Impact of PET and MRI threshold-based tumor volume segmentation on patient-specific targeted radionuclide therapy dosimetry using CLR1404

Abstract

Variations in tumor volume segmentation methods in targeted radionuclide therapy (TRT) may lead to dosimetric uncertainties. This work investigates the impact of PET and MRI threshold-based tumor segmentation on TRT dosimetry in patients with primary and metastatic brain tumors. In this study, PET/CT images of five brain cancer patients were acquired at 6, 24, and 48 h post-injection of ¹²⁴I-CLR1404. The tumor volume was segmented using two standardized uptake value (SUV) threshold levels, two tumor-to-background ratio (TBR) threshold levels, and a T1 Gadolinium-enhanced MRI threshold. The dice similarity coefficient (DSC), jaccard similarity coefficient (JSC), and overlap volume (OV) metrics were calculated to compare differences in the MRI and PET contours. The therapeutic ¹³¹I-CLR1404 voxel-level dose distribution was calculated from the ¹²⁴I-CLR1404 activity distribution using RAPID, a Geant4 Monte Carlo internal dosimetry platform. The TBR, SUV, and MRI tumor volumes ranged from 2.3-63.9 cc, 0.1-34.7 cc, and 0.4-11.8 cc, respectively. The average ± standard deviation (range) was 0.19 ± 0.13 (0.01-0.51), 0.30 ± 0.17 (0.03-0.67), and 0.75 ± 0.29 (0.05-1.00) for the JSC, DSC, and OV, respectively. The DSC and JSC values were small and the OV values were large for both the MRI-SUV and MRI-TBR combinations because the regions of PET uptake were generally larger than the MRI enhancement. Notable differences in the tumor dose volume histograms were observed for each patient. The mean (standard deviation) ¹³¹I-CLR1404 tumor doses ranged from 0.28-1.75 Gy GBq^-1 (0.07-0.37 Gy GBq^-1). The ratio of maximum-to-minimum mean doses for each patient ranged from 1.4-2.0. The tumor volume and the interpretation of the tumor dose is highly sensitive to the imaging modality, PET enhancement metric, and threshold level used for tumor volume segmentation. The large variations in tumor doses clearly demonstrate the need for standard protocols for multimodality tumor segmentation in TRT dosimetry.

Figure 1:

Box plot comparing the tumor contour volumes for each threshold segmentation method. In general, TBR tumor volumes were larger (2.3 – 63.9 cc) than the SUV (0.1 – 34.7 cc) and MRI (0.4 – 11.8 cc) volumes. Because the smaller MRI contours were usually contained within the larger PET (SUV and TBR) contours, the MRI ∪ PET union volumes were generally similar to the PET-threshold contour volumes and the MRI ∩ PET intersection volumes/doses were similar to the MRI-threshold contour volumes.

Figure 2:

The MRI, 48 hr post injection ¹²⁴I-CLR1404 PET, and ¹³¹I-CLR1404 dose distributions for each patient. The MRI, SUV, and TBR threshold-based tumor contours and the resulting DVHs are also shown.

Figure 3:

DVHs of the union and intersection combination contours for the (a) TBR and (b) SUV thresholds for Patient 1. These are representative of the results seen in the rest of the patients where the doses within the TBR contours were typically smaller than the MRI contours because the TBR contours were larger in size and vice versa for the SUV contours. Additionally, the union contours were generally similar in size to the PET-based contour volumes so the DVHs based on the union contours were similar to the SUV/TBR DVHs. Conversely, the intersection contours were similar to the MRI-based contour volumes so the DVHs based the intersection contours were similar to the MRI DVHs.

Figure 4:

Mean tumor doses for each patient. The error bars represent the standard deviation. Note that the larger TBR contours (filled markers) generally had smaller mean doses and the smaller SUV contours (unfilled markers) generally had larger mean doses

Figure 5:

Correlation between the mean tumor dose and the tumor contour volumes for each patient. The Pearson correlation coefficient (R²) and p-values of the linear correlation are also shown.