Abstract. The size of affibody molecules makes them suitable as targeting agents for targeted radiotherapy with the ·-emitter 211 At, since their biokinetic properties match the short physical half-live of 211 At. In this study, the potential for this approach was investigated in vivo. Two different HER-2 binding affibody molecules were radiolabeled with 211 At using both the linker PAB (N-succinimidyl-para-astatobenzoate) and a decaborate-based linker, and the biodistribution in tumorbearing nude mice was investigated. The influence of L-lysine and Na-thiocyanate on the 211 At uptake in normal tissues was also studied. Based on the biokinetic information obtained, the absorbed dose was calculated for different organs. Compared with a previous biodistribution with 125 I, the 211 At biodistribution using the PAB linker showed higher uptake in lungs, stomach, thyroid and salivary glands, indicating release of free 211 At. When the decaborate-based linker was used, the uptake in those organs was decreased, but instead, high uptake in kidneys and liver was found. The uptake, when using the PAB linker, could be significantly reduced in some organs by the use of L-lysine and/or Na-thiocyanate. In conclusion, affibody molecules have suitable blood-kinetics for targeted radionuclide therapy with 211 At. However, the labeling chemistry affects the distribution in normal organs to a high degree and needs to be improved to allow clinical use.
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