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The tumour sink effect on the biodistribution of 68Ga-DOTA-octreotate: implications for peptide receptor radionuclide therapy

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Abstract

Purpose

Tumour sequestration of radiotracer may lead to decreased bioavailability in healthy tissue resulting in lower absorbed radiation dose to critical organs. This study aims to assess the impact of disease burden, body habitus and urinary excretion on the biodistribution of 68Ga-DOTA-octreotate.

Methods

Ten patients with highly varied burden of somatostatin receptor-positive neuroendocrine tumour on 68Ga-DOTA-octreotate positron emission tomography (PET)/CT were selected. Volumes of interest were drawn to derive the average uptake of renal parenchyma, spleen and body background, as well as to compute the fraction of injected activity sequestered in tumour and excreted in urine. Uptake values were assessed for correlation with tumour sequestration, weight, lean body weight, body surface area and urinary excretion.

Results

There was a trend for tumour sequestration, body habitus and urinary excretion to inversely influence all healthy tissue uptake values. In particular, renal uptake, splenic intensity and background soft tissue activity were all significantly correlated to composite factors combining tumour sequestration with body habitus and renal excretion. When combined with body habitus index or a body habitus index and renal excretion, tumour sequestration was strongly and significantly correlated inversely with renal uptake.

Conclusion

Our results suggest that tumour sequestration of 68Ga-DOTA-octreotate is a major factor leading to a sink effect that decreases activity concentration in healthy organs such as the kidney. However, body habitus and renal function also influence tissue biodistribution, in a synergistic fashion. Compared with a fixed-dose peptide receptor radionuclide therapy protocol, an adjusted-dose regimen tailored to tumour burden, body habitus and renal function may allow greater radiation dose to individual lesions without substantially adding to toxicity in normal tissues.

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Acknowledgments

Jean-Mathieu Beauregard was supported by a fellowship bursary award from Laval University (Quebec, Canada). Professor Hicks is the recipient of a Victorian Government Translational Research Grant through the Victorian Cancer Agency to study genomic and dosimetric factors predictive of response of NET to PRRT. We would like to thank Dr. Oliver Neels and Mr. Peter Eu for preparation of GaTate and our nuclear medicine technologist team for their tireless work.

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Authors and Affiliations

  1. Centre for Cancer Imaging, Peter MacCallum Cancer Centre and University of Melbourne, Melbourne, Australia

    Jean-Mathieu Beauregard, Michael S. Hofman, Grace Kong & Rodney J. Hicks

  2. Molecular Imaging Research Group, Medical Imaging Department, Centre hospitalier universitaire de Québec and Laval University, 6 rue McMahon, Quebec City, QC, G1R 3S2, Canada

    Jean-Mathieu Beauregard

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  1. Jean-Mathieu Beauregard
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  2. Michael S. Hofman
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  3. Grace Kong
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  4. Rodney J. Hicks
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Correspondence to Jean-Mathieu Beauregard.

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Beauregard, JM., Hofman, M.S., Kong, G. et al. The tumour sink effect on the biodistribution of 68Ga-DOTA-octreotate: implications for peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging 39, 50–56 (2012). https://doi.org/10.1007/s00259-011-1937-3

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  • DOI: https://doi.org/10.1007/s00259-011-1937-3

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