Dataset Information

Noninvasive Evaluation of EGFR Expression of Digestive Tumors Using ^99mTc-MAG₃-Cet-F(ab')₂-Based SPECT/CT Imaging.

ABSTRACT:

Purpose

This study is aimed at investigating the feasibility of cetuximab (Cet) F(ab')₂ fragment- (Cet-F(ab')₂-) based single photon emission tomography/computed tomography (SPECT/CT) for assessing the epidermal growth factor receptor (EGFR) expression in digestive tumor mouse models.

Methods

Cet-F(ab')₂ was synthesized using immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) protease and purified with protein A beads. The product and its in vitro stability in normal saline and 1% bovine serum albumin were analyzed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The EGFR expression in the human colon tumor cell line HT29 and the human stomach tumor cell line MGC803 were verified using western blotting and immunocytochemistry. Cet-F(ab')₂ was conjugated with 5(6)-carboxytetramethylrhodamine succinimidyl ester to demonstrate its binding ability to the MGC803 and HT29 cells. Cet-F(ab')₂ was conjugated with NHS-MAG₃ for ^99mTc radiolabeling. The best imaging time was determined using a biodistribution assay at 1, 4, 16, and 24 h after injection of the ^99mTc-MAG₃-Cet-F(ab')₂ tracer. Furthermore, ^99mTc-MAG₃-Cet-F(ab')₂ SPECT/CT was performed on MGC803 and HT29 tumor-bearing nude mice.

Results

HT29 cells had low EGFR expression while MGC803 cell exhibited the high EGFR expression. Cet-F(ab')₂ and intact cetuximab showed similar high binding ability to MGC803 cells but not to HT29 cells. Cet-F(ab')₂ and ^99mTc-MAG₃-Cet-F(ab')₂ showed excellent in vitro stability. The biodistribution assay showed that the target to nontarget ratio was the highest at 16 h (17.29 ± 5.72, n = 4) after tracer injection. The ^99mTc-MAG₃-Cet-F(ab')₂-based SPECT/CT imaging revealed rapid and sustained tracer uptake in MGC803 tumors rather than in HT29 tumors with high image contrast, which was consistent with the results in vitro.

Conclusion

SPECT/CT imaging using ^99mTc-MAG₃-Cet-F(ab')₂ enables the evaluation of the EGFR expression in murine EGFR-positive tumors, indicating the potential utility for noninvasive evaluation of the EGFR expression in tumors.

SUBMITTER: Shi D

PROVIDER: S-EPMC9281432 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Noninvasive Evaluation of EGFR Expression of Digestive Tumors Using <sup>99m</sup>Tc-MAG<sub>3</sub>-Cet-F(ab')<sub>2</sub>-Based SPECT/CT Imaging.

Shi Dai D Zhang Yiqiu Y Xu Zhan Z Si Zhan Z Cheng Yuan Y Cheng Dengfeng D Liu Guobing G

Molecular imaging 20220624

<h4>Purpose</h4>This study is aimed at investigating the feasibility of cetuximab (Cet) F(ab')<sub>2</sub> fragment- (Cet-F(ab')<sub>2</sub>-) based single photon emission tomography/computed tomography (SPECT/CT) for assessing the epidermal growth factor receptor (EGFR) expression in digestive tumor mouse models.<h4>Methods</h4>Cet-F(ab')<sub>2</sub> was synthesized using immunoglobulin G-degrading enzyme of <i>Streptococcus pyogenes</i> (IdeS) protease and purified with protein A beads. The pr ...[more]

PMID: 35903247

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Project description:PurposeInvestigate the impact of acquisition time and reconstruction parameters on single-photon emission computed tomography/computed tomography (SPECT/CT) image quality with the ultimate aim of finding the shortest possible acquisition time for clinical whole-body SPECT/CT (WB-SPECT/CT) while maintaining image quality METHODS: The National Electrical Manufacturers Association (NEMA) image quality measurements were performed on a SPECT/CT imaging system using a NEMA International Electrotechnical Commission (IEC) phantom with spherical inserts of varying diameter (10-37 mm), filled with 99m Tc in activity sphere-to-background concentration ratio of 8.5:1. A gated acquisition was acquired and binned data were summed to simulate acquisitions of 15, 8, and 3 s per projection angle. Images were reconstructed on a Hermes (HERMES Medical Solutions AB, Stockholm, Sweden) workstation using eight subsets and between 4 and 24 iterations of the three-dimensional (3D) ordered subset expectation maximization (OSEM) algorithm. Reconstructed images were post-smoothed with 3D Gaussian filter ranging from 0 to 12 mm full-width at half maximum (FWHM). Contrast recovery, background variability, and contrast-to-noise ratio were evaluated RESULTS: As expected, the spheres were more clearly defined as acquisition time and count statistics improved. The optimal iteration number and Gaussian filter were determined from the contrast recovery convergence and level of noise. Convergence of contrast recovery was observed at eight iterations while 12 iterations yielded stabilized values at all acquisition times. In addition, it was observed that applying 3D Gaussian filter of 8-12 mm FWHM suppressed the noise and mitigated Gibbs artifacts. Background variability was larger for small spheres than larger spheres and the noise decreased when acquisition time became longer. A contrast-to-noise ratio >5 was reached for the two smallest spheres of 10 and 13 mm at acquisition times of 8 s CONCLUSION: Optimized reconstruction parameters preserved image quality with reduce acquisition time in present study. This study suggests an optimal protocol for clinical 99m Tc SPECT/CT can be reached at 8 s per projection angle, with data reconstructed using 12 iterations and eight subset of the 3D OSEM algorithm and 8 mm Gaussian post-filter.

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Dataset Information

Noninvasive Evaluation of EGFR Expression of Digestive Tumors Using ^99mTc-MAG₃-Cet-F(ab')₂-Based SPECT/CT Imaging.

Purpose

Methods

Results

Conclusion

Publications

Noninvasive Evaluation of EGFR Expression of Digestive Tumors Using <sup>99m</sup>Tc-MAG<sub>3</sub>-Cet-F(ab')<sub>2</sub>-Based SPECT/CT Imaging.

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