Residualizing and non-residualizing analogues of low-density lipoprotein as iodine-123 radiopharmaceuticals for imaging LDL catabolism.
Low-density lipoprotein (LDL) labeled via direct iodination or via the radioiodinated residualizing moiety tyramine-cellobiose (TC) were compared in rabbits as potential 123I radiopharmaceuticals for imaging sites of LDL catabolism. The tissue deposition of 131I-TC-LDL after 24 h as determined by dissection was in the major catabolic organs (liver, adrenals, spleen), and its plasma clearance was slower in rabbits with dietary hypercholesterolemia than in normals. 131I-LDL was unsuitable as a metabolic tracer due to redistribution of catabolites and/or loss of the label before protein degradation, which resulted in little accumulation of radioactivity in catabolic organs and high thyroid uptake. The plasma clearance half-time was similar (ca 22 h) for the two compounds in normal rabbits, but was increased to about 36 h for 131I-TC-LDL and decreased to approximately 9 h for 131I-LDL in hypercholesterolemic animals. The were similar with dynamic imaging of control and hypercholesterolemic rabbits using 123I-labeled analogues. 123I-TC-LDL rapidly localized in the liver, with low thyroid accumulation of radioactivity. The hepatic uptake of 123I-LDL was about half that of 123I-TC-LDL, and thyroid sequestration of radioactivity was significant for 123I-LDL but not 123I-TC-LDL. These data suggest that whereas the residualizing 123I-TC-LDL has a pharmacokinetic profile representative of lipoprotein metabolism, the biodistribution of the activity from injected 123I-LDL is complicated by processes other than protein degradation. The results are discussed with regard to nuclear medicine applications in evaluating lipoprotein catabolism in man.
Moerlein
S M
SM
Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Dalal
K B
KB
Ebbe
S N
SN
Yano
Y
Y
Budinger
T F
TF
D000818:Animals; D002475:Cellobiose; D006937:Hypercholesterolemia / Q000000981:diagnostic imaging; D007457:Iodine Radioisotopes; D007553:Isotope Labeling / Q000379:methods; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D011817:Rabbits; D011877:Radionuclide Imaging; D014018:Tissue Distribution; D014439:Tyramine
D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; C038394:tyramine-cellobiose adduct; D002475:Cellobiose; D014439:Tyramine