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Intratumoral Distribution of [177Lu]Lu-PSMA-617 Over Time and in Relation to Diagnostic Tracers in Animal Models of Prostate Cancer

  • 0Department of Clinical Sciences Lund, Section for Oncology, Lund University, Lund, Sweden.
Cancer Biotherapy & Radiopharmaceuticals +

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November 28, 2024

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November 28, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Prostate-specific membrane antigen (PSMA) targeted radiopharmaceutical therapy ([177Lu]Lu-PSMA-617) shows heterogeneous intratumoral distribution. PSMA-targeted PET tracers accurately reflect [177Lu]Lu-PSMA-617 distribution in prostate cancer, but tumor regrowth can lead to non-uptake areas.

Area Of Science

  • Nuclear medicine
  • Oncology
  • Radiopharmaceutical science

Background

  • Prostate-specific membrane antigen (PSMA) is a key target for advanced prostate cancer diagnostics and therapeutics.
  • Radiopharmaceutical therapy (RPT) using agents like [177Lu]Lu-PSMA-617 offers a targeted approach.
  • Understanding the intratumoral distribution of RPT agents is crucial for optimizing treatment efficacy.

Purpose Of The Study

  • To investigate the intratumoral distribution of [177Lu]Lu-PSMA-617 over time in prostate cancer xenografts.
  • To compare the distribution of [177Lu]Lu-PSMA-617 with PSMA expression, tumor proliferation (Ki67), and various positron emission tomography (PET) tracers.
  • To assess the correlation between RPT agent distribution and tumor characteristics at different time points.

Main Methods

  • Autoradiography study of [177Lu]Lu-PSMA-617 in LNCaP, 22Rv1, and PC-3 PIP xenografts in mice.
  • Tumor sections were analyzed for radioactivity, PSMA expression, and Ki67 proliferation.
  • Comparison of [177Lu]Lu-PSMA-617 distribution with diagnostic tracers including [68Ga]Ga-PSMA-11, [18F]F-PSMA-1007, [18F]-fluorodeoxyglucose, and [18F]-fluorocholine.

Main Results

  • Heterogeneous intratumoral distribution of [177Lu]Lu-PSMA-617 was observed as early as 20 minutes post-injection.
  • Good overlap between radioactivity, PSMA expression, and proliferation (Ki67) was seen at 1-2 hours, with strongest Ki67 correlation at 48 hours.
  • PSMA-targeted PET tracers showed identical distribution to [177Lu]Lu-PSMA-617, while other tracers had limited overlap. Necrotic tissue uptake was noted only at 2-3 weeks.
  • Tumor regrowth post-therapy resulted in Ki67+/PSMA+ areas with no radioactivity uptake.

Conclusions

  • PSMA-targeted PET tracers can effectively visualize the areas within tumors targeted by [177Lu]Lu-PSMA-617 RPT, at least up to 1 hour post-injection.
  • Tumor regrowth after [177Lu]Lu-PSMA-617 treatment can create radioresistant areas requiring further therapeutic intervention.
  • The findings highlight the importance of assessing intratumoral distribution for optimizing PSMA-targeted RPT strategies in prostate cancer.

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