Dosimetry in radionuclide therapies with Y-90-conjugates: the IEO experience

The basis for a successful radionuclide therapy is a high and stable uptake of the radiopharmaceutical in the target tissue along with low activity co ncentration in other normal organs. The contribution of dosimetry in radion uclide therapy is to predict before the treatment the absorbed doses in tum or and normal organs, to identify the critical organs, to minimize any poss ible toxicity and to evaluate the maximum tolerated dose. We report our exp erience concerning pharmacokinetics and dosimetry of two Y-90-therapeutic p rotocols: 3-step pretargeting radioimmunotherapy (RIT) according to the bio tin-avidin system and receptor mediated radionuclide therapy with the somat ostatin analogue [DOTA-D-Phe(1)-Tyr(3)] octreotide named DOTATOC. For the d osimetric analysis, analogous approaches for the two radiolabeled compounds due to the similar pharmacokinetic characteristics were adopted; the MIRD formalism was applied, taking into account both the physical and the biolog ical characteristics of the radioconjugate and patients' metabolism. In ord er to determine biological clearance, serial blood samples and complete uri ne collection were obtained up to 48 hours after injection; to evaluate bio distribution, several whole body scans were acquired. Both therapies showed the advantageous characteristics of a fast blood clearance and a predomina ntly renal excretion of the radiopharmaceuticals thus lowering the irradiat ion of the total body. Although pharmacokinetic characteristis were similar , different critical organs were found for the two therapies; in particular , some considerations regarding red marrow, spleen and kidneys were require d. The results of our studies indicate that high activities of Y-90-biotin (3-step RIT) and Y-90-DOTATOC can be administered with acceptable radiation doses to normal organs.