Radioligands for Tropomyosin Receptor Kinase (Trk) Positron Emission Tomography Imaging

The tropomyosin receptor kinases family (TrkA, TrkB, and TrkC) supports neuronal growth, survival, and differentiation during development, adult life, and aging. TrkA/B/C downregulation is a prominent hallmark of various neurological disorders including Alzheimer’s disease (AD). Abnormally expressed or overexpressed full-length or oncogenic fusion TrkA/B/C proteins were shown to drive tumorigenesis in a variety of neurogenic and non-neurogenic human cancers and are currently the focus of intensive clinical research. Neurologic and oncologic studies of the spatiotemporal alterations in TrkA/B/C expression and density and the determination of target engagement of emerging antineoplastic clinical inhibitors in normal and diseased tissue are crucially needed but have remained largely unexplored due to the lack of suitable non-invasive probes. Here, we review the recent development of carbon-11- and fluorine-18-labeled positron emission tomography (PET) radioligands based on specifically designed small molecule kinase catalytic domain-binding inhibitors of TrkA/B/C. Basic developments in medicinal chemistry, radiolabeling and translational PET imaging in multiple species including humans are highlighted.

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Positron emission tomography imaging of vascular endothelial growth factor with 64Cu-labeled bevacizumab for non-invasive diagnosis of endometriosis

Journal of Endometriosis and Pelvic Pain Disorders ◽

10.1177/2284026519891576 ◽

2019 ◽

Vol 11 (4) ◽

pp. 194-200

Author(s):

Tumenjargal Amartuvshin ◽

Hirofumi Hanaoka ◽

Aiko Yamaguchi ◽

Yoshito Tsushima

Keyword(s):

Positron Emission Tomography ◽

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Positron Emission Tomography Imaging ◽

Emission Tomography ◽

Vascular Endothelial ◽

Tomography Imaging ◽

Non Invasive ◽

Positron Emission ◽

Endothelial Growth Factor

Introduction: Non-invasive diagnosis of endometriosis remains challenging. A promising approach for diagnosing endometriosis is the molecular imaging of vascular endothelial growth factor because angiogenesis plays a role in the establishment of endometriosis. This study aimed to evaluate the potential of copper-64-labeled bevacizumab, an anti–vascular endothelial growth factor antibody, for endometriosis imaging. Methods: Mouse endometriosis model was prepared by autologous transplantation. The vascular endothelial growth factor expression was evaluated by immunohistochemical staining. Biodistribution study and positron emission tomography imaging were performed at 1, 24, and 48 h after the injection of radiolabeled bevacizumab. Results: The immunohistochemical staining revealed that vascular endothelial growth factor is expressed around the stroma and glandular epithelial cells in the endometriosis lesion. The biodistribution study showed a high uptake of indium-111 bevacizumab in the endometriosis lesion. Positron emission tomography imaging with copper-64-labeled bevacizumab clearly visualized the endometriosis lesions at 24 and 48 h after injection. Conclusion: These results indicate the potential usefulness of copper-64-labeled bevacizumab for endometriosis imaging.

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