Imaging of HER3-expressing xenografts in mice using a 99mTc(CO)3-HEHEHE-ZHER3:08699 affibody molecule

Abstract

Imaging of HER3-expressing xenografts in mice using a (99m)Tc(CO) 3-HEHEHE-Z HER3 08699 affibody molecule. Tc(CO) 3 -HEHEHE-Z 08699 was studied over time in mice bearing HER3-expressing xenografts. European Journal of Nuclear Medicine and MolecularResults. HEHEHE-Z 08699 was labeled with 99m Tc(CO) 3 with an isolated yield of >80% and a purity of >99%. Binding of 99m Tc(CO) 3 -HEHEHE-Z 08699 was specific to BT474 and MCF7 (breast cancer), and LS174T (colon cancer) cells. Cellular processing showed rapid binding and relatively quick internalization of receptor/affibody molecule complex (70% cell associated radioactivity was internalized after 24 h). Tumor targeting was receptor mediated and the excretion was predominantly renal. Receptor mediated uptake was also found in liver, lung, stomach, intestine, and salivary glands.At 4 h pi, tumor-to-blood ratios were 7±3 for BT474, and 6±2 for LS174T xenografts. LS174T tumors were visualized by microSPECT 4 h pi. Conclusions. The results of this study suggest feasibility of HER3-imaging in malignant tumors using affibody molecules.

Human Epidermal Growth Factor Receptor 3–Specific Tumor Uptake and Biodistribution of89Zr-MSB0010853 Visualized by Real-Time and Noninvasive PET Imaging

“…Because MSB0010853 is cross-reactive with mouse HER3 and HER3 is expressed on hepatocytes and bile duct cells in the liver, saturation is more likely due to intrahepatic HER3 binding (20). In line with our results, saturation of HER3-dependent liver uptake was also observed in mice injected with 99m Tc-labeled anti-HER3 Affibody molecules, cross-reactive for mouse HER3 ( 99m Tc(CO)3-Z08699-H6 and 99m Tc (CO)3-HEHEHE-ZHER3:08699) (21,22). However, saturation of the liver did not increase blood levels of 99m Tc(CO)3-Z08699-H6 and 99m Tc(CO)3-HEHEHE-ZHER3:08699, 4-6 h after injection.…”

“…Renal uptake of 89 Zr-MSB0010853 is relatively low (,15 %ID/g) as compared with HER3-targeting 99m Tc(CO)3-Z08699-H6 and 99m Tc(CO)3-HEHEHE-ZHER3:08699 (.70 %ID/g) (21,22). However, it is comparable with the renal uptake of 177 Lu-aEGFRaEGFR-aAlb, a similar-sized EGFR binding Nanobody construct with albumin-binding capacity (23).…”

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

“…19,20 The high affinity affibody molecule Z HER3:8698 has been previously selected and radiolabeled with the single photon emission computed tomography (SPECT) radioisotopes 99m Tc and 111 In in order to image HER3 expression in vivo. [21][22][23] To successfully visualize the receptor, the authors had to overcome a variety of challenges including the modest overexpression of the HER3 target (ca 50000 receptors/cell in high-expressing cell lines such as BT-474) and the natural high expression of HER3 in normal organs and tissues (such as intestine, salivary glands and lung). 22,24 Additionally, the same research group reported that the affibody molecule uptake in tumors having modest receptor overexpression is highly influenced by the injected protein dose.…”

“…[21][22][23] To successfully visualize the receptor, the authors had to overcome a variety of challenges including the modest overexpression of the HER3 target (ca 50000 receptors/cell in high-expressing cell lines such as BT-474) and the natural high expression of HER3 in normal organs and tissues (such as intestine, salivary glands and lung). 22,24 Additionally, the same research group reported that the affibody molecule uptake in tumors having modest receptor overexpression is highly influenced by the injected protein dose. They identified 1 µg of radiolabeled protein to be the optimal quantity for HER3 imaging, since higher amounts, associated to lower specific activity, resulted in diminished tumor uptake.…”

“…However, in contrast to the other HER3 targeting affibody based radioligands reported in the literature, high-contrast images were achieved using both radioconjugates already 1 h after injection. 22,23,48 The biodistribution pattern of [ 18 F]AlF-NOTA-Z HER3:8698 produced tumor/blood, tumor/bone and tumor/muscle ratios of 24 (Table 2). These findings suggest that [ 18 F]AlF-NOTA-Z HER3:8698 may be considered the most promising candidate as HER3 imaging agent.…”