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, a docetaxel‐entrapping polymeric nanoparticle (89Zr‐CPC634) is radiolabeled, and positron emission tomography/computed tomography (PET/CT) imaging is performed 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 89Zr‐CPC634 is mean 97.0 ± 14.4 h on‐treatment, and 62.4 ± 12.9 h for the diagnostic dose (p = 0.003). At these doses accumulation is observed in 46% and 41% of tumor lesions with a median accumulation in positive lesions 96 h 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 89Zr‐CPC634 accurately reflects on‐treatment tumor accumulation and thus opens the possibility for patient stratification in cancer nanomedicine with polymeric nanoparticles.

We report the development and validation of a 12 parameter immunofluorescence flow cytometry method for the sensitive determination of cell concentrations, their expression of PD-1, and PD-1 receptor occupancy. Cell subsets include CD4 + and CD8 + -Tcells, B-cells, natural killer cells, classical-, intermediate-and non-classical monocytes, and myeloid-and plasmacytoid dendritic cells. Cells were isolated from peripheral blood by density gradient centrifugation. The validation parameters included specificity, linearity, limit of quantification, precision, biological within-and between subject variations. The lower limit of quantification was 5.0% of PD-1 + cells. Samples were stable for at least 153 days of storage at −80 C. The clinical applicability of the method was demonstrated in 11 advanced cancer patients by the successful determination of immune cell concentrations, relative number of PD-1 + immune cells, and number of PD-1 molecules per immune cell. Shortly after infusion of nivolumab, receptor occupancy on CD8 + -T-cells was 98%. Similar values were found predose cycle 2, suggesting receptor occupancy remained high throughout the entire cycle.

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