131I-GD2-ch14.18 Scintigraphy to Evaluate Option for Radioimmunotherapy in Patients with Advanced Tumors.

The tumor-selective ganglioside antigene GD2 is frequently expressed on neuroblastomas and to a lesser extent on sarcomas and neuroendocrine tumors. The aim of our study was to evaluate the tumor targeting and biodistribution of 131I-labeled chimeric GD2-antibody clone 14/18 (131I-GD2-ch14.18) in patients with late-stage disease in order to identify eligibility for radioimmunotherapy. Methods: Twenty patients (neuroblastoma, n = 9; sarcoma, n = 9; pheochromocytoma, n = 1; and neuroendocrine tumor, n = 1) were involved in this study. A 21- to 131-MBq dose (1-2 MBq/kg) of 131I-GD2-ch14.18 (0.5-1.0 mg) was injected intravenously. Planar scintigraphy was performed within 1 h from injection (day 0) and on days 1, 2, 3, and 6 or 7 to analyze tumor uptake and tracer biodistribution. Serial blood samples were collected in 4 individuals. Absorbed dose to tumor lesions and organs was calculated using OLINDA software. Results: The tumor-targeting rate on a per-patient base was 65% (13/20), with 6 of 9 neuroblastomas showing uptake of 131I-GD2-ch14.18. Tumor lesions showed maximum uptake at 20-64 h after injection (effective half-life in tumors, 33-192 h). The tumor-absorbed dose varied between 0.52 and 30.2 mGy/MBq (median, 9.08 mGy/MBq; n = 13). Visual analysis showed prominent blood-pool activity up to day 2 or 3 after injection. No pronounced uptake was observed in the bone marrow compartment or in the kidneys. Bone marrow dose was calculated at 0.09-0.18 mGy/MBq (median, 0.12 mGy/MBq), whereas blood dose was 1.1-4.7 mGy/MBq. Two patients (1 neuroblastoma and 1 pheochromocytoma) with particularly high tumor uptake underwent radioimmunotherapy using 2.3 and 2.9 GBq of 131I-GD2-ch14.18, both achieving stable disease. Overall survival was 17 and 6 mo, respectively. Conclusion:131I-GD2-ch14.18 is cleared slowly from blood, not resulting in good tumor-to-background contrast until 2 d after application. With acceptable red marrow and organ dose, radioimmunotherapy is an option for patients with high tumor uptake. However, because of the variable GD2 expression, the decision should depend on pretherapeutic dosimetry.

The Prognostic Value of Quantitative Bone SPECT/CT Before 223Ra Treatment in Metastatic Castration-Resistant Prostate Cancer.

Radiolabeled bisphosphonates such as 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) typically show intense uptake in skeletal metastases from metastatic castration-resistant prostate cancer (mCRPC). Extensive bone involvement is regarded as a risk factor for mCRPC patients treated with 223Ra-dichloride (223Ra). The aim of this study was to quantify 99mTc-DPD uptake by means of SPECT/CT before 223Ra and compare the results with the feasibility of treatment and overall survival (OS). Methods: Sixty consecutive mCRPC patients were prospectively included in this study. SPECT/CT of the central skeleton covering the skull to the mid-femoral level was performed before the first cycle of 223Ra. The bone compartment was defined by means of low-dose CT. Emission data were corrected for scatter, attenuation, and decay supplemented by resolution recovery using dedicated software. The Kaplan-Meier estimator, U test, and Cox regression analysis were used for statistics. Results: Total 99mTc-DPD uptake of the central skeleton varied between 11% and 56% of injected dose (%ID) or between 1.8 and 10.5 %ID/1,000 mL of bone volume (%ID/L). SUVmean ranged from 1.9 to 7.4, whereas the SUVmax range was 18-248. Patients unable to complete 223Ra treatment because of progression and/or cytopenia (n = 23) showed significantly higher uptake (31.9 vs. 25.4 %ID and 6.0 vs. 4.7 %ID/L; P < 0.02). OS after 223Ra (median, 15.2 mo) was reduced to 7.3 mo in cases of skeletal uptake that was 26 %ID or higher, as compared with 30.8 mo if lower than 26 %ID (P = 0.008). Similar results were obtained for %ID/L and SUVmean SUVmax did not correlate with survival. %ID/L was identified as an independent prognostic factor for OS (hazard ratio, 1.381 per unit), along with number of previous treatment lines. Conclusion: Quantitative SPECT/CT of bone scans performed at baseline is prognostic for survival in mCRPC patients treated with 223Ra.

Influence of 99m-Tc-Nanocolloid Activity Concentration on Sentinel Lymph Node Detection in Endometrial Cancer: A Quantitative SPECT/CT Study.

