Translation of dosimetric results of preclinical radionuclide therapy to clinical situations: influence of photon irradiation.

The radionuclide evaluation for therapy starts with preclinical studies in, for example, mice and rats, and various radionuclides have shown promising results. However, many radionuclides emit photons that will irradiate normal tissues. The risk of normal tissue toxicity in patients (e.g., bone marrow suppression) may be underestimated when relying on preclinical results. To illustrate the influence of photons in preclinical and clinical trials, the ratio between the tumor-to-normal tissue absorbed-dose rate ratio (TND) was calculated for humans, rats, and mice for 111In, 125I, 67Ga, 90Y, 131I, and 177Lu. The normal tissues were simulated by 70-kg, 300-g, and 20-g ellipsoids for humans, rats, and mice, respectively. It was assumed that the radionuclides were uniformly distributed, and that the activity concentration was 25 times higher in the tumor than in the normal tissue. There were only small differences between the TND values for the different species for 90Y and 177Lu. 131I showed similar TND values for rats and mice, whereas they were lower for humans. For 111In, 125I, and 67Ga, however, there were large differences between the different species. The influence of photons may thus be much lower in preclinical studies than in clinical situations. Therefore, translations of absorbed doses from animals to humans must be performed with caution.