Imaging of human epidermal growth factor receptor type 2 expression with 18F-labeled affibody molecule Z HER2:2395 in a mouse model for ovarian cancer

Sandra Heskamp, Peter Laverman, Daniel Rosik, Frederic Boschetti, Winette T.A. Van Der Graaf, Wim J.G. Oyen, Hanneke W.M. Van Laarhoven, Vladimir Tolmachev, Otto C. Boerman

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

Affibody molecules are small (7 kDa) proteins with subnanomolar targeting affinity. Previous SPECT studies in xenografts have shown that the Affibody molecule 111In-DOTA-Z HER2:2395 can discriminate between high and low human epidermal growth factor receptor type 2 (HER2) - expressing tumors, indicating that radiolabeled Affibody molecules have potential for patient selection for HER2-targeted therapy. Compared with SPECT, PET with positron-emitting radionuclides, such as 18F, may improve imaging of HER2 expression because of higher sensitivity and improved quantification of PET. The aim of the present study was to determine whether the 18F-labeled NOTA-conjugated Affibody molecule Z HER2:2395 is a suitable agent for imaging of HER2 expression. The tumor-targeting properties of 18F-labeled Z HER2:2395 were compared with 111In- and 68Ga-labeled Z HER2:2395 in mice with HER2-expressing SK-OV-3 xenografts. Methods: Z HER2:2395 was conjugated with NOTA and radiolabeled with 18F, 68Ga, and 111In. Radiolabeling with 18F was based on the complexation of Al 18F by NOTA. The 50% inhibitory concentration values for NOTA-Z HER2:2395 labeled with 19F, 69Ga, and 115In were determined in a competitive cell-binding assay using SK-OV-3 cells. Mice bearing subcutaneous SK-OV-3 xenografts were injected intravenously with radiolabeled NOTA-Z HER2:2395. One and 4 h after injection, PET/CT or SPECT/CT images were acquired, and the biodistribution was determined by ex vivo measurement. Results: The 50% inhibitory concentration values for 19F-, 69Ga-, and 115In- NOTA-Z HER2:2395 were 5.0, 6.3, and 5.3 nM, respectively. One hour after injection, tumor uptake was 4.4 ± 0.8 percentage injected dose per gram (%ID/g), 5.6 ± 1.6%ID/g, and 7.1 ± 1.4%ID/g for 18F-, 68Ga-, and 111In-NOTA-Z HER2:2395, respectively, and the respective tumor-to-blood ratios were 7.4 ± 1.8, 8.0 ± 1.3, and 4.8 ± 1.3. Tumor uptake was specific, because uptake could be blocked efficiently by coinjection of an excess of unlabeled Z HER2:2395. PET/CT and SPECT/CT images clearly visualized HER2-expressing SK-OV-3 xenografts. Conclusion: This study showed that 18F-NOTA-Z HER2:2395 is a promising new imaging agent for HER2 expression in tumors. Affibody molecules were successfully labeled with 18F within 30 min, based on the complexation of Al 18F by NOTA. Further research is needed to determine whether this technique can be used for patient selection for HER2-targeted therapy.

Original languageEnglish
Pages (from-to)146-153
Number of pages8
JournalJournal of Nuclear Medicine
Volume53
Issue number1
DOIs
Publication statusPublished - 1 Jan 2012
Externally publishedYes

Keywords

  • F
  • Affibody molecule
  • HER2
  • Ovarian cancer
  • PET

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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