This study evaluates quantitative combined single photon emission tomography/computed x-ray tomography (SPECT/CT) to assess the influence of radiotracer concentration on detection of sentinel lymph nodes (SLN) in endometrial cancer (EC). Eighty EC patients underwent pericervical 99m-Tc-nanocolloid injection followed by SPECT/CT. The subgroup of patients with failed SLN detection in SPECT/CT (n = 20) was compared to match-paired patients showing at least two SLNs. Results of intraoperative gamma probe measurements and quantitative SPECT/CT were used for comparison. In patients with detection failure, the percentage of injected dose, absolute activity, and volume of the injection site were significantly lower (30 ± 24% vs. 55 ± 19%; p = 0.01, 43 ± 36 MBq vs. 73 ± 33 MBq; p = 0.04, and 183 ± 164 mL vs. 266 ± 164 mL; p = 0.03) while mean activity concentration in liver, spleen, and bone marrow was significantly higher (p = 0.02). Activity concentration (>33 KBq/mL) and absolute activity (>73 MBq) of injection areas correlated with successful intraoperative SLN detection. In a subgroup of 19 SLNs, a correlation between SPECT/CT-derived uptake and intraoperative count rate was found (R2 = 0.8; p < 0.001). SLN detection in EC patients depended on high radiotracer activity at the cervical injection site. Quantitative SPECT/CT could predict successful intraoperative SLN detection and may help to optimize injection technique.

A Prospective Study of Quantitative SPECT/CT for Evaluation of Lung Shunt Fraction Before SIRT of Liver Tumors.

The lung shunt fraction (LSF) is estimated using 99mTc-macroaggregated albumin (99mTc-MAA) imaging before selective internal radiotherapy (SIRT) of the liver to reduce the risk of pulmonary irradiation. Generally, planar scans are acquired after injection of 99mTc-MAA into the hepatic artery. However, the validity of this approach is limited by differences in attenuation between liver and lung tissue as well as inaccurate segmentation of the organs. The aim of this study was to evaluate quantitative SPECT/CT for LSF assessment in a prospective clinical cohort. Methods: Fifty consecutive patients intended to undergo SIRT were imaged within 1 h after injection of 99mTc-MAA using a SPECT/CT γ-camera. Planar scans of the lung and liver region were acquired in anterior and posterior views, followed by SPECT/CT scans of the thorax and abdomen. Emission data were corrected for scatter, attenuation, and resolution recovery using dedicated software. To quantify the radioactivity concentration in the lung, liver, urinary bladder and remainder of the thoracoabdominal body, volumes of interest were defined on the SPECT/CT images. 99mTc-MAA concentrations were calculated as percentage injected dose (%ID). Results: Mean 99mTc-MAA uptake in liver and lung accounted for only 79 %ID, whereas 13.1 %ID was present in the remainder of the body. In all patients, LSF as calculated from planar scans accounted for a median of 6.8% (range, 3.4%-32.3%), whereas the SPECT/CT quantitation revealed significantly lower LSF estimates, at a median of 1.9% (range, 0.8%-15.7%) (P < 0.0001, Wilcoxon test). On the basis of planar imaging, dose reduction or even contraindications to SIRT had to be considered in 10 of 50 patients, as their LSF was calculated at 10% or more. In contrast, SPECT/CT quantitation showed substantial shunting in only 2 of the 50 patients. Conclusion: Quantitative SPECT/CT reveals that the LSF is considerably lower than shown on planar imaging. Thus, the resulting dose to the lung parenchyma may be less than conventionally assumed. However, the safety of the SPECT/CT-derived dose range will have to be evaluated.

Improving CT-Based PET Attenuation Correction in the Vicinity of Metal Implants by an Iterative Metal Artifact Reduction Algorithm of CT Data and Its Comparison to Dual-Energy-Based Strategies: A Phantom Study.

OBJECTIVE: The aim of this study was to evaluate the potential of iterative metal artifact reduction (IMAR) for the improvement of computed tomography (CT)-based position emission tomography (PET) attenuation correction in the vicinity of metal implants and compare it with dual-energy-based metal artifact reduction strategies. METHODS: A dedicated dental phantom was constructed consisting of a cylindrical tube filled with [18-F]FDG solution (5300 mL and 50.9 MBq) containing 2 artificial jaws with 1 nonprecious alloy fixed dental prosthesis and 3 single tooth crowns in the lower jaw.Computed tomography measurements of the phantom were acquired on a stand-alone dual-energy CT scanner equipped with IMAR capabilities. A series of 24 CT data sets were obtained using different scan parameters and monoenergetic extrapolation of dual-energy CT acquisitions with and without IMAR reconstruction.Position emission tomography measurements of the phantom were performed on a state-of-art PET/CT scanner. Position emission tomography data were reconstructed using all 24 previously acquired CT data sets.Relative errors in the quantification of activity concentrations using the different CT scanning and reconstruction parameters were quantified by placement of regions of interest within the phantom. RESULTS: Metal artifacts of different extent were observed in all CT data sets. A marked reduction in CT metal artifacts was observed using IMAR. In general, activity concentrations were overestimated/underestimated in areas of high/low-density metal artifacts, respectively.Relative errors in PET quantification ranged between -71% and +70% without IMAR. Using IMAR, these errors were reduced to a range between -40% and +12%. Averaged absolute values of relative PET quantification errors were 27% and 7% without and with the use of IMAR (P < 0.001), respectively. Iterative metal artifact reduction was superior compared with dual-energy-based metal artifact reduction strategies, and the combination of both strategies did not result in further significant improvement of PET quantification. CONCLUSIONS: The use of IMAR in PET/CT is a promising approach for markedly improving image quality and PET quantification in the vicinity of metal implants. Further clinical studies are necessary to assess the clinical performance of this algorithm in patients.