99mTechnetium-labeled low density lipoprotein: receptor recognition and intracellular sequestration of radiolabel

• Published in: Journal of lipid research 1991-01, Vol.32 (1), p.1-8
• Main Authors: Lees, AM, Lees, RS
• Format: Article
• Language: English
• Subjects: Affinity Labels; ANIMAL CELLS; ANIMALS; ARTERIOSCLEROSIS; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOCHEMICAL REACTION KINETICS; CAMERAS; CARDIOVASCULAR DISEASES; CELL CONSTITUENTS; Cells, Cultured; CONNECTIVE TISSUE CELLS; CYTOPLASM; Cytoplasm - metabolism; DAYS LIVING RADIOISOTOPES; DIAGNOSIS; DISEASES; DRUGS; ELECTRON CAPTURE RADIOISOTOPES; FIBROBLASTS; GAMMA CAMERAS; HOURS LIVING RADIOISOTOPES; Humans; INTERMEDIATE MASS NUCLEI; IODINE 125; IODINE ISOTOPES; Iodine Radioisotopes; ISOMERIC NUCLEI; ISOMERIC TRANSITION ISOTOPES; ISOTOPES; KINETICS; LABELLED COMPOUNDS; LIPIDS; LIPOPROTEINS; Lipoproteins - metabolism; Lipoproteins, LDL - metabolism; MAMMALS; MAN; MEMBRANE PROTEINS; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; PRIMATES; PROTEINS; RADIOISOTOPES; RADIOLOGY AND NUCLEAR MEDICINE; RADIOPHARMACEUTICALS; REACTION KINETICS; RECEPTORS; Receptors, LDL - metabolism; SOMATIC CELLS; Technetium - metabolism; TECHNETIUM 99; TECHNETIUM ISOTOPES; VASCULAR DISEASES; VERTEBRATES; YEARS LIVING RADIOISOTOPES 550601 > Medicine-- Unsealed Radionuclides in Diagnostics
• ISSN: 0022-2275; 1539-7262
• DOI: 10.1016/S0022-2275(20)42238-2

99MTechnetium-labeled low density lipoprotein (99MTc-labeled LDL) was developed to detect atherosclerosis by external imaging with the gamma scintillation camera (Lees, et al. J. Nucl. Med. 1985. 26: 1056-1062; Lees, et al. Arteriosclerosis. 1988. 8: 461-470). The present study examined high affinity LDL receptor recognition and intracellular sequestration of 99MTc-labeled LDL by fibroblasts. There were no significant differences between 99MTc-labeled LDL and 125I-labeled LDL in binding parameters or percent inhibition of accumulation, which indicated that 99MTc labeling did not alter receptor recognition of LDL. At 4 degrees C the Kd (+SE) for 99MTc-labeled LDL and 125I-labeled LDL, respectively, was 1.52 +/- 0.24 and 1.45 +/- 0.14 micrograms/ml; Bmax (+/- 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 99MTc-labeled LDL accumulation from 0-6 h and the positive slope from 6-24 h indicated that radiolabel that entered cells as 99MTc-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 99MTc-labeled LDL was recognized by the LDL receptor equally as well as 125I-labeled LDL, it should be useful not only for imaging atherosclerosis, but also for quantitatively determining sites of utilization and degradation of LDL.