Targeting Amyloids with [18F]AV-45 for Medullary Thyroid Carcinoma Positron Emission Tomography/Computed Tomography Imaging: A Pilot Clinical Study

Chun Li; Pengxin  Zhang; Ruirui  Nie; Xiaoyan Gong; Jinghui Xie; Zilin Yu; Chengdong  Wang; Hua  Zhang; Ran Yan; Zhi Lu

doi:10.1021/acs.molpharmaceut.1c00680

Targeting Amyloids with [¹⁸F]AV-45 for Medullary Thyroid Carcinoma Positron Emission Tomography/Computed Tomography Imaging: A Pilot Clinical Study

Chun Li, Pengxin Zhang, Ruirui Nie, Xiaoyan Gong, Jinghui Xie, Zilin Yu, Chengdong Wang, Hua Zhang, Ran Yan, Zhi Lu

Imaging Chemistry & Biology

Research output: Contribution to journal › Article › peer-review

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Abstract

Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor with a high recurrence rate. Amyloid plaques formed from the misfolding of calcitonin are the key characteristics of MTC. Herein, we conducted a first-in-human pilot clinical study by applying a β-amyloid-specific radiotracer, [ F]AV-45, to positron emission tomography (PET)/computed tomography (CT) imaging of MTC. The presence of amyloid plaques in the tumor tissue sections from five MTC patients was confirmed by hematoxylin and eosin (H&E) and Congo Red staining. [ F]AV-45 selectively accumulated in the amyloid plaques in the continued tumor tissue sections with similar distribution patterns to the H&E and Congo Red staining. In addition, the [ F]AV-45 uptake can be largely blocked by its nonradioactive reference compound. The [ F]AV-45 accumulation in the thyroid, neck lymph nodes, and muscles in healthy human subjects is close to the background indicated by PET/CT imaging. In the comparison PET/CT imaging study of a recurrent MTC patient, 2-deoxy-2-[ F]fluoro-d-glucose ([ F]FDG) showed an elevated uptake by multiple neck lymph nodes. In contrast, only one of these neck lymph nodes had increased [ F]AV-45 uptake. Postoperative histopathological analysis confirmed the [ F]AV-45 PET-positive lymph node as MTC with amyloid deposition, while other [ F]FDG positive lymph nodes were free from MTC and amyloid plaques. Thus, [ F]AV-45 showed the promise for the clinical PET/CT imaging of MTC.

Original language	English
Pages (from-to)	584-591
Number of pages	8
Journal	Molecular Pharmaceutics
Volume	19
Issue number	2
Early online date	4 Jan 2022
DOIs	https://doi.org/10.1021/acs.molpharmaceut.1c00680
Publication status	Published - 7 Feb 2022

Keywords

Drug Discovery
Pharmaceutical Science
Molecular Medicine

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10.1021/acs.molpharmaceut.1c00680

Targeting the Amyloid_LI_Publishedonline4January2022_GREEN AAMAccepted author manuscript, 867 KB

Cite this

@article{5d32add1fde2412bafcb06d96536aba8,

title = "Targeting Amyloids with [18F]AV-45 for Medullary Thyroid Carcinoma Positron Emission Tomography/Computed Tomography Imaging: A Pilot Clinical Study",

abstract = "Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor with a high recurrence rate. Amyloid plaques formed from the misfolding of calcitonin are the key characteristics of MTC. Herein, we conducted a first-in-human pilot clinical study by applying a β-amyloid-specific radiotracer, [ F]AV-45, to positron emission tomography (PET)/computed tomography (CT) imaging of MTC. The presence of amyloid plaques in the tumor tissue sections from five MTC patients was confirmed by hematoxylin and eosin (H&E) and Congo Red staining. [ F]AV-45 selectively accumulated in the amyloid plaques in the continued tumor tissue sections with similar distribution patterns to the H&E and Congo Red staining. In addition, the [ F]AV-45 uptake can be largely blocked by its nonradioactive reference compound. The [ F]AV-45 accumulation in the thyroid, neck lymph nodes, and muscles in healthy human subjects is close to the background indicated by PET/CT imaging. In the comparison PET/CT imaging study of a recurrent MTC patient, 2-deoxy-2-[ F]fluoro-d-glucose ([ F]FDG) showed an elevated uptake by multiple neck lymph nodes. In contrast, only one of these neck lymph nodes had increased [ F]AV-45 uptake. Postoperative histopathological analysis confirmed the [ F]AV-45 PET-positive lymph node as MTC with amyloid deposition, while other [ F]FDG positive lymph nodes were free from MTC and amyloid plaques. Thus, [ F]AV-45 showed the promise for the clinical PET/CT imaging of MTC.",

keywords = "Drug Discovery, Pharmaceutical Science, Molecular Medicine",

author = "Chun Li and Pengxin Zhang and Ruirui Nie and Xiaoyan Gong and Jinghui Xie and Zilin Yu and Chengdong Wang and Hua Zhang and Ran Yan and Zhi Lu",

note = "Funding Information: Z.L. thanks the support from the Natural Science Foundation of Liaoning Province of China (Grant no. 20180530048). R.Y. thanks the Royal Society for the International Exchanges Grant (IEC/NSFC/170006). The research was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London, the Wellcome/EPSRC Centre for Medical Engineering at King{\textquoteright}s College London [WT 203148/Z/16/Z], the King{\textquoteright}s College London and UCL Comprehensive Cancer Imaging Centre funded by CRUK and EPSRC in association with the MRC and DoH (England), the Experimental Cancer Medicine Centre at King{\textquoteright}s College, and the King{\textquoteright}s Health Partners/King{\textquoteright}s College London Cancer Research UK Cancer Centre. This work was also supported by the EPSRC Programme Grant [EP/S032789/1]. Funding Information: The Natural Science Foundation of Liaoning Province of China (Grant no. 20180530048); the Royal Society for the International Exchanges Grant (IEC/NSFC/170,006); the Wellcome/EPSRC Centre for Medical Engineering at King{\textquoteright}s College London [WT 203148/Z/16/Z]; and the EPSRC Programme Grant [EP/S032789/1]. Publisher Copyright: {\textcopyright} 2021 The Authors. Published by American Chemical Society.",

