Efficient [18F]AlF Radiolabeling of ZHER3:8698 Affibody Molecule for Imaging of HER3 Positive Tumors

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• 作者：Chiara Da Pieve ; Louis Allott ; Carlos D. Martins ; Andrew Vardon ; Daniela M. Ciobota ; Gabriela Kramer-Marek ; Graham Smith
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：August 17, 2016
• 年：2016
• 卷：27
• 期：8
• 页码：1839-1849
• 全文大小：508K
• 年卷期：0
• ISSN：1520-4812

文摘

The human epidermal growth factor receptor 3 (HER3) is overexpressed in several cancers, being linked to a more resistant phenotype and hence leading to poor patient prognosis. Imaging HER3 is challenging owing to the modest receptor number (<50000 receptors/cell) in overexpressing cancer cells. Therefore, to image HER3 in vivo, high target affinity PET probes need to be developed. This work describes two different [¹⁸F]AlF radiolabeling strategies of the Z_HER3:8698 affibody molecule specifically targeting HER3. The one-pot radiolabeling of Z_HER3:8698 performed at 100 °C and using 1,4,7-triazanonane-1,4,7-triacetate (NOTA) as chelator resulted in radiolabeled products with variable purity attributed to radioconjugate thermolysis. An alternative approach based on the inverse electron demand Diels–Alder (IEDDA) reaction between a novel tetrazine functionalized 1,4,7-triazacyclononane-1,4-diacetate (NODA) chelator and the trans-cyclooctene (TCO) functionalized affibody molecule was also investigated. This method enabled the radiolabeling of the protein at room temperature. The [¹⁸F]AlF-NOTA-Z_HER3:8698 and [¹⁸F]AlF-NODA-Z_HER3:8698 conjugates showed a specific uptake at 1 h after injection in high HER3-expressing MCF-7 tumors of 4.36 ± 0.92% ID/g and 4.96 ± 0.65% ID/g, respectively. The current results are encouraging for further investigation of [¹⁸F]AlF-NOTA-Z_HER3:8698 as a HER3 imaging agent.