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Background: Prior studies suggest that norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT2) mediate meta-iodobenzylguanidine (MIBG) uptake and retention in neuroblastoma tumors. We evaluated the relationship between NET and VMAT2 tumor expression and clinical response to 131 I-MIBG therapy in patients with neuroblastoma., Methods: Immunohistochemistry (IHC) was used to evaluate NET and VMAT2 protein expression levels on archival tumor samples (obtained at diagnosis or relapse) from patients with relapsed or refractory neuroblastoma treated with 131 I-MIBG. A composite protein expression H-score was determined by multiplying a semi-quantitative intensity value (0-3+) by the percentage of tumor cells expressing the protein., Results: Tumor samples and clinical data were available for 106 patients, of whom 28.3% had partial response (PR) or higher. NET H-score was not significantly associated with response (≥PR), though the percentage of tumor cells expressing NET was lower among responders (median 80% for ≥PR vs. 90% for 131 I-MIBG therapy in patients with relapsed/refractory neuroblastoma. Increased VMAT2 protein expression is associated with a more differentiated disease phenotype., (© 2023 Wiley Periodicals LLC.)

The metaiodobenzylguanidine (MIBG) scan is one of the most sensitive noninvasive lesion detection modalities for neuroblastoma. Unlike 123 I-MIBG, 124 I-MIBG allows high-resolution PET. We evaluated 124 I-MIBG PET/CT for its diagnostic performance as directly compared with paired 123 I-MIBG scans. Methods: Before 131 I-MIBG therapy, standard 123 I-MIBG imaging (5.2 MBq/kg) was performed on 7 patients, including whole-body (anterior-posterior) planar imaging, focused-field-of-view SPECT/CT, and whole-body 124 I-MIBG PET/CT (1.05 MBq/kg). After therapy, 2 of 7 patients also completed 124 I-MIBG PET/CT as well as paired 123 I-MIBG planar imaging and SPECT/CT. One patient underwent 124 I-MIBG PET/CT only after therapy. We evaluated all 8 patients who showed at least 1 123 I-MIBG-positive lesion with a total of 10 scans. In 8 pairs, 123 I-MIBG and 124 I-MIBG were performed within 1 mo of each other. The locations of identified lesions, the number of total lesions, and the curie scores were recorded for the 123 I-MIBG and 124 I-MIBG scans. Finally, for 5 patients who completed at least 3 PET/CT scans after administration of 124 I-MIBG, we estimated the effective dose of 124 I-MIBG. Results: 123 I-MIBG whole-body planar scans, focused-field-of-view SPECT/CT scans, and whole-body 124 I-MIBG PET scans found 25, 32, and 87 total lesions, respectively. There was a statistically significant difference in lesion detection for 124 I-MIBG PET/CT versus 123 I-MIBG planar imaging ( P < 0.0001) and 123 I-MIBG SPECT/CT ( P < 0.0001). The curie scores were also higher for 124 I-MIBG PET/CT than for 123 I-MIBG planar imaging and SPECT/CT in 6 of 10 patients. 124 I-MIBG PET/CT demonstrated better detection of lesions throughout the body, including the chest, spine, head and neck, and extremities. The effective dose estimated for patient-specific 124 I-MIBG was approximately 10 times that of 123 I-MIBG; however, given that we administered a very low activity of 124 I-MIBG (1.05 MBq/kg), the effective dose was only approximately twice that of 123 I-MIBG despite the large difference in half-lives (100 vs. 13.2 h). Conclusion: The first-in-humans use of low-dose 124 I-MIBG PET for monitoring disease burden demonstrated tumor detection capability superior to that of 123 I-MIBG planar imaging and SPECT/CT., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: Radiation dose calculated on tumors for radiopharmaceutical therapy varies significantly from tumor to tumor and from patient to patient. Accurate estimation of radiation dose requires multiple time point measurements using radionuclide imaging modalities such as SPECT or PET. In this report, we show our technical development of reducing the number of scans needed for reasonable estimation of tumor and normal organ dose in our pretherapy imaging and dosimetry platform of 124 I-metaiodobenzylguanidine (MIBG) positron emission tomography/computed tomography (PET/CT) for 131 I-MIBG therapy of neuroblastoma., Methods: We analyzed the simplest kinetic data, areas of two-time point data for five patients with neuroblastoma who underwent 3 or 4 times of 124 I-MIBG PET/CT scan prior to 131 I-MIBG therapy. The data for which we derived areas were percent of injected activity (%IA) and standardized uptake value of tumors. These areas were correlated with time-integrated activity coefficients (TIACs) from full data (3 or 4 time points). TIACs are direct correlates with radiation dose as long as the volume and the radionuclide are known., Results: The areas of %IAs between data obtained from all the two-time points with time points 1 and 2 (day 0 and day 1), time points 2 and 3 (day 1 and day 2), and time points 1 and 3 (day 0 and day 2) showed reasonable correlation (Pearson's correlation coefficient |r| > 0.5) with not only tumor and organ TIACs but also tumor and organ absorbed doses. The tumor and organ doses calculated using %IA areas of time point 1 and time point 2 were our best fits at about 20% individual percent difference compared to doses calculated using 3 or 4 time points., Conclusions: We could achieve reasonable accuracy of estimating tumor doses for subsequent radiopharmaceutical therapy using only the two-time point imaging sessions. Images obtained from these time points (within the 48-h after administration of radiopharmaceutical) were also viewed as useful for diagnostic reading. Although our analysis was specific to 124 I-MIBG PET/CT pretherapy imaging data for 131 I-MIBG therapy of neuroblastoma and the number of imaging datasets was not large, this feasible methodology would generally be applicable to other imaging and therapeutic radionuclides with an appropriate data analysis similar to our analysis to other imaging and therapeutic radiopharmaceuticals., (© 2019 American Association of Physicists in Medicine.)

Several reports of second malignant neoplasm (SMN) in patients with relapsed neuroblastoma after treatment with (131)I-MIBG suggest the possibility of increased risk. Incidence of and risk factors for SMN after (131)I-MIBG have not been defined. This is a multi-institutional retrospective review of patients with neuroblastoma treated with (131)I-MIBG therapy. A competing risk approach was used to calculate the cumulative incidence of SMN from time of first exposure to (131)I-MIBG. A competing risk regression was used to identify potential risk factors for SMN. The analytical cohort included 644 patients treated with (131)I-MIBG. The cumulative incidence of SMN was 7.6% (95% confidence interval [CI], 4.4-13.0%) and 14.3% (95% CI, 8.3-23.9%) at 5 and 10 years from first (131)I-MIBG, respectively. No increase in SMN risk was found with increased number of (131)I-MIBG treatments or higher cumulative activity per kilogram of (131)I-MIBG received (p = 0.72 and p = 0.84, respectively). Thirteen of the 19 reported SMN were haematologic. In a multivariate analysis controlling for variables with p < 0.1 (stage, age at first (131)I-MIBG, bone disease, disease status at time of first (131)I-MIBG), patients with relapsed/progressive disease had significantly lower risk of SMN (subdistribution hazard ratio 0.3, 95% CI, 0.1-0.8, p = 0.023) compared to patients with persistent/refractory neuroblastoma. The cumulative risk of SMN after (131)I-MIBG therapy for patients with relapsed or refractory neuroblastoma is similar to the greatest published incidence for high-risk neuroblastoma after myeloablative therapy, with no dose-dependent increase. As the number of patients treated and length of follow-up time increase, it will be important to reassess this risk., (Copyright © 2016 Elsevier Ltd. All rights reserved.)