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Development of 68Ga-labelled DTPA galactosyl human serum albumin for liver function imaging

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The hepatic asialoglycoprotein receptor is responsible for degradation of desialylated glycoproteins through receptor-mediated endocytosis. It has been shown that imaging of the receptor density using [99mTc]diethylenetriamine pentaacetic acid (DTPA) galactosyl human serum albumin ([99mTc]GSA) allows non-invasive determination of functional hepatocellular mass. Here we present the synthesis and evaluation of [68Ga]GSA for the potential use with positron emission tomography (PET).

Methods

Labelling of GSA with 68Ga was carried out using a fractionated elution protocol. For quality control thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and size exclusion chromatography (SEC) techniques were evaluated. Stability of [68Ga]GSA was studied in phosphate-buffered saline (PBS) and human serum. For in vivo evaluation [68Ga]GSA distribution in Lewis rats was compared with [99mTc]GSA by using a dual isotope protocol. PET and planar imaging studies were performed using the same scaled molar dose of [68Ga]GSA and [99mTc]GSA. Time-activity curves (TAC) for heart and liver were generated and corresponding parameters calculated (t50, t90).

Results

[68Ga]GSA can be produced with high radiochemical purity. The best TLC methods for determining potential free 68Ga include 0.1 M sodium citrate as eluent. None of the TLC methods tested were able to determine potential colloids. This can be achieved by SEC. HPLC confirmed high radiochemical purity (>98 %). Stability after 120 min incubation at 37 °C was high in PBS (>95 % intact tracer) and low in human serum (∼27 % intact tracer). Biodistribution studies simultaneously injecting both tracers showed comparable liver uptake, whereas activity concentration in blood was higher for [68Ga]GSA compared to [99mTc]GSA. The [99mTc]GSA TACs exhibited a small degree of hepatic metabolism compared to the [68Ga]GSA curves. The mean [68Ga]GSA t90 was higher than the mean t90 for [99mTc]GSA. The mean [68Ga]GSA t50 was not significantly different from the mean t50 for [99mTc]GSA.

Conclusion

This study provides a promising new 68Ga-labelled compound based on a commercially used kit for imaging the functional hepatocellular mass.

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Acknowledgment

Nihon Medi-Physics Co., Ltd. (Tokyo, Japan) is acknowledged for providing the GSA kits.

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria

    Roland Haubner, Anna Helbok, Christine Rangger, Daniel Putzer & Irene J. Virgolini

  2. Department of Radiology, School of Medicine, and the UCSD Molecular Imaging Program, University of California, San Diego, CA, USA

    David R. Vera & Salman Farshchi-Heydari

  3. Universitätsklinik für Nuklearmedizin, Medizinische Universität Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria

    Roland Haubner

Authors
  1. Roland Haubner
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  2. David R. Vera
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  3. Salman Farshchi-Heydari
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  4. Anna Helbok
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  5. Christine Rangger
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  6. Daniel Putzer
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  7. Irene J. Virgolini
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Correspondence to Roland Haubner.

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Haubner, R., Vera, D.R., Farshchi-Heydari, S. et al. Development of 68Ga-labelled DTPA galactosyl human serum albumin for liver function imaging. Eur J Nucl Med Mol Imaging 40, 1245–1255 (2013). https://doi.org/10.1007/s00259-013-2397-8

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  • DOI: https://doi.org/10.1007/s00259-013-2397-8

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