Subscribe to RSS
DOI: 10.1055/s-0040-1708375
A mathematical model to improve Tumour Anti-Vascular Alpha Therapy (TAVAT) with 212 Pb-labelled monoclonal antibodies
Publication History
Publication Date:
08 April 2020 (online)
Ziel/Aim Tumour anti–vascular alpha therapy (TAVAT) is an attractive approach in the treatment of solid tumours by targeting tumour angiogenesis. A mathematical model was developed to describe the pharmacokinetics and the absorbed doses of Pb-212-labelled monoclonal antibodies (mAbs) targeting tumour angiogenesis.
Methodik/Methods A compartmental model for tumour neovasculature, plasma, the remainder of body (representing the volume of distribution of free radionuclides) and kidneys as organs at risk was developed and implemented (parameter values from the literature) in the modelling software SAAMII. Excretion of free Bi-212 was included in a physiological kidney model1. Kidney parameter values were estimated in a developed excretion model for stable Bi. Absorbed doses in the investigated spaces were calculated at various injected amounts and activities for all emitted radiations. The absorbed doses in plasma and kidneys vasculature for different antigen densities were calculated for a fixed dose of 30 Gy in tumour neovasculature and for different molar activities.
Ergebnisse/Results The simulations show that the prescribed dose in tumour neovasculature of 30 Gy was achieved in the case of 5 nmol/l of antigen density by injecting 0.049 GBq of Pb-212-labelled mAbs with a molar activity of 10.9 GBq/nmol; the absorbed doses in kidneys vasculature and plasma were 1.03 and 1.04 Gy, respectively. The rel. contributions of alpha emissions of Bi-212 and Po-212 to the total absorbed dose were 22 % and 56 %, respectively. The total contribution of beta emissions to the absorbed dose was 22 %.
Schlussfolgerungen/Conclusions The presented mathematical model of Pb-212-labelled mAbs allows the simulation of the pharmacokinetics of bound and free radiopharmaceuticals and released radionuclides in the body. Dosimetry calculations for non-target tissues allow estimating the therapeutic efficacy and safety of TAVAT.