Abstract 1501A: Detecting lung metastases by hyperpolarized NMR technique: A pilot study
Authors: Xu He N. , Pourfathi Mehrdad , Shaghaghi Hoora , Kadlececk Stephen , Profka Harrilla , Rizi Rahim , Li Lin Z. 
Published: August 2015

Abstract
Purpose: Early detection of lung-residing tumor is of high importance as 1) lung cancer is the number one leading cause of cancer death in the US and early-stage lung cancer was found to be associated with lower mortality than late-stage disease; 2) the lung is one of most common sites of metastasis for various cancers, and metastasis accounts for ∼90% of cancer death. Early confirmation of lung metastasis is expected to significantly change the therapeutic strategies. Currently, the major tools for screening lung-residing tumors in high risk populations include radiography and low dose CT. However, their false positive and over-diagnosis rates are very high (&gt;90%). We aimed to explore the feasibility of employing hyperpolarized-13C NMR (HP-13C-NMR) technique for the early detection of primary lung cancer and lung metastases. HP-13C-NMR is a non-invasive spectroscopy/imaging technique that enhances regular NMR signal by ∼10000 times and has already been demonstrated in both preclinical and clinical cancer studies to quantify cancer enzymatic activities in vivo. Since cancer cells produce more lactate via the Warburg effect, by measuring the kinetics of lactate dehydrogenase, we expect to see the difference between the normal and cancerous lungs.
Methods: We used the perfused mouse lungs infested with metastatic breast cancer cells to prove the concept. Nude mice of 7-9 weeks old were injected red fluorescent protein-transfected MDA-MB-231 cell line via tail vein. Tumors were allowed to grow for 4-39 weeks. Lung metastasis was confirmed by optical imaging in vivo. Perfused mouse lungs were placed in a NMR tube (9.4T vertical bore magnet). The lung viability was monitored using 31P spectroscopy before and after HP-13C-pyruvate injection. 8mM [1- 13C] pyruvate polarized via dynamic nuclear polarization (Hypersense, Oxford Instruments) was infused for HP-13C NMR. A series of 13C NMR spectra was acquired (α = 15°) every second for 5 min followed by data processing using custom MATLAB routines to obtain the time courses of pyruvate (Pyr) and lactate (Lac) signals and their ratio, Lac/Pyr.
Results: Comparison between the normal lungs (N = 6) and the cancerous lungs (N = 8) shows 70% increase in maximum lactate (p = 0.041) and 94% increase in Lac/Pyr (p = 0.059) due to cancer formation. The standard deviations of the maximum lactate and the ratio in cancerous lung group are much larger than the control group, suggesting a large inter-lung heterogeneity in the cancerous lungs, presumably caused by different amount of metastases. Our next step is to evaluate the amount of metastases in these lungs by H&E staining and quantitatively investigate the correlation between the hyperpolarized measurements and the amount of metastases.
Conclusions: Our preliminary results warrant further investigation for the potential of developing a novel HP-NMR technique for the early detection of lung cancer/metastasis in vivo.
Citation Format: He N. Xu, Mehrdad Pourfathi, Hoora Shaghaghi, Stephen Kadlececk, Harrilla Profka, Rahim Rizi, Lin Z. Li. Detecting lung metastases by hyperpolarized NMR technique: A pilot study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1501A. doi:10.1158/1538-7445.AM2015-1501A