89 Zr-Labeled High-Density Lipoprotein Nanoparticle PET Imaging Reveals Tumor Uptake in Patients with Esophageal Cancer

The Journal of Nuclear Medicine

article

Kang H. Zheng¹  Jeffrey Kroon²  Jasper Schoormans³  Oliver Gurney-Champion⁴  Sybren L. Meijer⁵  Suzanne S. Gisbertz⁶  Maarten C.C.M. Hulshof⁷  Danielle J. Vugts⁸  Guus A.M.S. van Dongen⁸  Bram F. Coolen³  Hein J. Verberne⁴  Aart J. Nederveen⁴  Erik S.G. Stroes¹  Hanneke W.M. van Laarhoven⁹ 

[1] Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam;Department of Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam;Department of Biomedical Engineering and Physics, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam;Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam;Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam;Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam;Department of Radiotherapy, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam;Department of Radiology and Nuclear Medicine, Amsterdam UMC, VU University;Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam

关键词: zirconium;    PET/CT;    high-density lipoprotein;    nanomedicine;    esophageal cancer;   

DOI  :  10.2967/jnumed.121.263330

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Nanomedicine holds promise for the delivery of therapeutic and imaging agents to improve cancer treatment outcomes. Preclinical studies have demonstrated that high-density lipoprotein (HDL) nanoparticles accumulate in tumor tissue on intravenous administration. Whether this HDL-based nanomedicine concept is feasible in patients is unexplored. Using a multimodal imaging approach, we aimed to assess tumor uptake of exogenously administered HDL nanoparticles in patients with esophageal cancer. Methods: The HDL mimetic CER-001 was radiolabeled using 89Zr to allow for PET/CT imaging. Patients with primary esophageal cancer staged T2 and above were recruited for serial 89Zr-HDL PET/CT imaging before starting chemoradiation therapy. In addition, patients underwent routine 18F-FDG PET/CT and 3-T MRI scanning (diffusion-weighted imaging/intravoxel incoherent motion imaging and dynamic contrast-enhanced MRI) to assess tumor glucose metabolism, tumor cellularity and microcirculation perfusion, and tumor vascular permeability. Tumor biopsies were analyzed for the expression of HDL scavenger receptor class B1 and macrophage marker CD68 using immunofluorescence staining. Results: Nine patients with adenocarcinoma or squamous cell carcinoma underwent all study procedures. After injection of 89Zr-HDL (39.2 ± 1.2 [mean ± SD] MBq), blood-pool SUVmean decreased over time (11.0 ± 1.7, 6.5 ± 0.6, and 3.3 ± 0.5 at 1, 24, and 72 h, respectively), whereas liver and spleen SUVmean remained relatively constant (4.1 ± 0.6, 4.0 ± 0.8, and 4.3 ± 0.8 at 1, 24, and 72 h, respectively, for the liver; 4.1 ± 0.3, 3.4 ± 0.3, and 3.1 ± 0.4 at 1, 24, and 72 h, respectively, for the spleen) and kidney SUVmean markedly increased over time (4.1 ± 0.9, 9.3 ± 1.4, and 9.6 ± 2.0 at 1, 24, and 72 h, respectively). Tumor uptake (SUVpeak) increased over time (3.5 ± 1.1 and 5.5 ± 2.1 at 1 and 24 h, respectively [P = 0.016]; 5.7 ± 1.4 at 72 h [P = 0.001]). The effective dose of 89Zr-HDL was 0.523 ± 0.040 mSv/MBq. No adverse events were observed after the administration of 89Zr-HDL. PET/CT and 3-T MRI measures of tumor glucose metabolism, tumor cellularity and microcirculation perfusion, and tumor vascular permeability did not correlate with tumor uptake of 89Zr-HDL, suggesting that a specific mechanism mediated the accumulation of 89Zr-HDL. Immunofluorescence staining of clinical biopsies demonstrated scavenger receptor class B1 and CD68 positivity in tumor tissue, establishing a potential cellular mechanism of action. Conclusion: To our knowledge, this was the first 89Zr-HDL study in human oncology. 89Zr-HDL PET/CT imaging demonstrated that intravenously administered HDL nanoparticles accumulated in tumors of patients with esophageal cancer. The administration of 89Zr-HDL was safe. These findings may support the development of HDL nanoparticles as a clinical delivery platform for drug agents. 89Zr-HDL imaging may guide drug development and serve as a biomarker for individualized therapy.

【 授权许可】

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