Dataset Information

Comparison Between Diffusion-Weighted MRI and ¹²³ I-mIBG Uptake in Primary High-Risk Neuroblastoma.

ABSTRACT:

Background

High-risk neuroblastoma (HR-NB) has a variable response to preoperative chemotherapy. It is not possible to differentiate viable vs. nonviable residual tumor before surgery.

Purpose

To explore the association between apparent diffusion coefficient (ADC) values from diffusion-weighted magnetic resonance imaging (DW-MRI), ¹²³ I-meta-iodobenzyl-guanidine (¹²³ I-mIBG) uptake, and histology before and after chemotherapy.

Study type

Retrospective.

Subjects

Forty patients with HR-NB.

Field strength/sequence

1.5T axial DW-MRI (b = 0,1000 s/mm² ) and T₂ -weighted sequences. ¹²³ I-mIBG scintigraphy planar imaging (all patients), with additional ¹²³ I-mIBG single-photon emission computed tomography / computerized tomography (SPECT/CT) imaging (15 patients).

Assessment

ADC maps and ¹²³ I-mIBG SPECT/CT images were coregistered to the T₂ -weighted images. ¹²³ I-mIBG uptake was normalized with a tumor-to-liver count ratio (TLCR). Regions of interest (ROIs) for primary tumor volume and different intratumor subregions were drawn. The lower quartile ADC value (ADC_25prc ) was used over the entire tumor volume and the overall level of ¹²³ I-mIBG uptake was graded into avidity groups.

Statistical tests

Analysis of variance (ANOVA) and linear regression were used to compare ADC and MIBG values before and after treatment. Threshold values to classify tumors as viable/necrotic were obtained using ROC analysis of ADC and TLCR values.

Results

No significant difference in whole-tumor ADC_25prc values were found between different ¹²³ I-mIBG avidity groups pre- (P = 0.31) or postchemotherapy (P = 0.35). In the "intratumor" analysis, 5/15 patients (prechemotherapy) and 0/14 patients (postchemotherapy) showed a significant correlation between ADC and TLCR values (P < 0.05). Increased tumor shrinkage was associated with lower pretreatment tumor ADC_25prc values (P < 0.001); no association was found with pretreatment ¹²³ I-mIBG avidity (P = 0.17). Completely nonviable tumors had significantly lower postchemotherapy ADC_25prc values than tumors with >10% viable tumor (P < 0.05). Both pre- and posttreatment TLCR values were significantly higher in patients with >50% viable tumor than those with 10-50% viable tumor (P < 0.05). DATA CONCLUSION: ¹²³ I-mIBG avidity and ADC values are complementary noninvasive biomarkers of therapeutic response in HR-NB.

