25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

Correlation of Serum and Tissue Biomarkers with Hyperpolarized 13C Lactate Production in the Monitoring of Neuroendocrine Prostate Cancer

Not scheduled
4h
Harnack House and Henry Ford Building

Harnack House and Henry Ford Building

Board: 491
Poster Posters

Speaker

Seth Vigneron

Description

Introduction
Neuroendocrine prostate cancer (NEPC) is a subtype that arises as the tumor develops resistance to androgen deprivation therapy (ADT). Preliminary data has displayed the ability of hyperpolarized (HP) 13C pyruvate MRI to detect high-grade PC and provide early evidence of metabolic response to therapy1,2. The goal of this study was to develop a serum marker to measure the development of NEPC during ADT in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model and use immunohistochemical staining (IHC) to quantify the NEPC % of the tumor to correlate with HP 13C MRI findings.

Methods
TRAMP mice that developed 0.5-1cc MRI detectable tumors at ~12 weeks received ADT. Mice with a ≥20% increase in tumor volume two weeks post-treatment were labeled non-responders, containing varying amounts of androgen-insensitive adenocarcinoma (CRPC) and NEPC. Single time-point, frequency-specific 13C 3D imaging was performed 35s after an injection of polarized [1-13C] pyruvate using a gradient spin-echo (GRASE) sequence2. ≈100uL of blood was drawn and an enolase activity assay was performed to determine serum neuron specific enolase (sNSE) activity. Tumor sections were stained for NEPC using NSE and synaptophysin stains and was quantified by pixel HSV values.

Results
sNSE activity increased significantly in ADT resistant mice as compared to mice with androgen-sensitive adenocarcinoma and mice without tumors. sNSE activity was linearly correlated to the amount of NEPC. HP lactate/pyruvate (Lac/Pyr) ratio significantly increased with increasing amounts of neuroendocrine dedifferentiation.

Conclusion
This study demonstrated that sNSE activity correlates to NEPC dedifferentiation as measured by quantitative IHC of the resected tumor, thereby providing a means for selecting tumors for correlation with HP 13C MRI findings and further treatment. Preliminary HP 13C pyruvate studies suggest that the HP Lac/Pyr ratio can differentiate between CRPC and NEPC based on the degree of increased HP 13C lactate production.

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