Dosimetry for Peptide Receptor Radionuclide Therapy
For over more than a decade, the progressive evolution of Peptide Receptor Radionuclide Therapy (PRRT) for the treatment of tumors expressing somatostatin receptors has been constantly challenging—and challenged by—dosimetry. The improvements reached in the therapeutical applications of 90Y- and 177Lu- radiolabeled peptides are considerable, and new perspectives are on the way. These results have been possible due to the special complicity among various disciplines having the optimization of PPRT as common goal, with dosimetry at center stage. Its role has been precious for an attentive radionuclide and radiopeptide selection, for the upgrading of the protocol rationales and therapy schemes, for toxicity prevention. Especially, the high irradiation of the kidneys, the low but inevitable dose to the bone marrow, as well as the large dose variability of non-target organs and tumors, which emerged from the clinical trials, have been sustaining the need of reliable dosimetry. Although dose estimates still do not reach the finest accuracy, relevant progress in dosimetric methods is being obtained. Their application to this quite early therapy—avid of information—addresses the examination of the risk-benefit balance, toward the approach of a tailored treatment planning. The availability of dosimetric data has allowed to evaluate the efficacy of renal protective agents and to validate radiobiological models for dose-toxicity correlations on kidneys. The probability of renal impairment being predictable, the injected activity can be fitted to any patient for a safe kidney dose.
KeywordsExternal Beam Radiation Therapy Peptide Receptor Radionuclide Therapy Dose Volume Histogram Biological Effective Dose Equivalent Uniform Dose
The authors wish to thank Mrs Deborah Console for editing the manuscript, Dr. Stefano Papi for useful discussions on radiochemical analyses, and the colleagues of the Medical Physics and Nuclear Medicine Divisions for their support.
- Barone R, Borson-Chazot F, Valkema R et al. (2005) Patient-specific dosimetry in predicting renal toxicity with 90Y-DOTATOC: relevance of kidney volume and dose rate in finding a dose–effect relationship. J Nucl Med 46 (supp):99S–106SGoogle Scholar
- Botta F, Valente M, Di Dia A et al (2008) 3D absorbed dose distribution inside and outside 90Y, 177Lu and 131I sources of spherical shape by Monte Carlo simulation with the PENELOPE algorithm [abstract]. Eur J Nucl Med Mol Imaging 35:S201Google Scholar
- Cassady JR (1995) Clinical radiation nephropathy. Int J Radiat Oncol Biol Phys 30, 31(5):1249–1256Google Scholar
- Cremonesi M, Bodei L, Botta F et al (2009) Time interval, number of cycles and radionuclide choice in PRRT (Peptide Receptor Radionuclide Therapy): radiobiological considerations to guide therapy planning [abstract]. Eur J Nucl Med Mol Imaging 36:S194Google Scholar
- Garkavij M, Nickel M, Sjögreen-Gleisner K et al. (2010) (177)Lu-[DOTA0,Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: analysis of dosimetry with impact on future therapeutic strategy. Cancer 16(S4):1084–1092Google Scholar
- International Commission on Radiological Protection (1979) Limits for intakes of radionuclides by workers. ICRP Publication 30. Pergamon Press, New YorkGoogle Scholar
- Kunikowska J, Krolicki L, Hubalewska-Dydejczyk A et al (2009) Comparison between clinical results of PRRT with 90Y-DOTATATE and 90Y/177Lu-DOTATATE [abstract]. Eur J Nucl Med Mol Imaging 36:S194Google Scholar
- Loevinger R, Budinger T, Watson EE (1991) MIRD Primer for absorbed dose calculations. The Society of Nuclear Medicine, New YorkGoogle Scholar
- Siegel JA, Thomas SR, Stubbs JB et al (1999) Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. MIRD Pamphlet No.16. J Nucl Med 40:S37–S61Google Scholar
- Svensson J, Molne J, Schmitt A et al (2009) Equal mean absorbed kidney dose from 177Lu-DOTATATE will generate different kidney toxicity profiles in nude mice. Eur J Nucl Med Mol Imaging 36 (supp):S206Google Scholar
- Walrand S, Flux GD, Konijnenberg MW et al (2011) Dosimetry of yttrium-labelled radiopharmaceuticals for internal therapy: 86Y or 90Y imaging? Eur J Nucl Med Mol Imaging 38(Suppl 1):S57–S68Google Scholar