Development of 170Tm‐DOTA‐cetuximab for radioimmunotherapy

Abstract

Thulium‐170 [T1/2 = 128.4 days, Eβ(max) = 968 keV, Eγ = 84 keV (3.26%)] has radionuclidic properties suitable for use in therapy. 170Tm can be produced by a relatively feasible route involving thermal neutron bombardment on natural Tm(NO3)3 (100% 169Tm) in medium flux research reactors. The combination of beta‐particle emission of Tm‐170 with therapeutic properties of C225 monoclonal antibody (cetuximab) as well as optimization studies for future Tm‐167 labeling was targeted in this study. Conjugated cetuximab was obtained by the addition of 0.5 ml of a cetuximab pharmaceutical solution (1 mg, in phosphate buffer, pH 7.8) to a glass tube pre‐coated with in situ prepared 1,4,7,10‐tetraazacyclododecane‐N,N,N,N‐tetraacetic acid mono‐(N‐hydroxysuccinimidyl) ester (DOTA‐NHS) (~5 mg) at 25°C. Cetuximab was labeled with 170Tm‐Thulium chloride (100 MBq) after conjugation with DOTA‐NHS in 2–3 h (radiochemical purity >99%, instant thin‐layer chromatography, specific activity = 77–385 TBq/mmol). Biodistribution studies in wild‐type rats for free Tm‐170 and the radioimmunoconjugate were performed to determine the distribution up to 72 h. A comparative time‐frame study was performed for critical organs for both radiochemical species. The major organs of accumulation were shown to be the lung, liver, and spleen, respectively. Copyright © 2012 John Wiley & Sons, Ltd.