First-in-woman study of in vivo breast cancer metabolism using hyperpolarized [1-13C] pyruvate
Kristin L Granlund1,2, Elizabeth A Morris3, Hebert A Vargas3, Serge K Lyashchenko4, Phillip J DeNoble4, Virgilio A Sacchini5, Ramon A Sosa3, Matthew A Kennedy3, Duane Nicholson3, YanWei W Guo3, Albert P Chen6, James Tropp7, Hedvig Hricak2,3, and Kayvan A Keshari2,3

1Radiology, Memorial Sloan Kettering, New York, NY, United States, 2Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 3Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 4Radiochemistry & Imaging Probes (RMIP) Core, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 5Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 6GE Healthcare, Toronto, ON, Canada, 7GE Healthcare, Fremont, CA, United States

Synopsis

This is a first-in-woman study of hyperpolarized (HP) pyruvate to study in vivo cancer metabolism. A patient with biopsy-proven breast cancer has been scanned with a 2D dynamic hyperpolarized pyruvate protocol. This study aims to evaluate the feasibility and repeatability of HP breast cancer imaging. HP pyruvate imaging may be useful for evaluating treatment response before and after targeted as well as chemo-therapy or radiation treatment.

Purpose

Hyperpolarized (HP) MRI uses an exogenous contrast agent that has been polarized ~10,000x greater than thermal equilibrium polarization. Therefore, there is effectively no background signal, resulting in very high SNR data that can be used to non-invasively measure in vivo metabolism [1]. [1-13C] pyruvate has been used to study the conversion of pyruvate to lactate in human breast cancer cells [2], and the feasibility and safety of HP [1-13C] pyruvate has been demonstrated in prostate cancer patients [3]. In this first in woman study, we demonstrate the feasibility of acquiring dynamic 2D HP 13C spectra in breast cancer patients.

Methods

A 46-year-old woman with biopsy-confirmed invasive ductal carcinoma (NOS) was imaged prior to treatment using a dynamic 2D 13C spectroscopy sequence. The patient was imaged twice to assess repeatability. GMP [1-13C] pyruvic acid (Isotec) was mixed with a stable organic free radical (15 mM, GLP AH11501 sodium salt, GE Healthcare) under sterile conditions and laser welded in a sterile fluid-path (GE Healthcare). Following dissolution, the free radical was filtered out and the resulting solution was tested in a QA module. The patient was injected with 0.43 mL/kg followed by a 20 mL saline flush.

All MR data were acquired on a 3 T wide-bore scanner (GE Healthcare). Anatomic reference images were acquired with the body coil and 13C data were acquired using a clamshell transmit coil (GE Healthcare) and a 4-channel paddle coil (GE Healthcare) positioned anterior to the breast while the patient was prone. A 2D dynamic EPSI sequence was initiated upon completion of the injection, with a 4.3 s temporal resolution. The EPSI waveform was designed to acquire 16 spectra across a 16 cm FOV. Phase encoding was used to acquire 1x1x2 cm3 voxels.

Results

The QC results were 247 mM pyruvate, pH 7.3, 2.7 µM free radical, 36.5°C, 19.0% polarization. The injection began 50 s following dissolution. The acquired spectrum shows pyruvate and lactate signal localized in the lesion (Figure 1). A map of the area under the lactate curve is shown overlaid on a T1-weighted anatomic reference image acquired with the body coil. The high signal in the pyruvate map is agrees well with the location of the tumor on the T1-weighted image.

Discussion

We have demonstrated the feasibility of acquiring hyperpolarized 13C spectra in breast cancer patients. Further study is warranted to optimize timing of the acquisition to account for the delivery of pyruvate to the breast and optimal sampling schemes to efficiently utilize the hyperpolarized signal. Observing the conversion of pyruvate to lactate in breast lesions may be useful for assessing treatment response.

Acknowledgements

NIH R00 EB014328 and S10 OD016422

The Center for Experimental Therapeutic

Mr. William H. and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research

The Pelican Foundation

References

[1] Keshari KR, Wilson DM. Chemistry and biochemistry of 13C hyperpolarized magnetic resonance using dynamic nuclear polarization. Chem Soc Rev 2014; 43(5): 1627-1659.

[2] Harris T, Eliyahu G, Frydman L, Degani H. Kinetics of hyperpolarized 13C-pyruvate transport and metabolism in living human breast cancer cells. http://www.pnas.org/content/106/43/18131.full

[3] Nelson SJ, Kurhanewicz, J, Vigneron DB, et al. Metabolic imaging of patients with prostate cancer using hyperpolarized [1-13C] pyruvate. Sci Trans Med 2013; 5(198): 198ra108.

Figures

T1-weighted image showing an invasive ductal carcinoma (NOS) in a 46-year-old woman. Spectrum showing pyruvate and lactate in a tumor voxel. Pyruvate map overlaid on T1-weighted anatomic reference image showing good correlation with the lesion.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
3690