Journal
NUCLEAR MEDICINE COMMUNICATIONS
Volume 35, Issue 12, Pages 1284-1290Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MNM.0000000000000199
Keywords
APOMAB; La/SSB antigen; Lewis lung carcinoma; radioimmunotherapy; thorium-227; alpha-therapy
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Resistance to conventional cancer treatments is a major problem associated with solid tumours. Tumour hypoxia is associated with a poor prognosis and with poor treatment outcomes; therefore, there is a need for treatments that can kill hypoxic tumour cells. One potential option is targeted -radioimmunotherapy, as -particles can directly kill hypoxic tumour cells. The murine monoclonal antibody DAB4 (APOMAB), which binds dead tumour cells after DNA-damaging treatment, was conjugated and radiolabelled with the -particle-emitting radionuclide thorium-227 (Th-227). Mice bearing Lewis lung tumours were administered Th-227-DAB4 alone or after chemotherapy and the tissue biodistribution of the radioimmunoconjugate was examined, as was the effect of these treatments on tumour growth and survival. Th-227-DAB4 accumulated in the tumour particularly after chemotherapy, whereas the distribution in healthy tissues did not change. Th-227-DAB4 as a monotherapy increased survival, with more pronounced responses observed when given after chemotherapy. We have shown that targeted -therapy of necrotic tumour cells with Th-227-DAB4 had significant and surprising antitumour activity as it would occur only through a cross-fire effect.
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