Background <p>Hepatocellular carcinoma (HCC) shows marked heterogeneity and varying metastatic potential, challenging prognosis and treatment. This study evaluated multitracer PET imaging with [<sup>18</sup>F]FDG, [<sup>18</sup>F]FLT, and [<sup>18</sup>F]ACE to differentiate HCCs by metastatic behavior and explored its prognostic relevance.</p> Methods <p>Four human HCC cell lines with varying metastatic potential (HepG2, QGY7701, MHCC97-H, MHCC97-L) were assessed for in vitro tracer uptake, proliferation, and invasion. Subcutaneous and spontaneous metastasis models were established in nude mice. Tumor uptake of tracers was quantified via microPET/CT. mRNA expression of MMP9 and VEGFR-2 and survival were analyzed. Fisher’s classifier was applied to compare single-, dual-, and triple-tracer datasets with cross-validation.</p> Results <p>Tracer uptake significantly differed among cell lines (<i>p</i> &lt; 0.001). The triple-tracer model ([<sup>18</sup>F]FDG + [ <sup>18</sup>F]FLT + [<sup>18</sup>F]ACE) yielded the lowest classification error rate (0.074) compared with dual tracers (0.085–0.362). In vivo, [<sup>18</sup>F]FDG uptake correlated with metastatic potential, MMP9 and VEGFR-2 expression (r = 0.770–0.830, <i>p</i> &lt; 0.05), and inversely with survival (r = − 0.726, <i>p</i> = 0.005). There is a significant difference in FDG uptake values between high-metastatic and low-metastatic cell lines as well as in tumor model.[<sup>18</sup>F]FLT uptake showed moderate correlation with biomarkers but not with survival, while [<sup>18</sup>F]ACE had no significant discriminative value.</p> Conclusions <p>A multiparameter (multitracer) classification model had superior ability to discriminate four HCC cell lines with different biological behavior compared with dual tracers or single tracer through in vitro cell uptake experiment. [1⁸F]FDG uptake can distinguish between tumor models with high and low metastatic potential, and [1⁸F]FDG uptake can predict the survival time in metastatic models. [<sup>18</sup>F]FDG uptake probably be noninvasive prognostic marker, reflecting tumor heterogeneity and correlating with survival and metastasis-related biomarkers. This approach may aid in clinical stratification and personalized management of HCC.</p>

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Value of Multitracer Imaging in Hepatocellular Carcinomas with Different Metastatic Potential

  • Tingting He,
  • Cong Zhang,
  • Jinming Zhang,
  • Xiaojun Zhang,
  • Ruimin Wang

摘要

Background

Hepatocellular carcinoma (HCC) shows marked heterogeneity and varying metastatic potential, challenging prognosis and treatment. This study evaluated multitracer PET imaging with [18F]FDG, [18F]FLT, and [18F]ACE to differentiate HCCs by metastatic behavior and explored its prognostic relevance.

Methods

Four human HCC cell lines with varying metastatic potential (HepG2, QGY7701, MHCC97-H, MHCC97-L) were assessed for in vitro tracer uptake, proliferation, and invasion. Subcutaneous and spontaneous metastasis models were established in nude mice. Tumor uptake of tracers was quantified via microPET/CT. mRNA expression of MMP9 and VEGFR-2 and survival were analyzed. Fisher’s classifier was applied to compare single-, dual-, and triple-tracer datasets with cross-validation.

Results

Tracer uptake significantly differed among cell lines (p < 0.001). The triple-tracer model ([18F]FDG + [ 18F]FLT + [18F]ACE) yielded the lowest classification error rate (0.074) compared with dual tracers (0.085–0.362). In vivo, [18F]FDG uptake correlated with metastatic potential, MMP9 and VEGFR-2 expression (r = 0.770–0.830, p < 0.05), and inversely with survival (r = − 0.726, p = 0.005). There is a significant difference in FDG uptake values between high-metastatic and low-metastatic cell lines as well as in tumor model.[18F]FLT uptake showed moderate correlation with biomarkers but not with survival, while [18F]ACE had no significant discriminative value.

Conclusions

A multiparameter (multitracer) classification model had superior ability to discriminate four HCC cell lines with different biological behavior compared with dual tracers or single tracer through in vitro cell uptake experiment. [1⁸F]FDG uptake can distinguish between tumor models with high and low metastatic potential, and [1⁸F]FDG uptake can predict the survival time in metastatic models. [18F]FDG uptake probably be noninvasive prognostic marker, reflecting tumor heterogeneity and correlating with survival and metastasis-related biomarkers. This approach may aid in clinical stratification and personalized management of HCC.