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Purpose <p>Prostate-specific membrane-antigen positron emission tomography (PSMA PET) is a promising candidate for non-invasive characterization of prostate cancer (PCa). This study evaluated whether PET with tracers [<sup>68</sup>Ga]Ga-PSMA-11 or [<sup>18</sup>F]PSMA-1007 is capable to depict intratumour heterogeneity of histological PSMA expression.</p> Methods <p>Thirty-five patients with biopsy-proven primary PCa without evidence of metastatic disease nor prior interventions were prospectively enrolled. All patients underwent PSMA PET combined with computer tomography (CT) with either [<sup>68</sup>Ga]Ga-PSMA-11 (cohort I, 20 patients) or [<sup>18</sup>F]PSMA-1007 (cohort II, 15 patients) followed by radical prostatectomy. Specimens were scanned by ex-vivo CT and histologically prepared. On digitized whole-mount prostate sections, PCa areas with different morphologies were manually defined and H-Score of immunohistochemical PSMA expression was calculated with assistance by artificial intelligence (AI). PCa areas with similar H-Score were unified in segmentation on ex-vivo CT. After co-registration on PSMA PET-CT, Spearman’s coefficients of PSMA expression to mean and maximum standardized uptake value (SUV<sub>mean</sub> and SUV<sub>max</sub>) were calculated. Furthermore, the agreement of the co-registered tumour areas to gross tumour volume (GTV) in PSMA PET was analysed.</p> Results <p>Thirty-two patients were included in the final analysis. For histological PCa areas, immunohistochemical PSMA expression correlated significantly to SUV<sub>mean</sub> and SUV<sub>max</sub> (<i>p</i> &lt; 0.001, <i>p</i> = 0.001). An approximate linear correlation between H-Score and SUV<sub>mean</sub> / SUV<sub>max</sub> was found for tumour areas larger than 400&#xa0;μm² in histology (<i>p</i> &lt; 0.001). Tumour areas with strong PSMA expression showed a significantly larger overlap to GTV in PSMA PET after co-registration than tumour areas with very low PSMA expression (<i>p</i> &lt; 0.01). No significant differences were found between the two tracer cohorts (<i>p</i> = 0.72).</p> Conclusion <p>PSMA PET with both [<sup>68</sup>Ga]Ga-PSMA-11 or [<sup>18</sup>F]PSMA-1007 is able to detect changes in histological PSMA expression within PCa lesions allowing biologically targeted radiotherapy.</p>

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Can PSMA PET detect intratumour heterogeneity in histological PSMA expression of primary prostate cancer? Analysis of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月17日

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  • Philipp Moritz Adrian Waibel,
  • Ievgen Glavynskyi,
  • Tobias Fechter,
  • Michael Mix,
  • Felix Kind,
  • August Sigle,
  • Cordula Annette Jilg,
  • Christian Gratzke,
  • Martin Werner,
  • Oliver Schilling,
  • Peter Bronsert,
  • Martin Thomas Freitag,
  • Constantinos Zamboglou,
  • Anca-Ligia Grosu,
  • Simon Konrad Benedikt Spohn

摘要

Purpose

Prostate-specific membrane-antigen positron emission tomography (PSMA PET) is a promising candidate for non-invasive characterization of prostate cancer (PCa). This study evaluated whether PET with tracers [68Ga]Ga-PSMA-11 or [18F]PSMA-1007 is capable to depict intratumour heterogeneity of histological PSMA expression.

Methods

Thirty-five patients with biopsy-proven primary PCa without evidence of metastatic disease nor prior interventions were prospectively enrolled. All patients underwent PSMA PET combined with computer tomography (CT) with either [68Ga]Ga-PSMA-11 (cohort I, 20 patients) or [18F]PSMA-1007 (cohort II, 15 patients) followed by radical prostatectomy. Specimens were scanned by ex-vivo CT and histologically prepared. On digitized whole-mount prostate sections, PCa areas with different morphologies were manually defined and H-Score of immunohistochemical PSMA expression was calculated with assistance by artificial intelligence (AI). PCa areas with similar H-Score were unified in segmentation on ex-vivo CT. After co-registration on PSMA PET-CT, Spearman’s coefficients of PSMA expression to mean and maximum standardized uptake value (SUVmean and SUVmax) were calculated. Furthermore, the agreement of the co-registered tumour areas to gross tumour volume (GTV) in PSMA PET was analysed.

Results

Thirty-two patients were included in the final analysis. For histological PCa areas, immunohistochemical PSMA expression correlated significantly to SUVmean and SUVmax (p < 0.001, p = 0.001). An approximate linear correlation between H-Score and SUVmean / SUVmax was found for tumour areas larger than 400 μm² in histology (p < 0.001). Tumour areas with strong PSMA expression showed a significantly larger overlap to GTV in PSMA PET after co-registration than tumour areas with very low PSMA expression (p < 0.01). No significant differences were found between the two tracer cohorts (p = 0.72).

Conclusion

PSMA PET with both [68Ga]Ga-PSMA-11 or [18F]PSMA-1007 is able to detect changes in histological PSMA expression within PCa lesions allowing biologically targeted radiotherapy.