A robotic system for ‐FMISO PET‐guided intratumoral 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.

Multiparametric Analysis of the Relationship Between Tumor Hypoxia and Perfusion with 18F-Fluoroazomycin Arabinoside and 15O-H2O PET

“…Because 18 F-FAZA is a hypoxia tracer, high uptake of the tracer is expected in low perfused areas, and low uptake is expected in high perfused areas (1,25,26). However, this expectation was not met, raising questions about the reliability of assessing tumor hypoxia with PET.…”

Positron emission tomography to assess hypoxia and perfusion in lung cancer

“…Bentzen et al [195] , Rasey et al [196] , Bentzen et al [197] , Troost et al [198] Bentzen et al [125] , Gagel et al [126] , Bruehlmeier et al [199] , Lawrentschuk et al [200] , O'Donoghue et al [72] , Piert et al [166] , Sørensen et al [201] , Gagel et al [202] , Carlin et al [203] , Chang et al [204] , Mortensen et al [127] Hatano et al [205] , Huang et al [206] , Huang et al [207] , Oehler et al [208] , Cho et al [209] , Troost et al [210] , Matsumoto et al [136] , Troost et al [198] , Dubois et al [211] Dubois et al [211] , Cherk et al [212] , Riesterer et al [213] , Lehmann et al [214] , Chen et al [215] , Campanile et al [216] , Cheng et al [217] , Sato et al [218] , Norikane et al [219] Cherk et al [212] , Eschmann et al [77] , Gagel et al [82] , Koh et al [87] , Rasey et al [220] , Vera et al…”

64Cu-ATSM Reflects pO2 Levels in Human Head and Neck Cancer Xenografts but Not in Colorectal Cancer Xenografts: Comparison with 64CuCl2

“…Moreover, the technique has also been used for evaluation of the spatial distribution of hypoxia PET tracers in a few studies (21,38,39). In this study, uptake of 64 Cu-ATSM and 64 CuCl 2 was measured in human tumor xenograft-bearing nude mice using small-animal PET, and the intratumoral distribution was compared with pO 2 probe measurements.…”