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Purpose <p>Monocarboxylate transporters (MCTs) play a pivotal role in tumor metabolic symbiosis, acid resistance, and metastatic progression. Herein, we report the development of [<sup>18</sup>F]FEtO-CHC, a novel MCTs-targeted positron emission tomography (PET) radiotracer, and systematically evaluate its potential for non-invasive tumor imaging.</p> Procedures <p>The radiosynthesis of [<sup>18</sup>F]FEtO-CHC and its non-radioactive analog was achieved through optimized precursor synthesis and fluorination protocols. Comprehensive <i>in vitro</i> characterization encompassed: radiochemical purity and stability assessments, cellular uptake kinetics and inhibition assays in MCT-expressing BxPC3 (pancreatic) and 4T1 (breast) cancer models, biodistribution and dynamic micro-PET/CT imaging in tumor-bearing murine models.</p> Results <p>[<sup>18</sup>F]FEtO-CHC, a CHC-derived radioligand, was synthesized via streamlined one-step radiosynthesis with 52.08 ± 6.74% decay-corrected yield (<i>n</i>=7), &gt;99% radiochemical purity, and excellent stability. Cellular studies demonstrated MCTs-dependent uptake with significant suppression (&gt;70%) by α-CHC competition. <i>In vivo</i> pharmacokinetics revealed favorable metabolic stability with dual hepatorenal clearance. Tumor uptake correlated with MCT expression levels, as confirmed by immunohistochemistry.</p> Conclusions <p>This study establishes an efficient one-step radiosynthetic approach for [<sup>18</sup>F]FEtO-CHC production and validates its specificity as a MCT-targeted PET probe, offering potential utility in tumor imaging with further structural optimization.</p>

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One-step Radiosynthesis and Preclinical Evaluation of Molecular Tracer [18F]FEtO-CHC Targeting Monocarboxylate Transporters for PET Imaging in Tumor-bearing Mice

  • 期刊论文

  • 发表日期：

    2025年6月11日

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  • Dongmei Shi,
  • Ling Liu,
  • Di Zhang,
  • Yuzhou Zheng,
  • Wenhao Hu,
  • Ping Wu,
  • Xinzhong Hao,
  • Haiyan Liu,
  • Jie Gao,
  • Jianguo Li,
  • Zhifang Wu,
  • Sijin Li,
  • Hongliang Wang

摘要

Purpose

Monocarboxylate transporters (MCTs) play a pivotal role in tumor metabolic symbiosis, acid resistance, and metastatic progression. Herein, we report the development of [18F]FEtO-CHC, a novel MCTs-targeted positron emission tomography (PET) radiotracer, and systematically evaluate its potential for non-invasive tumor imaging.

Procedures

The radiosynthesis of [18F]FEtO-CHC and its non-radioactive analog was achieved through optimized precursor synthesis and fluorination protocols. Comprehensive in vitro characterization encompassed: radiochemical purity and stability assessments, cellular uptake kinetics and inhibition assays in MCT-expressing BxPC3 (pancreatic) and 4T1 (breast) cancer models, biodistribution and dynamic micro-PET/CT imaging in tumor-bearing murine models.

Results

[18F]FEtO-CHC, a CHC-derived radioligand, was synthesized via streamlined one-step radiosynthesis with 52.08 ± 6.74% decay-corrected yield (n=7), >99% radiochemical purity, and excellent stability. Cellular studies demonstrated MCTs-dependent uptake with significant suppression (>70%) by α-CHC competition. In vivo pharmacokinetics revealed favorable metabolic stability with dual hepatorenal clearance. Tumor uptake correlated with MCT expression levels, as confirmed by immunohistochemistry.

Conclusions

This study establishes an efficient one-step radiosynthetic approach for [18F]FEtO-CHC production and validates its specificity as a MCT-targeted PET probe, offering potential utility in tumor imaging with further structural optimization.