Investigation of (90)Y-avidin for prostate cancer brachytherapy: a dosimetric model for a phase I-II clinical study.

Eur J Nucl Med Mol Imaging. 2013 Jul;40(7):1047-56. doi: 10.1007/s00259-013-2383-1
Botta F. Cremonesi M. Ferrari ME. Amato E. Guerriero F. Vavassori A. Sarnelli A. Severi S. Pedroli G. Paganelli G.

PURPOSEA novel method for prostate irradiation is investigated. Similarly to (125)I or (103)Pd seed brachytherapy, (90)Y-avidin could be injected via the perineum under ultrasound image guidance. This study inspects the theoretical feasibility with a dosimetric model based on Monte Carlo simulation.

METHODSA geometrical model of the prostate, urethra and rectum was designed. The linear-quadratic model was applied to convert (125)I absorbed dose prescription/constraints into (90)Y dose through biological effective dose (BED) calculation. The optimal (90)Y-avidin injection strategy for the present model was obtained. Dose distribution was calculated by Monte Carlo simulation (PENELOPE,GEANT4). Dose volume histograms (DVH) for the prostate, urethra and rectum were compared to typical DVHs of (125)I seed brachytherapy, used routinely in our institute.

RESULTSWith (90)Y-avidin, at least 95 % of the prostate must receive more than 70 Gy. The absorbed dose to 10 % of the urethra (D10%_urethra) and the maximum absorbed dose to the rectum (Dmax_rectum) must be lower than 122 Gy. For the present model, the optimum strategy consists in multiple injections of (90)Y-avidin 50 μl drops, for a total volume of 3.1 ml. The minimum activity to deliver the prescribed absorbed dose is 0.7 GBq, which also fully respects urethral and rectal constraints. The resulting dose map has a maximum in the central region with a sharp decrease towards the urethra and the prostate edge. Notably, D10%_urethra is 95 Gy and Dmax_rectum is below 2 Gy. Prostate absorbed dose is higher with (90)Y-avidin than (125)I seeds, although the total volume receiving the prescribed absorbed dose is 1-2 % lower. Urethral DVH strictly depends on the (90)Y distribution, to be optimized according to prostate shape; in our model, BED30%_urethra is 90 Gy with (90)Y-avidin, whereas for patients receiving (125)I seeds it ranges between 150 and 230 Gy. The rectal DVH is always more favourable with (90)Y.

CONCLUSIONThe methodology is theoretically feasible and can deliver an effective treatment in T1-T2 prostate cancer. Pharmacokinetic and biodistribution studies in prostate cancer patients are needed for validation.