177Lu-DO3A-HSA-Z EGFR:1907: Characterization as a potential radiopharmaceutical for radionuclide therapy of EGFR-expressing head and neck carcinomas

Susan Hoppmann, Shibo Qi, Zheng Miao, Hongguang Liu, Han Jiang, Cathy S. Cutler, Ande Bao, Zhen Cheng

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Epidermal growth factor receptor 1 (EGFR) is an attractive target for radionuclide therapy of head and neck carcinomas. Affibody molecules against EGFR (Z EGFR) show excellent tumor localizations in imaging studies. However, one major drawback is that radiometal-labeled Affibody molecules display extremely high uptakes in the radiosensitive kidneys which may impact their use as radiotherapeutic agents. The purpose of this study is to further explore whether radiometal-labeled human serum albumin (HSA)-Z EFGR bioconjugates display desirable profiles for the use in radionuclide therapy of EGFR-positive head and neck carcinomas. The Z EFGR analog, Ac-Cys-Z EGFR:1907, was site-specifically conjugated with HSA. The resulting bioconjugate 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A)-HSA-Z EGFR:1907 was then radiolabeled with either 64Cu or 177Lu and subjected to in vitro cell uptake and internalization studies using the human oral squamous carcinoma cell line SAS. Positron emission tomography (PET), single photon emission computed tomography (SPECT), and biodistribution studies were conducted using SAS-tumor-bearing mice. Cell studies revealed a high (8.43 ± 0.55 % at 4 h) and specific (0.95 ± 0.09 % at 4 h) uptake of 177Lu-DO3A-HSA-Z EGFR:1907 as determined by blocking with nonradioactive Z EGFR:1907. The internalization of 177Lu-DO3A-HSA-Z EGFR:1907 was verified in vitro and found to be significantly higher than that of 177Lu-labeled Z EFGR at 2-24 h of incubation. PET and SPECT studies showed good tumor imaging contrasts. The biodistribution of 177Lu-DO3A-HSA-Z EGFR:1907 in SAS-tumor-bearing mice displayed high tumor uptake (5.1 ± 0.44 % ID/g) and liver uptake (31.5 ± 7.66 % ID/g) and moderate kidney uptake (8.5 ± 1.08 % ID/g) at 72 h after injection. 177Lu-DO3A-HSA-Z EGFR:1907 shows promising in vivo profiles and may be a potential radiopharmaceutical for radionuclide therapy of EGFR-expressing head and neck carcinomas.

Original languageEnglish (US)
Pages (from-to)709-718
Number of pages10
JournalJournal of Biological Inorganic Chemistry
Volume17
Issue number5
DOIs
StatePublished - Jun 1 2012

Keywords

  • Lu
  • Affibody
  • Epidermal growth factor receptor
  • Human serum albumin
  • Radionuclide therapy

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

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