Evaluation of Tc-99m-Z(IGF1R:4551)-GGGC affibody molecule, a new probe for imaging of insulin-like growth factor type 1 receptor expression

• 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. Z(IGF1R:4551)-GGGC was efficiently and stably labeled with technetium-99m (radiochemical yield 97 +/- A 3 %). Tc-99m-Z(IGF1R: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. [Tc-99m(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) was used for comparison. The biodistribution study demonstrated high tumor-to-blood ratios (6.2 +/- A 0.9 and 6.9 +/- A 1.0, for DU-145 and MCF-7, respectively, at 4 h after injection). Renal radioactivity concentration was 16-fold lower for Tc-99m-Z(IGF1R:4551)-GGGC than for [Tc-99m(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) at 4 h after injection. However, the liver uptake of Tc-99m-Z(IGF1R:4551)-GGGC was 1.2- to 2-fold higher in comparison with [Tc-99m(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551). A possible reason for the elevated hepatic uptake of Tc-99m-Z(IGF1R:4551)-GGGC is a high lipophilicity of amino acids in the binding site of Z(IGF1R:4551), which is not compensated in Tc-99m-Z(IGF1R:4551)-GGGC. In conclusion, Tc-99m-Z(IGF1R: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.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology (hsv//eng)

Nyckelord

Affibody molecule

IGF-1R

Peptide-based chelator

Tc-99m

Biodistribution

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