Under the terms of the agreement, Dowpharma's MeO-DOTA bifunctional chelant will be utilised to attach the beta emitting radionuclide lutetium-177 as a payload to the 7E11-C5.3 (or 7E11) antibody, enabling targeted delivery of this cytotoxic agent. The company intends to develop the resulting innovative molecule for the treatment of various cancers, initially in prostate, that express the PSMA marker.
Chelation technology will specifically be used to attach a therapeutic radioisotope to the same murine monoclonal antibody utilised in Cytogen's Prostascint (capromab pendetide) molecular imaging agent.
This antibody is directed against an intracellular epitope of PSMA. The 7E11 antibody was excluded from the PSMA technology licensed to the PSMA Development Company LLC, the Company's joint venture for PSMA product development.
"This agreement marks a step in the development of our therapeutic franchise in oncology," said Michael Becker, Cytogen's president and chief executive officer.
Amongst Cytogen's products that treat cancer and related disorders is Quadramet, a targeted radiopharmaceutical that contains radioactive samarium combined with a bone-seeking agent that is used to target the drug to bone lesions, while minimising impact on normal cells.
Monoclonal antibodies labelled with radionuclides have previously proven successful for both the diagnosis and treatment of several tumours. However, its success is undermined by the ongoing problem regarding the stability of the chelating agents. The functions of the therapeutic radionuclides are wholly dependent on this stability to insure they do not separate from the monoclonal antibodies that target them to the tumours.
Cytogen's Prostascint molecular imaging agent is the first and only commercial product targeting PSMA. Prostascint consists of the 7E11 monoclonal antibody directed against PSMA that is linked to the radioisotope Indium-111.
Due to the selective expression of PSMA, the Prostascint molecular imaging procedure can detect the extent and spread of prostate cancer using a standard gamma camera. Clinical studies have demonstrated that overexpression of PSMA determined by immunohistochemical staining using 7E11 in primary prostate cancer not only correlates with other adverse traditional prognostic factors, but can independently predict disease recurrence.