UCSF

One of the challenges that physicians face is the uncertainty that their therapy of choice will be effective. A reason why therapeutic treatments often fall short in efficacy remains their limited presence and accumulation at the intended site of action. This challenge may be overcome by utilizing non-invasive molecular imaging. Attaching a radiolabel to the therapeutic, one may assess whether or not a drug accumulates at its target site, which may then allow one to more effectively predict whether patients may benefit from the treatment, thus offering patients a form of personalized medicine. Methods: Using a Zr-89 radionuclide and µPET/CT imaging technology, we assessed the pharmacokinetics (PK) of a novel chemotherapy tagged nanoparticle within various murine models engrafted with cell-line derived xenografts and patient-derived xenograft (PDX) tumors. Two other, non-therapeutic, versions of the nanoparticle were also radiolabeled and imaged so as to determine their potential as surrogate imaging probes for the therapeutic version. Tumor bearing mice were injected with 150 – 200 Ci of the Zr-89 labeled nanoparticles. Serial images were taken at 1, 24, 48, 72, 96, and 216 hours post-injection. Tumor and organ accumulation of the tracer were determined from the mouse µPET images. After the last imaging time-point, mice were euthanized and tumor, blood, and organs were weighted and counted. The percent injected dose per gram (%ID/g) of tissue was determined. Results: Nanoparticle radiolabeling was greater than 90% yield and 99% purity. µPET/CT time activity curves (TACs) showed very similar PK trends between the therapeutic and non-therapeutic nanoparticles. A steady accumulation followed by a plateauing of the nanoparticle concentrations within the growing tumors, as well as a clearance from all of the major organs (brain, heart, liver, and kidneys) was noted. Tumor maximum %ID/mL (5.81 – 18.14) occurred between the 72 and 96 hour time points, and ex vivo BioD experiments confirmed all of our in vivo PK findings (P > 0.05). Conclusion: Similar PK and BioD patterns between the therapeutic and non-therapeutic versions of the nanoparticle have validated that the imaging probes can in fact be used to predict the uptake and accumulation of the therapeutic nanoparticle.