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.