In-Cell Determination of Lactate Dehydrogenase Activity in a Luminal Breast Cancer Model – <i>ex vivo</i> Investigation of Excised Xenograft Tumor Slices Using dDNP Hyperpolarized [1-<sup>13</sup>C]pyruvate
Yael Adler-Levy,
Atara Nardi-Schreiber,
Talia Harris,
David Shaul,
Sivaranjan Uppala,
Gal Sapir,
Naama Lev-Cohain,
Jacob Sosna,
Shraga Nahum Goldberg,
J. Moshe Gomori,
Rachel Katz-Brull
Affiliations
Yael Adler-Levy
Department of Radiology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem 9112001, Israel
Atara Nardi-Schreiber
Department of Radiology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem 9112001, Israel
Talia Harris
Department of Radiology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem 9112001, Israel
David Shaul
Department of Radiology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem 9112001, Israel
Sivaranjan Uppala
Department of Radiology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem 9112001, Israel
Gal Sapir
Department of Radiology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem 9112001, Israel
Naama Lev-Cohain
Department of Radiology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem 9112001, Israel
Jacob Sosna
Department of Radiology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem 9112001, Israel
Shraga Nahum Goldberg
Department of Radiology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem 9112001, Israel
J. Moshe Gomori
Department of Radiology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem 9112001, Israel
Rachel Katz-Brull
Department of Radiology, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem 9112001, Israel
[1-13C]pyruvate, the most widely used compound in dissolution-dynamic nuclear polarization (dDNP) magnetic resonance (MR), enables the visualization of lactate dehydrogenase (LDH) activity. This activity had been demonstrated in a wide variety of cancer models, ranging from cultured cells, to xenograft models, to human tumors in situ. Here we quantified the LDH activity in precision cut tumor slices (PCTS) of breast cancer xenografts. The Michigan Cancer Foundation-7 (MCF7) cell-line was chosen as a model for the luminal breast cancer type which is hormone responsive and is highly prevalent. The LDH activity, which was manifested as [1-13C]lactate production in the tumor slices, ranged between 3.8 and 6.1 nmole/nmole adenosine tri-phosphate (ATP) in 1 min (average 4.6 ± 1.0) on three different experimental set-ups consisting of arrested vs. continuous perfusion and non-selective and selective RF pulsation schemes and combinations thereof. This rate was converted to an expected LDH activity in a mass ranging between 3.3 and 5.2 µmole/g in 1 min, using the ATP level of these tumors. This indicated the likely utility of this approach in clinical dDNP of the human breast and may be useful as guidance for treatment response assessment in a large number of tumor types and therapies ex vivo.
