LAUSR

Several FDA/EMA-approved nanomedicines have demonstrated improved pharmacokinetics and toxicity profiles compared to their conventional chemotherapeutic counterparts. The next step to increase therapeutic efficacy depends on tumor accumulation, which can be highly heterogeneous. A clinical tool for patient stratification is urgently awaited. Therefore, we radiolabeled a docetaxel-entrapping polymeric nanoparticle (89 Zr-CPC634) and performed positron emission tomography / computed tomography (PET/CT) imaging in seven patients with solid tumors with two different doses of CPC634: an on-treatment (containing 60 mg m-2 docetaxel) and a diagnostic (1-2 mg docetaxel) dose (NCT03712423). Pharmacokinetic half-life for 89 Zr-CPC634 was mean 97.0 ±14.4 hours on-treatment, and 62.4 ±12.9 hours for the diagnostic dose (p = 0.003). At these doses accumulation was observed in 46% and 41% of tumor lesions with a median accumulation in positive lesions 96 hours post-injection of 4.94 and 4.45%IA kg-1 (p = 0.91), respectively. In conclusion, PET/CT imaging with a diagnostic dose of 89 Zr-CPC634 accurately reflects on-treatment tumor accumulation and thus opens the possibility for patient stratification in cancer nanomedicine with polymeric nanoparticles. This article is protected by copyright. All rights reserved.