90Yttrium-AABD targeted to the humanized PET reporter gene hDAbR1 expressed on human ovarian cancer cell membrane inhibits tumor growth in vivo

Objectives We have developed a humanized version of DAbR1 (hDAbR1), an engineered antibody fragment that can be expressed on cell membrane for PET imaging. We investigated its function for PET imaging and used 90Y-AABD for target specific radiotherapy of human ovarian cancer.

Methods DAbR1, consists of anti-DOTA antibody 2D12.5 fused to the CD4 transmembrane domain. The corresponding reporter probe is Y[asterisk]-AABD, a DOTA complex that irreversibly binds to a cysteine residue in the 2D12.5 antibody. 2D12.5 is a murine antibody. In the humanized version of DAbR1, 2D12.5 light and heavy chains DNA sequence in frame regions have been replaced with human sequences, while the complementarity determining regions (CDR) regions remained the same as original. So it does not interfere with the covalent bond with the DOTA compound AABD. Human ovarian cancer hey cells that stably express hDAbR1 were subcutaneously injected into NSG mice.

Results PET imaging with 86Y-AABD demonstrated intense tumor uptake at 20 h of probe injection (20.7 ±1.9%ID/g). Treatment with single dose of 200 μCi of 90Y-AABD markedly delays tumor growth and reduces tumor 18F-FDG uptakes.

Conclusions hDAbR1/90Y-AABD system can serve as an ideal tool for target specific radiotherapy of human cancer. $$graphic_C9496ABE-8A6F-41D8-8DFB-D9CE6EABB8B5$$