Level of evidence

Technical efficacy stage

SUBMITTER: Privitera L

PROVIDER: S-EPMC8246892 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe therapeutic use of [131I]meta-iodobenzylguanidine ([131I]MIBG) is often accompanied by hematological toxicity, mainly consisting of persistent and severe thrombocytopenia. While MIBG accumulates in neuroblastoma cells via selective uptake by the norepinephrine transporter (NET), the serotonin transporter (SERT) is responsible for cellular uptake of MIBG in platelets. In this study, we have investigated whether pharmacological intervention with selective serotonin reuptake inhibitors (SSRIs) may prevent radiotoxic MIBG uptake in platelets without affecting neuroblastoma tumor uptake.MethodsTo determine the transport kinetics of SERT for [125I]MIBG, HEK293 cells were transfected with SERT and uptake assays were conducted. Next, a panel of seven SSRIs was tested in vitro for their inhibitory potency on the uptake of [125I]MIBG in isolated human platelets and in cultured neuroblastoma cells. We investigated in vivo the efficacy of the four best performing SSRIs on the accumulation of [125I]MIBG in nude mice bearing subcutaneous neuroblastoma xenografts. In ex vivo experiments, the diluted plasma of mice treated with SSRIs was added to isolated human platelets to assess the effect on [125I]MIBG uptake.ResultsSERT performed as a low-affinity transporter of [125I]MIBG in comparison with NET (Km = 9.7??M and 0.49??M, respectively). Paroxetine was the most potent uptake inhibitor of both serotonin (IC50 = 0.6?nM) and MIBG (IC50 = 0.2?nM) in platelets. Citalopram was the most selective SERT inhibitor of [125I]MIBG uptake, with high SERT affinity in platelets (IC50 = 7.8?nM) and low NET affinity in neuroblastoma cells (IC50 = 11.940?nM). The in vivo tested SSRIs (citalopram, fluvoxamine, sertraline, and paroxetine) had no effect on [125I]MIBG uptake levels in neuroblastoma xenografts. In contrast, treatment with desipramine, a NET selective inhibitor, resulted in profoundly decreased xenograft [125I]MIBG levels (p < 0.0001). In ex vivo [125I]MIBG uptake experiments, 100- and 34-fold diluted murine plasma of mice treated with citalopram added to isolated human platelets led to a decrease in MIBG uptake of 54-76%, respectively.ConclusionOur study demonstrates for the first time that SSRIs selectively inhibit MIBG uptake in platelets without affecting MIBG accumulation in an in vivo neuroblastoma model. The concomitant application of citalopram during [131I]MIBG therapy seems a promising strategy to prevent thrombocytopenia in neuroblastoma patients.

Project description:Background Diffusion-weighted imaging (DWI) shows promise in detecting and monitoring breast cancer, but standard spin-echo (SE) echo-planar DWI methods often have poor image quality and low spatial resolution. Proposed alternatives include readout-segmented (RS) echo-planar imaging and axially reformatted (AR)-simultaneous multislice (SMS) imaging. Purpose To compare the resolution and image quality of standard SE echo-planar imaging DWI with two high-spatial-resolution alternatives, RS echo-planar and AR-SMS imaging, for breast imaging. Materials and Methods In a prospective study (2016-2018), three 5-minute DWI protocols were acquired at 3.0 T, including standard SE echo-planar imaging, RS echo-planar imaging with five segments, and AR-SMS imaging with four times slice acceleration. Participants were women undergoing breast MRI either as part of a treatment response clinical trial or undergoing breast MRI for screening or suspected cancer. A commercial breast phantom was imaged for resolution comparison. Three breast radiologists reviewed images in random order, including clinical images indicating the lesion, images with b value of 800 sec/mm2, and apparent diffusion coefficient (ADC) maps from the three randomly labeled DWI methods. Readers measured the longest dimension and lesion-average ADC on three DWI methods, reported measurement confidence, and rated or ranked the quality of each image. The scores were fit to a linear mixed-effects model with intercepts for reader and subject. Results The smallest feature (1 mm) was only detectible in a phantom on images from AR-SMS DWI. Thirty lesions from 28 women (mean age, 50 years ± 13 [standard deviation]) were evaluated. On the five-point Likert scale for image quality, AR-SMS imaging scored 1.31 points higher than SE echo-planar imaging and 0.74 points higher than RS echo-planar imaging, whereas RS echo-planar imaging scored 0.57 points higher than SE echo-planar imaging (all P < .001). Conclusion The axially reformatted simultaneous multislice protocol was rated highest for image quality, followed by the readout-segmented echo-planar imaging protocol. Both were rated higher than the standard spin-echo echo-planar imaging. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Partridge in this issue.

Dataset Information

Comparison Between Diffusion-Weighted MRI and ¹²³ I-mIBG Uptake in Primary High-Risk Neuroblastoma.

Background

Purpose

Study type

Subjects

Field strength/sequence

Assessment

Statistical tests

Results

Level of evidence

Technical efficacy stage

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Comparison Between Diffusion-Weighted MRI and 123 I-mIBG Uptake in Primary High-Risk Neuroblastoma.

Background

Purpose

Study type

Subjects

Field strength/sequence

Assessment

Statistical tests

Results

Level of evidence

Technical efficacy stage

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Comparison Between Diffusion-Weighted MRI and ¹²³ I-mIBG Uptake in Primary High-Risk Neuroblastoma.