PET‐CT Imaging of Polymeric Nanoparticle Tumor Accumulation in Patients

• Published in: Advanced materials (Weinheim) 2022-05, Vol.34 (21), p.e2201043-n/a
• Main Authors: Miedema, Iris H. C., Zwezerijnen, Gerben J. C., Huisman, Marc C., Doeleman, Ellen, Mathijssen, Ron H. J., Lammers, Twan, Hu, Qizhi, Dongen, Guus A. M. S., Rijcken, Cristianne J. F., Vugts, Danielle J., Menke‐van der Houven van Oordt, C. Willemien
• Format: Article
• Language: English
• Subjects: 89Zr; Accumulation; cancer; Computed tomography; docetaxel; Lesions; Materials science; Medical imaging; nanomedicines; Nanoparticles; PET/CT imaging; Pharmacology; polymeric nanoparticles; Positron emission; solid tumors; Tomography; Toxicity; Tumors; Zirconium isotopes
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202201043

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. In this study, the docetaxel‐entrapping polymeric nanoparticle CPC634 is radiolabeled with 89Zr and its potential as clinical tool for patients selection before starting treatment is evaluated. Positron emission tomography/computed tomography imaging of seven patients with solid tumors reveals that a low diagnostic dose of 89Zr‐CPC634 accurately reflects on‐treatment tumor accumulation which opens the possibility for patient stratification in cancer nanomedicine with polymeric nanoparticles.