Tumour control probability derived from dose distribution in homogeneous and heterogeneous models: assuming similar pharmacokinetics, 125Sn–177Lu is superior to 90Y–177Lu in peptide receptor radiotherapy

Clinical trials on (177)Lu-(90)Y therapy used empirical activity ratios. Radionuclides (RN) with larger beta maximal range could favourably replace (90)Y. Our aim is to provide RN dose-deposition kernels and to compare the tumour control probability (TCP) of RN combinations. Dose kernels were derived by integration of the mono-energetic beta-ray dose distributions (computed using Monte Carlo) weighted by their respective beta spectrum. Nine homogeneous spherical tumours (1-25 mm in diameter) and four spherical tumours including a lattice of cold, but alive, spheres (1, 3, 5, 7 mm in diameter) were modelled. The TCP for (93)Y, (90)Y and (125)Sn in combination with (177)Lu in variable proportions (that kept constant the renal cortex biological effective dose) were derived by 3D dose kernel convolution. For a mean tumour-absorbed dose of 180 Gy, 2 mm homogeneous tumours and tumours including 3 mm diameter cold alive spheres were both well controlled (TCP > 0.9) using a 75-25% combination of (177)Lu and (90)Y activity. However, (125)Sn-(177)Lu achieved a significantly better result by controlling 1 mm-homogeneous tumour simultaneously with tumours including 5 mm diameter cold alive spheres. Clinical trials using RN combinations should use RN proportions tuned to the patient dosimetry. (125)Sn production and its coupling to somatostatin analogue appear feasible. Assuming similar pharmacokinetics (125)Sn is the best RN for combination with (177)Lu in peptide receptor radiotherapy justifying pharmacokinetics studies in rodent of (125)Sn-labelled somatostatin analogues.