Preclinical Evaluation of 99mTc-MAG3-5-Fab Targeting TREM2 in Lung Cancer Mouse Models: A Comparison with 99mTc-MAG3-5-F(ab′)2

Shi, Dai; Fu, Wenhui; Tan, Hui; Lin, Qingyu; Shi, Hongcheng; Cheng, Dengfeng

doi:10.1021/acs.molpharmaceut.3c00870

Mol. Pharmaceutics

2023

DOI: 10.1021/acs.molpharmaceut.3c00870

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Preclinical Evaluation of ^99mTc-MAG₃-5-Fab Targeting TREM2 in Lung Cancer Mouse Models: A Comparison with ^99mTc-MAG₃-5-F(ab′)₂

Dai Shi,

Wenhui Fu,

Hui Tan

et al.

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2024

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Cited by 1 publication

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Transplanted Murine Tumours SPECT Imaging with 99mTc Delivered with an Artificial Recombinant Protein

Pozdniakova,

Lipengolts,

Skribitsky

et al. 2024

IJMS

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99mTc is a well-known radionuclide that is widely used and readily available for SPECT/CT (Single-Photon Emission Computed Tomography) diagnosis. However, commercial isotope carriers are not specific enough to tumours, rapidly clear from the bloodstream, and are not safe. To overcome these limitations, we suggest immunologically compatible recombinant proteins containing a combination of metal binding sites as 99mTc chelators and several different tumour-specific ligands for early detection of tumours. E1b protein containing metal-binding centres and tumour-specific ligands targeting integrin αvβ3 and nucleolin, as well as a short Cys-rich sequence, was artificially constructed. It was produced in E. coli, purified by metal-chelate chromatography, and used to obtain a complex with 99mTc. This was administered intravenously to healthy Balb/C mice at an activity dose of about 80 MBq per mouse, and the biodistribution was studied by SPECT/CT for 24 h. Free sodium 99mTc-pertechnetate at the same dose was used as a reference. The selectivity of 99mTc-E1b and the kinetics of isotope retention in tumours were then investigated in experiments in C57Bl/6 and Balb/C mice with subcutaneously transplanted lung carcinoma (LLC) or mammary adenocarcinoma (Ca755, EMT6, or 4T1). The radionuclide distribution ratio in tumour and adjacent normal tissue (T/N) steadily increased over 24 h, reaching 15.7 ± 4.2 for EMT6, 16.5 ± 3.8 for Ca755, 6.7 ± 4.2 for LLC, and 7.5 ± 3.1 for 4T1.

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Transplanted Murine Tumours SPECT Imaging with 99mTc Delivered with an Artificial Recombinant Protein

Pozdniakova,

Lipengolts,

Skribitsky

et al. 2024

IJMS

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show abstract

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Preclinical Evaluation of ^99mTc-MAG₃-5-Fab Targeting TREM2 in Lung Cancer Mouse Models: A Comparison with ^99mTc-MAG₃-5-F(ab′)₂

Cited by 1 publication

References 26 publications

Transplanted Murine Tumours SPECT Imaging with 99mTc Delivered with an Artificial Recombinant Protein

Transplanted Murine Tumours SPECT Imaging with 99mTc Delivered with an Artificial Recombinant Protein

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