PRRT Dosimetry

Dosimetry and the dose-effect relations used in peptide receptor radionuclide therapy (PRRT) are predominately based on the experience from external beam radiation. In external beam radiotherapy, the recommended radiation toxicity threshold doses are based on empirical data resulting in consensus guidelines. In addition, there is also more than 60-year experience with 131I therapy (Iodine-131 sodium iodide) for the treatment of benign and malignant thyroid disorders. Dosimetry for PRRT is aimed at an optimal treatment with a maximal absorbed dose in the target tumor region together with acceptable absorbed doses in normal organs with physiological uptake like kidneys and bone marrow. Absorbed doses in the kidneys for PRRT are based on the MIRD method with adjustment for the patient's actual kidney mass. The dosimetry is based on quantization of the radioactivity uptake in organs and tumors at several time points. To compare absorbed doses by radionuclides with PRRT and external beam-derived threshold dose for renal toxicity, the linear quadratic model is of great value. This model links the biological effect (in this case late occurring renal disease) and the dose given, by compensating for the applied dose rate in a modified absorbed dose: the biologically effective dose (BED). The number of therapy cycles and the effective half-life with which the dose is build up are important features in the BED. Based on BED, a dose-effect model has been derived for renal toxicity after 90Y-DOTA-octreotide therapy, which corresponds well with the external beam experience given in 2Gy fractions. Fractionation of the PRRT therapy is essential to reduce the risk of renal toxicity. The dose to the bone marrow is based on the time-activity kinetics in blood and total body distribution. The dose limit for bone marrow is based on the limits set for 131I therapy, but the correlation between bone marrow absorbed dose and hematological toxicity has hardly been observed. The methods for determining the absorbed doses and BED in PRRT are explained, as well as methods to proof correlation with radiation-induced toxicity. Corrections for inhomogeneous dose distributions in the kidneys, depending on the β-particle range, are discussed.

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