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Technetium-99m labelled LDL as a tracer for quantitative LDL scintigraphy

I. Tracer purification, in vitro and in vivo long-term stability, in vitro validation and biodistribution

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Abstract

The goal of the present study was to optimize technetium-99m labelling of low-density lipoprotein (LDL) and to investigate the in vitro and in vivo properties of the tracer to determine whether its application for quantitative scintigraphy of hepatic LDL receptor activity is feasible. LDL labelled with iodine-125 by the iodine monochloride method was used as a reference tracer. Comparison of different assessments of radiochemical purity [trichloro-acetic acid precipitation (%ppTCA), paper chromatography, size-exclusion chromatography and chloroform-methanol extraction] exhibited %ppTCA to be superior as a parameter of tracer quality. In spite of a high radiochemical purity immediately after labelling, modifications of 99mTc labelling of LDL did not overcome the poor long-term stability of the tracer. Subsequent dialysis in phosphate buffer over about 3 h sufficiently increased the long-term stability in vitro and in vivo. The competitive recognition of dialysed 99mTc-LDL and 125I-LDL with native LDL by high-affinity binding sites was demonstrated in human hepatoma cells (HepG2) and human fibroblasts. Biodistribution data of simultaneously injected 99mTc-LDL and 125I-LDL in New Zealand White rabbits showed a high uptake of both tracers in tissues with high LDL receptor activity, yet 99mTc-LDL uptake exceeded 125I-LDL uptake by two- to sevenfold. In contrast to 125I-LDL, 99mTc-LDL showed a higher unspecific uptake into the bone marrow and the spleen, suggesting an additional uptake mechanism probably via the scavenger pathway. Curve deconvolution of plasma clearance in five female New Zealand White rabbits and five male hyperlipidaemic patients again showed a marginally different biokinetic behaviour of 99mTc-LDL and 125I-LDL. It is concluded that dialysis of 99mTc-LDL substantially increases long-term stability, which is essential for quantification purposes, and that the dialysed tracer has retained its biological integrity as it is recognized by the LDL receptor in vitro. It remains to be determined to what extent the estimation of hepatic LDL receptor activity by quantitative 99mTc-LDL scintigraphy is influenced by the different biokinetic behaviour of 99mTc-LDL and 125I-LDL.

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Authors and Affiliations

  1. University Clinic of Nuclear Medicine, University of Vienna, Waehringer Guertel 18-20, Vienna, Austria

    Thomas Leitha & Robert Dudczak

  2. Department of Medical Chemistry, University of Vienna, Vienna, Austria

    Marcela Hermann & Manfred Hüttinger

  3. Austrian Research Center, Seibersdorf, Austria

    Peter Angelberger

Authors
  1. Thomas Leitha
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  2. Marcela Hermann
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  3. Manfred Hüttinger
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  4. Peter Angelberger
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  5. Robert Dudczak
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Leitha, T., Hermann, M., Hüttinger, M. et al. Technetium-99m labelled LDL as a tracer for quantitative LDL scintigraphy. Eur J Nucl Med 20, 667–673 (1993). https://doi.org/10.1007/BF00181756

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  • DOI: https://doi.org/10.1007/BF00181756

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