Evaluation of 99mTc-ZIGF1R:4551-GGGC affibody molecule, a new probe for imaging of insulin-like growth factor type 1 receptor expression

Bogdan Mitran, Mohamed Altai, Camilla Hofström, Hadis Honarvar, Mattias Sandström, Anna Orlova, Vladimir Tolmachev, Torbjörn Gräslund

Результат исследований: Материалы для журналаСтатьярецензирование

18 Цитирования (Scopus)


Overexpression of insulin-like growth factor-1 receptor (IGF-1R) in several cancers is associated with resistance to therapy. Radionuclide molecular imaging of IGF-1R expression in tumors may help in selecting the patients that will potentially respond to IGF-1R-targeted therapy. Affibody molecules are small (7 kDa) non-immunoglobulin-based scaffold proteins that are well-suited probes for radionuclide imaging. The aim of this study was the evaluation of an anti-IGF-1R affibody molecule labeled with technetium-99m using cysteine-containing peptide-based chelator GGGC at C-terminus. ZIGF1R:4551-GGGC was efficiently and stably labeled with technetium-99m (radiochemical yield 97 ± 3 %). 99mTc-ZIGF1R:4551-GGGC demonstrated specific binding to IGF-1R-expressing DU-145 (prostate cancer) and MCF-7 (breast cancer) cell lines and slow internalization in vitro. The tumor-targeting properties were studied in BALB/c nu/nu mice bearing DU-145 and MCF-7 xenografts. [99mTc(CO)3]+-(HE)3-ZIGF1R:4551 was used for comparison. The biodistribution study demonstrated high tumor-to-blood ratios (6.2 ± 0.9 and 6.9 ± 1.0, for DU-145 and MCF-7, respectively, at 4 h after injection). Renal radioactivity concentration was 16-fold lower for 99mTc-ZIGF1R:4551-GGGC than for [99mTc(CO)3]+-(HE)3-ZIGF1R:4551 at 4 h after injection. However, the liver uptake of 99mTc-ZIGF1R:4551-GGGC was 1.2- to 2-fold higher in comparison with [99mTc(CO)3]+-(HE)3-ZIGF1R:4551. A possible reason for the elevated hepatic uptake of 99mTc-ZIGF1R:4551-GGGC is a high lipophilicity of amino acids in the binding site of ZIGF1R:4551, which is not compensated in 99mTc-ZIGF1R:4551-GGGC. In conclusion, 99mTc-ZIGF1R:4551-GGGC can visualize the IGF-1R expression in human tumor xenografts and provides low retention of radioactivity in kidneys. Further development of this imaging agent should include molecular design aimed at reducing the hepatic uptake.

Язык оригиналаАнглийский
Страницы (с-по)303-315
Число страниц13
ЖурналAmino Acids
Номер выпуска2
СостояниеОпубликовано - фев 2015
Опубликовано для внешнего пользованияДа

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

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