evaluation of dna damage in a her2+ cell line induced by an auger-emitting immunoconjugate

introduction: auger electron based radioimmunotherapy (rit) using 111in-dota-trastuzumab (111in-dota-antiher2) feasibility was studied in vitro on a her2/neu positive cell line, skbr3. methods:111in-dota-antiher2 was prepared according to the optimized conditions followed by quality control tests including radiochemical purity; immunoreactivity). skbr3 as a her2/neu positive cell line was used to determine the degree of internalization and cell viability of 111in-dota-antiher2. for comet assay freshly cultivated skbr3 cells incubated with 111in-dota-antiher2 in 3.7 and 7.4 mbq doses at 37ºc for 24h. results:111in-dota-antiher2 (>95% radiochemical purity; >79% immunoreactivity) demonstrated significant internalization in skbr3 cells in 24 h. no significant cell viability difference observed for 111in-dota-antiher2 and 111in cation treatments. comet assay at 3.7 mbq demonstrated no significant dna damage, while at 7.4 mbq dose dna damage observed at least 16% more than control in-111 chloride after 24 h. conclusion: although the internalization of 111in-dota-antiher2 was approved in this study, however, lack of cell death and slight dna breakage for 111in-dota-antiher2 treatment suggests absence of nucleus entry which is essential for demonstration of dna damage according to auger electron range at cellular level.