A robotic system for 18F-FMISO PET-guided intratumoral pO2 measurements

Abstract

An image-guided robotic system was used to measure the oxygen tension (pO2) in rodent tumor xenografts using interstitial probes guided by tumor hypoxia PET images. Rats with approximately 1 cm diameter tumors were anesthetized and immobilized in a custom-fabricated whole-body mold. Imaging was performed using a dedicated small-animal PET scanner (R4 or Focus 120 microPET) approximately 2 h after the injection of the hypoxia tracer 18F-fluoromisonidazole (18F-FMISO). The coordinate systems of the robot and PET were registered based on fiducial markers in the rodent bed visible on the PET images. Guided by the 3D microPET image set, measurements were performed at various locations in the tumor and compared to the corresponding 18F-FMISO image intensity at the respective measurement points. Experiments were performed on four tumor-bearing rats with 4 (86), 3 (80), 7 (162), and 8 (235) measurement tracks (points) for each experiment. The 18F-FMISO image intensities were inversely correlated with the measured pO2, with a Pearson coefficient ranging from -0.14 to -0.97 for the 22 measurement tracks. The cumulative scatterplots of pO2 versus image intensity yielded a hyperbolic relationship, with correlation coefficients of 0.52, 0.48, 0.64, and 0.73, respectively, for the four tumors. In conclusion, PET image-guided pO2 measurement is feasible with this robot system and, more generally, this system will permit point-by-point comparison of physiological probe measurements and image voxel values as a means of validating molecularly targeted radiotracers. Although the overall data fitting suggested that 18F-FMISO may be an effective hypoxia marker, the use of static 18F-FMISO PET postinjection scans to guide radiotherapy might be problematic due to the observed high variation in some individual data pairs from the fitted curve, indicating potential temporal fluctuation of oxygen tension in individual voxels or possible suboptimal imaging time postadministration of hypoxia-related trapping of 18F-FMISO.

Figure 1

(a) The image-guided robot system. (b) Image-guided measurement of oxygen level using the Oxylite probe.

Figure 2

Image intensity values and pO₂ measurements as a function of measurement point for the (a) first, (b) second, (c) third and (d) fourth tracks of the first experiment. Measurements were done every 0.5 mm. R is the Pearson product-moment correlation coefficient.

Figure 3

Scatterplot of pO₂ versus image intensity for all tracks of (a) first, (b) second, (c) third, and (d) fourth experiments. Gray curve is the best fit of the data to a hyperbolic function. R: The correlation coefficient for the fit.

Figure 4

Microscopic imaging study results for the slice containing measurement points 5–9 of Fig. 2a. (a) HE stain. (b) Overlay of pimonidazole, Hoechst 33342, and HE stains. Circles are the location of the fiber-optic probe.

Figure 5

Microscopic imaging study results for the slice containing measurement points 16–20 of Fig. 2a. (a) HE stain. (b) Overlay of pimonidazole, Hoechst 33342, and HE stains. Circles are the location of the fiber-optic probe.