Abstract
Nanobodies are the smallest fully functional antigen-binding
antibody fragments possessing ideal properties as probes for
molecular imaging. In this study we labeled the anti–human
epidermal growth factor receptor type 2 (HER2) Nanobody with
68Ga via a 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)
derivative and assessed its use for HER2 iPET imaging. Methods:
The 2Rs15dHis6 Nanobody and the lead optimized
current-good-manufacturing-practice grade analog 2Rs15d
were conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7-
triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) to enable
fast and efficient 68Ga labeling. Biodistribution and PET/CT
studies were performed on HER2-positive and -negative tumor
xenografts. The effect of injected mass on biodistribution was
evaluated. The biodistribution data were extrapolated to calculate
radiation dose estimates for the adult female using OLINDA
software. A single-dose extended-toxicity study for NOTA-
2Rs15d was performed on healthy mice up to a dose of
10 mg/kg.
Details
Original language | English |
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Pages (from-to) | 776-784 |
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Journal | Journal of Nuclear Medicine |
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Volume | 54 |
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Issue number | 5 |
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DOIs | |
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Publication status | Published - 13 May 2013 |
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