Abstract A229: Novel in vivo imaging of chemotherapy-induced gonadotoxicity

Abstract

Abstract Introduction: Advances in cancer therapy have improved the long-term survival of cancer patients who may then face infertility and premature gonadal failure due to chemotherapy. It has been demonstrated that the chemotherapeutic agent doxorubicin (DXR) induces apoptosis in germ cells, though its role in inflicting potential gonadal failure remains obscure. We had previously shown ovarian damage in mice following DXR treatment, manifested by reduced ovarian size and weight and by apoptosis. We aimed at establishing a real-time in vivo molecular imaging platform in mice designated to evaluate chemotherapy-induced toxicity and to assess potential vascular insult in both ovaries and testes. Methods: The volume of both ovaries and testes was measured in vivo by ultrasound biomicroscopy (Vevo2100) and by high resolution MRI, over a period of one month after adminstration of 10mg/kg intraperitoneal DXR. Ovaries were imaged by ultrasound using microbubbles as a contrast agent for evaluating the effect of DXR on ovarian blood flow. Results: We have established a platform of visualizing the gonads by innovative high resolution ultrasound biomicroscopy and MRI that enabled in vivo detection of chemotherapy-induced effects in the same individuals over time. We observed a constant, significant reduction in gonadal volume, evident by both MRI and ultrasound. The ovary volume was reduced to 52% (N=10, p<0.05) of baseline values over one month. A similar trend was observed in the testes (reduced to 38% of baseline values over one month; N=6 p<0.05)). The use of bubbles as contrast media depicted a 30% reduction in ovarian blood flow already 15 min after DXR administration. Conclusions: Using high resolution, state of the art imaging modules enabled us to trace chemotherapy-induce gonadotoxicity by in vivo imaging of the same individuals throughout an extended period of time. The acute reduction of ovarian blood flow following chemotherapy treatment may suggest a role for vascular injury in inflicting ovarian damage. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A229.