Imaging nanoprobe for prediction of outcome of nanoparticle chemotherapy by using mammography

To prospectively predict the effectiveness of a clinically used nanochemotherapeutic agent by detecting and measuring the intratumoral uptake of an x-ray contrast agent nanoprobe by using digital mammography.

All animal procedures were approved by the institutional animal care and use committee. A long-circulating 100-nm-scale injectable liposomal probe encapsulating 155 mg/mL iodine was developed. Preliminary studies were performed to identify the agent dose that would result in adequate tumor enhancement without enhancement of the normal vasculature in rats. This dose was used to image a rat breast tumor (n = 14) intermittently for 3 days by using a digital mammography system; subsequently, the animals were treated with liposomal doxorubicin. The predictive capability of the probe was characterized by creating good- and bad-prognosis subgroups, on the basis of tumor enhancement found during imaging, and analyzing the tumor growth after treatment of the animals in these two subgroups.

A dose of 455 mg of iodine per kilogram of body weight was found to produce an undetectable signal from the blood while achieving enough intratumoral accumulation of the probe to produce adequate signal for detection. The good- and bad-prognosis subgroups demonstrated differential tumor growth rates (P < .003). An inverse linear relationship between the contrast enhancement rate constant during imaging and the tumor growth rate constant during treatment was found (slope = -0.576, R(2) = 0.838).

In this animal model, quantitative measurement of vascular permeability enabled prediction of therapeutic responsiveness of tumors to liposomal doxorubicin.