Figures & data
Figure 1. (A) Structural formula of the electron paramagnetic agent OX063, a trityl radical. (B) Overhauser MRI pulse-sequence diagram showing B0 filed cycling and RF and field-gradient waveforms. (C) Interleaved (“EPR off” and “EPR on”) OMRI images (coronal) of a female C3H mouse, bearing SCC tumor on the right hind leg, demonstrating the Overhauser enhancement. Both images were acquired in the presence of the contrast agent. (D) pO2 images of a mouse with SCC tumor during air breathing (upper) and carbogen breathing (lower). The expanded tumor region is given at the right (see [Citation18]).
![Figure 1. (A) Structural formula of the electron paramagnetic agent OX063, a trityl radical. (B) Overhauser MRI pulse-sequence diagram showing B0 filed cycling and RF and field-gradient waveforms. (C) Interleaved (“EPR off” and “EPR on”) OMRI images (coronal) of a female C3H mouse, bearing SCC tumor on the right hind leg, demonstrating the Overhauser enhancement. Both images were acquired in the presence of the contrast agent. (D) pO2 images of a mouse with SCC tumor during air breathing (upper) and carbogen breathing (lower). The expanded tumor region is given at the right (see [Citation18]).](/cms/asset/6319bc02-cbc4-4f5c-b047-6d0706887217/ionc_a_819118_f0001_b.jpg)
Figure 2. (A) In vivo EPR oxygen mapping of SCC tumor-bearing mouse leg, and visualization of the effect of carbogen (95% O2 plus 5% CO2) breathing on tumor pO2. (B) Histograms of pO2 in the tumor region of the same mouse breathing medical air (blue) and carbogen (red). A net increase in the median pO2 was noted upon carbogen breathing. (see [Citation24]). (C) Non-invasive imaging of chronic and cycling tumor hypoxia in a mouse implanted with a SCCVII tumor. 3D-EPR oxygen images were obtained every 3 min during a 30 min time window. Three representative images acquired at 3, 18, and 27 min are shown. Two ROIs were selected in the tumor (1 and 2), and pO2 was assessed in the ROIs over 30 min. (D) ROI 1 (open circles) indicates a chronically hypoxic region; ROI 2 (closed circles) represents a cycling hypoxic region showing temporal fluctuations in pO2. C, Time-averaged pO2 map (left) and standard deviation map of pO2 (right) calculated from the 10 images taken in the 30 min time window (see [Citation19]).
![Figure 2. (A) In vivo EPR oxygen mapping of SCC tumor-bearing mouse leg, and visualization of the effect of carbogen (95% O2 plus 5% CO2) breathing on tumor pO2. (B) Histograms of pO2 in the tumor region of the same mouse breathing medical air (blue) and carbogen (red). A net increase in the median pO2 was noted upon carbogen breathing. (see [Citation24]). (C) Non-invasive imaging of chronic and cycling tumor hypoxia in a mouse implanted with a SCCVII tumor. 3D-EPR oxygen images were obtained every 3 min during a 30 min time window. Three representative images acquired at 3, 18, and 27 min are shown. Two ROIs were selected in the tumor (1 and 2), and pO2 was assessed in the ROIs over 30 min. (D) ROI 1 (open circles) indicates a chronically hypoxic region; ROI 2 (closed circles) represents a cycling hypoxic region showing temporal fluctuations in pO2. C, Time-averaged pO2 map (left) and standard deviation map of pO2 (right) calculated from the 10 images taken in the 30 min time window (see [Citation19]).](/cms/asset/001598c3-041c-4fcf-8ceb-4381da9e3979/ionc_a_819118_f0002_b.jpg)
Figure 3. Hyperpolarized 13C metabolic images of a TRAMP mouse. Upper: Hyperpolarized 13C lactate image following the injection of hyperpolarized [1-13C]pyruvate, overlaid on T2-weighted 1H image. Middle: Hyperpolarized 13C spectra of primary and metastatic tumor regions. Lower: Representative H&E-stained sections and hyperpolarized 13C spectra for one case from each of the histologically defined groups. The 3D MRSI shows substantially elevated lactate in the high-grade primary tumor compared with the low-grade tumor. Ala, alanine; Lac, lactate; Pyr, pyruvate (see [Citation22]).
![Figure 3. Hyperpolarized 13C metabolic images of a TRAMP mouse. Upper: Hyperpolarized 13C lactate image following the injection of hyperpolarized [1-13C]pyruvate, overlaid on T2-weighted 1H image. Middle: Hyperpolarized 13C spectra of primary and metastatic tumor regions. Lower: Representative H&E-stained sections and hyperpolarized 13C spectra for one case from each of the histologically defined groups. The 3D MRSI shows substantially elevated lactate in the high-grade primary tumor compared with the low-grade tumor. Ala, alanine; Lac, lactate; Pyr, pyruvate (see [Citation22]).](/cms/asset/0c6bfe13-2927-44e4-ab69-d087a871ad5c/ionc_a_819118_f0003_b.jpg)
Figure 4. Monocarboxylate transporter 1 (MCT1) dependent uptake of [1-13C]pyruvate. (A) Comparison of tumor pO2 and MCT1 expression in vivo. After EPR oxygen imaging and following anatomic MRI scans, tumor tissue slice corresponding to the particular slice of pO2 map was exsected and immunostaining of HIF-1a (blue) and MCT1 (red) was conducted(B) Pretreatment with CHC significantly suppressed lactate/total 13C and lactate/pyruvate ratios calculated from whole tumor regions in 13C MRI images. (C) Metabolic 13C MRI of hyperpolarized 13C-labeled pyruvate in SCC tumors with or without pretreatment of MCT1 inhibitor CHC obtained 30 s after [1-13C]pyruvate injection (see [Citation25]).
![Figure 4. Monocarboxylate transporter 1 (MCT1) dependent uptake of [1-13C]pyruvate. (A) Comparison of tumor pO2 and MCT1 expression in vivo. After EPR oxygen imaging and following anatomic MRI scans, tumor tissue slice corresponding to the particular slice of pO2 map was exsected and immunostaining of HIF-1a (blue) and MCT1 (red) was conducted(B) Pretreatment with CHC significantly suppressed lactate/total 13C and lactate/pyruvate ratios calculated from whole tumor regions in 13C MRI images. (C) Metabolic 13C MRI of hyperpolarized 13C-labeled pyruvate in SCC tumors with or without pretreatment of MCT1 inhibitor CHC obtained 30 s after [1-13C]pyruvate injection (see [Citation25]).](/cms/asset/410daf16-69b7-4167-bb93-01182690b1dd/ionc_a_819118_f0004_b.jpg)