experiments, which measured residual cell-associated radioactivity out to 24 h, also showed that radiolabel was trapped. Because radiolabel sequestration was essentially complete, and because {sup 99M}Tc-labeled LDL was recognized by the LDL receptor equally as well as {sup 125}I-labeled LDL, it should be useful not only for imaging atherosclerosis, but also for quantitatively determining sites of utilization and degradation of LDL.« less