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Radiation Dose Distribution in Human Kidneys by Octreotides in Peptide Receptor Radionuclide Therapy

¹ Research and Development, Mallinckrodt Medical BV, Tyco Healthcare, Petten, The Netherlands; and ² Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

Correspondence: For correspondence or reprints contact: Mark Konijnenberg, PhD, Mallinckrodt Medical BV, Postbus 3, 1755ZG Petten, The Netherlands. E-mail: Mark.Konijnenberg{at}emea.tycohealthcare.com

Ex vivo autoradiographs of healthy kidney tissue from patients who received ¹¹¹In-DTPA-octreotide (DTPA is diethylenetriaminepentaacetic acid) before nephrectomy showed very heterogeneous radioactivity patterns in the kidneys. The consequences of the reported inhomogeneities have been evaluated for radionuclide therapy with ⁹⁰Y- DOTA-Tyr³-octreotide (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid), ¹⁷⁷Lu-DOTA-Tyr³-octreotate, and ¹¹¹In-DTPA-octreotide by calculating dose distributions and dose–volume histograms (DVHs) for the kidneys. Methods: Monte Carlo radiation transport calculations were performed by using the MCNP code version 5. The autoradiography data were used in a 2-dimensional model of the kidney tissue sections. A voxel structure inside the MIRD Pamphlet 19 multiregion kidney model was developed to generate a 3-dimensional representation of the autoradiographs. Dose distributions were calculated for the ß-emitter ⁹⁰Y, the low-energy electron and -emitter ¹¹¹In, and the ß- and -emitter ¹⁷⁷Lu. Isodose curves were generated for the 2-dimensional kidney sections and DVHs for the 3-dimensional kidney model. Results: The isodose curves for the high-energy ß-emitter ⁹⁰Y did not show a sign of the inhomogeneous activity distribution, apart from the cortex–medulla boundaries. Both ¹¹¹In and ¹⁷⁷Lu isodose curves follow the autoradiographic activity distribution exactly. The 2 -rays from ¹¹¹In give higher doses to the low-radioactivity regions in the kidney sections. The DVHs show that the inhomogeneous activity distribution creates considerable volumes within the kidney and within the cortex with lower doses than the average kidney dose, together with volumes receiving much higher doses. This effect is most profound for ¹⁷⁷Lu, but also ¹¹¹In shows this heterogeneity in the dose distribution. Conclusion: Kidney dosimetry for radionuclide therapy can be based on average MIRD-based dose models for high-energy ß-emitters (such as ⁹⁰Y). In contrast, low-energy ß-emitters (such as ¹⁷⁷Lu) and Auger-electron–emitting radionuclides (such as ¹¹¹In) produce dose distributions in the kidneys that are very dependent on the activity distribution pattern in the kidney or renal cortex. Complication probability models for renal tissue damage after radionuclide therapy with these latter nuclides need to be developed, as the existing models based on average dose to the kidney or cortex from external beam therapy experience are most probably not valid.

Key Words: kidney dosimetry • dose volume histogram • ⁹⁰Y-DOTA-octreotide • ¹¹¹In-DTPA-octreotide • ¹⁷⁷Lu-DOTA-octreotate • radionuclide therapy

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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