year = "2022",

month = feb,

day = "7",

doi = "10.1021/acs.molpharmaceut.1c00680",

language = "English",

volume = "19",

pages = "584--591",

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T1 - Targeting Amyloids with [18F]AV-45 for Medullary Thyroid Carcinoma Positron Emission Tomography/Computed Tomography Imaging: A Pilot Clinical Study

AU - Li, Chun

AU - Zhang, Pengxin

AU - Nie, Ruirui

AU - Gong, Xiaoyan

AU - Xie, Jinghui

AU - Yu, Zilin

AU - Wang, Chengdong

AU - Zhang, Hua

AU - Yan, Ran

AU - Lu, Zhi

N1 - Funding Information: Z.L. thanks the support from the Natural Science Foundation of Liaoning Province of China (Grant no. 20180530048). R.Y. thanks the Royal Society for the International Exchanges Grant (IEC/NSFC/170006). The research was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, the Wellcome/EPSRC Centre for Medical Engineering at King’s College London [WT 203148/Z/16/Z], the King’s College London and UCL Comprehensive Cancer Imaging Centre funded by CRUK and EPSRC in association with the MRC and DoH (England), the Experimental Cancer Medicine Centre at King’s College, and the King’s Health Partners/King’s College London Cancer Research UK Cancer Centre. This work was also supported by the EPSRC Programme Grant [EP/S032789/1]. Funding Information: The Natural Science Foundation of Liaoning Province of China (Grant no. 20180530048); the Royal Society for the International Exchanges Grant (IEC/NSFC/170,006); the Wellcome/EPSRC Centre for Medical Engineering at King’s College London [WT 203148/Z/16/Z]; and the EPSRC Programme Grant [EP/S032789/1]. Publisher Copyright: © 2021 The Authors. Published by American Chemical Society.

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Y1 - 2022/2/7

N2 - Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor with a high recurrence rate. Amyloid plaques formed from the misfolding of calcitonin are the key characteristics of MTC. Herein, we conducted a first-in-human pilot clinical study by applying a β-amyloid-specific radiotracer, [ F]AV-45, to positron emission tomography (PET)/computed tomography (CT) imaging of MTC. The presence of amyloid plaques in the tumor tissue sections from five MTC patients was confirmed by hematoxylin and eosin (H&E) and Congo Red staining. [ F]AV-45 selectively accumulated in the amyloid plaques in the continued tumor tissue sections with similar distribution patterns to the H&E and Congo Red staining. In addition, the [ F]AV-45 uptake can be largely blocked by its nonradioactive reference compound. The [ F]AV-45 accumulation in the thyroid, neck lymph nodes, and muscles in healthy human subjects is close to the background indicated by PET/CT imaging. In the comparison PET/CT imaging study of a recurrent MTC patient, 2-deoxy-2-[ F]fluoro-d-glucose ([ F]FDG) showed an elevated uptake by multiple neck lymph nodes. In contrast, only one of these neck lymph nodes had increased [ F]AV-45 uptake. Postoperative histopathological analysis confirmed the [ F]AV-45 PET-positive lymph node as MTC with amyloid deposition, while other [ F]FDG positive lymph nodes were free from MTC and amyloid plaques. Thus, [ F]AV-45 showed the promise for the clinical PET/CT imaging of MTC.

AB - Medullary thyroid carcinoma (MTC) is a malignant neuroendocrine tumor with a high recurrence rate. Amyloid plaques formed from the misfolding of calcitonin are the key characteristics of MTC. Herein, we conducted a first-in-human pilot clinical study by applying a β-amyloid-specific radiotracer, [ F]AV-45, to positron emission tomography (PET)/computed tomography (CT) imaging of MTC. The presence of amyloid plaques in the tumor tissue sections from five MTC patients was confirmed by hematoxylin and eosin (H&E) and Congo Red staining. [ F]AV-45 selectively accumulated in the amyloid plaques in the continued tumor tissue sections with similar distribution patterns to the H&E and Congo Red staining. In addition, the [ F]AV-45 uptake can be largely blocked by its nonradioactive reference compound. The [ F]AV-45 accumulation in the thyroid, neck lymph nodes, and muscles in healthy human subjects is close to the background indicated by PET/CT imaging. In the comparison PET/CT imaging study of a recurrent MTC patient, 2-deoxy-2-[ F]fluoro-d-glucose ([ F]FDG) showed an elevated uptake by multiple neck lymph nodes. In contrast, only one of these neck lymph nodes had increased [ F]AV-45 uptake. Postoperative histopathological analysis confirmed the [ F]AV-45 PET-positive lymph node as MTC with amyloid deposition, while other [ F]FDG positive lymph nodes were free from MTC and amyloid plaques. Thus, [ F]AV-45 showed the promise for the clinical PET/CT imaging of MTC.

KW - Drug Discovery

KW - Pharmaceutical Science

KW - Molecular Medicine

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U2 - 10.1021/acs.molpharmaceut.1c00680

DO - 10.1021/acs.molpharmaceut.1c00680

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