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  3. PET-CT Imaging of Polymeric Nanoparticle Tumor Accumulation in Patients

PET-CT Imaging of Polymeric Nanoparticle Tumor Accumulation in Patients

  • Adv Mater. 2022 May;34(21):e2201043. doi: 10.1002/adma.202201043.
Iris H C Miedema 1 2,  Gerben J C Zwezerijnen 2 3,  Marc C Huisman 2 3,  Ellen Doeleman 1 2,  Ron H J Mathijssen 4,  Twan Lammers 5,  Qizhi Hu 6,  Guus A M S van Dongen 2 3,  Cristianne J F Rijcken 6,  Danielle J Vugts 2 3,  C Willemien Menke-van der Houven van Oordt 1 2
Affiliations

Affiliations

  • 1 Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Medical Oncology, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
  • 2 Cancer Center Amsterdam, Imaging and Biomarkers, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
  • 3 Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Radiology and Nuclear Medicine, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
  • 4 Erasmus University Medical Center, Erasmus University, Erasmus MC Cancer Institute, Department of Medical Oncology, Doctor Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands.
  • 5 Institute for Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, RWTH - Aachen University, Templergraben 55, 52062, Aachen, Germany.
  • 6 Cristal Therapeutics, Oxfordlaan 55, Maastricht, 6229 EV, The Netherlands.
PMID: 35427430 DOI: 10.1002/adma.202201043
Abstract

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 (89 Zr-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 89 Zr-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 89 Zr-CPC634 accurately reflects on-treatment tumor accumulation and thus opens the possibility for patient stratification in Cancer nanomedicine with polymeric nanoparticles.

Keywords

89Zr; PET/CT imaging; cancer; docetaxel; nanomedicines; polymeric nanoparticles; solid tumors.

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