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Modification of low-density lipoprotein during radiolabeling with 99mTc using three labeling methods
1Department of Nuclear Medicine, Medical University of Vienna, Vienna, Austria. grazyna.sobal@meduniwien.ac.at
Summary
Radiolabeling low-density lipoprotein (LDL) with technetium-99m (99mTc) results in oxidative modification, making native-LDL imaging impossible. The ascorbic acid method offers some protection against LDL modification during labeling.
Area of Science:
- Biochemistry
- Radiochemistry
- Cardiovascular Research
Background:
- Native low-density lipoprotein (LDL) uptake differs from modified LDL scavenging in atherosclerosis.
- The impact of LDL preparation and radiolabeling on its structure and imaging is not well understood.
Purpose of the Study:
- To investigate whether 99mTc-labeled LDL represents native or modified LDL.
- To evaluate the influence of different 99mTc labeling methods on LDL oxidation.
Main Methods:
- Compared three 99mTc labeling methods (dithionite, borohydride, ascorbic acid).
- Assessed oxidation-relevant parameters: lag-time, TBARS, REM, baseline dienes, lipid peroxides, amino-groups, and thiol-groups.
- Expressed results as percentage of freshly isolated native LDL or control LDL.
Main Results:
- All three labeling methods induced some degree of LDL oxidative modification.
- Baseline dienes were most affected by borohydride and ascorbic acid methods.
- Lag-time increased with borohydride but decreased with ascorbic acid; no change with dithionite.
- TBARS levels increased with dithionite and borohydride, but decreased with ascorbic acid.
- Thiol groups increased with dithionite, slightly with ascorbic acid, and decreased with borohydride.
- Lipid peroxide generation increased only with the borohydride method.
- Relative electrophoretic mobility (REM) increased with dithionite and borohydride methods.
Conclusions:
- All tested 99mTc labeling methods result in oxidatively modified LDL.
- Imaging native LDL using 99mTc-labeled LDL is not feasible.
- The ascorbic acid method demonstrates antioxidant properties and offers some protection against LDL modification.
