The direct instillation of radiolabelled conjugates in the urinary bladder is a promising path for the treatment of bladder
carcinoma. The targeting of HER2/neu receptors expressed on the surface of many bladder
carcinoma cells shows potential to be developed as a therapeutic strategy, and patients identified with a high risk of progression may benefit from adjuvant targeted
radionuclide therapy. A phage-display selected Affibody molecule (Z(HER2:342)) which binds to HER2/neu with picomolar affinity, can be used for targeting HER2/neu-expressing bladder
carcinomas. A
DOTA-derivative of Z(HER2:342), designated as
DOTA-Z(HER2:342)-3, is considered as a suitable targeting agent for
therapy. The
DOTA chelator provides stable labelling with radiometals, and the low molecular weight (7.2 kDa) of the
DOTA-Z(HER2:342)-3 compound is expected to enable efficient
tumor penetration.
DOTA-Z(HER2:342)-3 was radiolabelled with 90Y and 177Lu in 1 M
ammonium acetate buffer, at pH 5.5, and in the presence of
ascorbic acid. Nearly quantitative labelling yields were achieved for both nuclides after 15 min of incubation at 60 degrees C. After chelation, the conjugates retained their capacity to specifically bind to HER2/neu-expressing SKOV-3 cells. The radiolabelled affibody conjugate (
DOTA-Z(HER2:342)-3) demonstrated high
antigen-binding capacity and good cellular retention. Biodistribution in normal mice demonstrated low uptake in all organs and tissues except for kidneys.