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Rapid blood clearance and lack of long-term renal toxicity of 177Lu-DOTATATE enables shortening of renoprotective amino acid infusion

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Abstract

Purpose

The aim of the study was to investigate the feasibility of shortening the recommended 4-h renoprotective amino acid infusion in patients receiving peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5-fluorouracil. We evaluated the clearance of radiopeptide from the blood, long-term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino acid infusion and renal uptake in patients receiving an abbreviated infusion.

Methods

The whole-blood clearance of 177Lu-DOTA-octreotate (LuTate) was measured in 13 patients receiving PRCRT. A retrospective analysis of short-term and long-term changes in glomerular filtration rate (GFR) in 96 consecutive patients receiving a 4-h infusion was performed. Renal LuTate retention estimated using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid infusion was compared with that in 72 cycles with the 4-h infusion.

Results

LuTate demonstrated biexponential blood clearance with an initial clearance half-time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean increase from baseline; 95 % CI −6.9 to 4.4 ml/min) and no grade 3 or 4 nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after a median follow up of 22 months was 2.2 ml/min per year. There was no significant difference in the renal LuTate retention measured in patients receiving a 2.5-h amino acid infusion compared to those who had a 4-h infusion.

Conclusion

The greatest renal exposure to circulating radiopeptide occurs in the first 1 – 2 h after injection. This, combined with the safety of LuTate PRCRT, allows consideration of an abbreviated amino acid infusion, increasing patient convenience and reducing human resource allocation.

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Acknowledgments

Professor Hicks and Dr. Jackson were supported by a Translational Research Grant from the Victorian Cancer Agency. Dr. K Raghava Kashyap was supported by Endeavour Awards, a venture of Austraining International in partnership with the Department of Education, Employment and Workplace Relations, Government of Australia. We acknowledge the support and inspiration provided to our facility over the past 15 years from the Department of Nuclear Medicine at the Erasmus Medical Centre under the leadership of Professor Eric Krenning.

Conflicts of Interest

None.

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Authors and Affiliations

  1. Centre for Cancer Imaging, Peter MacCallum Cancer Centre, St Andrews Place, Melbourne, 3002, Australia

    Raghava Kashyap, Michael S. Hofman, Peter Eu & Rodney J. Hicks

  2. Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Australia

    Price Jackson

  3. Department of Radiology, Université Laval, Quebec City, Canada

    Jean-Mathieu Beauregard

  4. Department of Biostatistics & Clinical Trials, Peter MacCallum Cancer Centre, Melbourne, Australia

    Diana Zannino

  5. Departments of Medicine and Radiology, The University of Melbourne, Melbourne, Australia

    Michael S. Hofman & Rodney J. Hicks

Authors
  1. Raghava Kashyap
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  2. Price Jackson
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  3. Michael S. Hofman
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  4. Peter Eu
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  5. Jean-Mathieu Beauregard
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  6. Diana Zannino
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  7. Rodney J. Hicks
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Corresponding author

Correspondence to Rodney J. Hicks.

Additional information

R. Kashyap, P. Jackson and M. S. Hofman contributed equally to this work.

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Kashyap, R., Jackson, P., Hofman, M.S. et al. Rapid blood clearance and lack of long-term renal toxicity of 177Lu-DOTATATE enables shortening of renoprotective amino acid infusion. Eur J Nucl Med Mol Imaging 40, 1853–1860 (2013). https://doi.org/10.1007/s00259-013-2504-x

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  • DOI: https://doi.org/10.1007/s00259-013-2504-x

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