Anatomic patterns of relapse and progression following treatment with 131 I-MIBG in relapsed or refractory neuroblastoma.

OBJECTIVES: Patients with metaiodobenzylguanidine (MIBG)-avid relapsed or refractory neuroblastoma after initial therapy may exhibit transient responses to salvage treatment with iodine-131 metaiodobenzylguanidine (131 I-MIBG). It is unclear whether disease progression following 131 I-MIBG treatment occurs in previously involved versus new anatomic sites of disease. Understanding this pattern of relapse will inform the use of consolidation therapy following 131 I-MIBG administration. METHODS: Patients with relapsed or refractory metastatic MIBG-avid neuroblastoma or ganglioneuroblastoma, who received single-agent 131 I-MIBG, had stable or responding disease 6-8 weeks following 131 I-MIBG, but subsequently experienced disease progression were included. MIBG scans were reviewed to establish anatomic and temporal evolution of MIBG-avid disease. RESULTS: A total of 84 MIBG-avid metastatic sites were identified immediately prior to MIBG therapy in a cohort of 12 patients. At first progression, a total of 101 MIBG-avid sites were identified, of which 69 (68%) overlapped with pre-treatment disease sites, while 32 (32%) represented anatomically new disease areas. Eight of 12 patients had one or more new MIBG-avid sites at first progression. Of the 69 involved sites at progression that overlapped with pre-treatment disease, 11 represented relapsed sites that had cleared following MIBG therapy, two were persistent but increasingly MIBG-avid, and 56 were stably persistent. CONCLUSIONS: Previously involved anatomic disease sites predominate at disease progression following 131 I-MIBG treatment. Nevertheless, the majority of patients progressed in at least one new anatomic disease site. This suggests that consolidation focal therapies targeting residual disease sites may be of limited benefit in preventing systemic disease progression following 131 I-MIBG treatment of relapsed or refractory neuroblastoma.

A Deep Learning Model to Predict a Diagnosis of Alzheimer Disease by Using 18F-FDG PET of the Brain.

Purpose To develop and validate a deep learning algorithm that predicts the final diagnosis of Alzheimer disease (AD), mild cognitive impairment, or neither at fluorine 18 (18F) fluorodeoxyglucose (FDG) PET of the brain and compare its performance to that of radiologic readers. Materials and Methods Prospective 18F-FDG PET brain images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (2109 imaging studies from 2005 to 2017, 1002 patients) and retrospective independent test set (40 imaging studies from 2006 to 2016, 40 patients) were collected. Final clinical diagnosis at follow-up was recorded. Convolutional neural network of InceptionV3 architecture was trained on 90% of ADNI data set and tested on the remaining 10%, as well as the independent test set, with performance compared to radiologic readers. Model was analyzed with sensitivity, specificity, receiver operating characteristic (ROC), saliency map, and t-distributed stochastic neighbor embedding. Results The algorithm achieved area under the ROC curve of 0.98 (95% confidence interval: 0.94, 1.00) when evaluated on predicting the final clinical diagnosis of AD in the independent test set (82% specificity at 100% sensitivity), an average of 75.8 months prior to the final diagnosis, which in ROC space outperformed reader performance (57% [four of seven] sensitivity, 91% [30 of 33] specificity; P < .05). Saliency map demonstrated attention to known areas of interest but with focus on the entire brain. Conclusion By using fluorine 18 fluorodeoxyglucose PET of the brain, a deep learning algorithm developed for early prediction of Alzheimer disease achieved 82% specificity at 100% sensitivity, an average of 75.8 months prior to the final diagnosis. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Larvie in this issue.

Predictors of response, progression-free survival, and overall survival using NANT Response Criteria (v1.0) in relapsed and refractory high-risk neuroblastoma.

PURPOSE: The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC) were developed to optimize response assessment in patients with recurrent/refractory neuroblastoma. Response predictors and associations of the NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were analyzed. METHODS: A retrospective analysis was performed of patients with recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase 1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie scoring), and percent bone marrow (BM) tumor (morphology). RESULTS: Fourteen (6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among 203 patients evaluable for response. Five-year progression-free survival (PFS) was 16 ± 3%; overall survival (OS) was 27 ± 3%. Disease sites at enrollment included MIBG-avid lesions (100% MIBG trials; 84% non-MIBG trials), measurable CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0 (P < 0.001), lower Curie score (P = 0.003), no measurable CT/MRI lesions (P = 0.044), and treatment on peripheral blood stem cell (PBSC) supported trials (P = 0.005) were associated with achieving CR/PR. Overall response of stable disease (SD) or better was associated with better OS (P < 0.001). In multivariable analysis, MYCN amplification (P = 0.037) was associated with worse PFS; measurable CT/MRI lesions (P = 0.041) were associated with worse OS; prior progressive disease (PD; P < 0.001/P < 0.001), Curie score ≥ 1 (P < 0.001; P = 0.001), higher Curie score (P = 0.048/0.037), and treatment on non-PBSC trials (P = < 0.001/0.003) were associated with worse PFS and OS. CONCLUSIONS: NANTRCv1.0 response of at least SD is associated with better OS in patients with recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict response and outcome. Identifying these variables can optimize Phase 1/2 trial design to select novel agents for further testing.

In Vivo PET Imaging of the Activated Immune Environment in a Small Animal Model of Inflammatory Arthritis.

BACKGROUND: Evolving immune-mediated therapeutic strategies for rheumatoid arthritis (RA) may benefit from an improved understanding of the complex role that T-cell activation plays in RA. This study assessed the potential of fluorine-18-labeled 9-ß-d-arabinofuranosylguanine ([18F]F-AraG) positron emission tomography (PET) imaging to report immune activation in vivo in an adjuvant-induced arthritis (AIA) small animal model. METHODS: Using positron emission tomography-computed tomography imaging, uptake of [18F]F-AraG in the paws of mice affected by arthritis at 6 (acute) and 20 (chronic) days following AIA induction in a single paw was assessed and compared to uptake in contralateral control paws. Fractions of T cells and B cells demonstrating markers of activation at the 2 time points were determined by flow cytometry. RESULTS: Differential uptake of [18F]F-AraG was demonstrated on imaging of the affected joint when compared to control at both acute and chronic time points with corresponding changes in markers of T-cell activation observed on flow cytometry. CONCLUSION: [18F]F-AraG may serve as an imaging biomarker of T-cell activation in inflammatory arthritis. Further development of this technique is warranted and could offer a tool to explore the temporal link between activated T cells and RA as well as to monitor immune-mediated therapies for RA in clinical trials.

Effect of Time-of-Flight and Regularized Reconstructions on Quantitative Measurements and Qualitative Assessments in Newly Diagnosed Prostate Cancer With 18F-Fluorocholine Dual Time Point PET/MRI.

Recent technical advances in positron emission tomography/magnetic resonance imaging (PET/MRI) technology allow much improved time-of-flight (TOF) and regularized iterative PET reconstruction regularized iterative reconstruction (RIR) algorithms. We evaluated the effect of TOF and RIR on standardized uptake values (maximum and peak SUV [SUVmax and SUVpeak]) and their metabolic tumor volume dependencies and visual image quality for 18F-fluorocholine PET/MRI in patients with newly diagnosed prostate cancer. Fourteen patients were administered with 3 MBq/kg of 18F-fluorocholine and scanned dynamically for 30 minutes. Positron emission tomography images were divided to early and late time points (1-6 minutes summed and 7-30 minutes summed). The values of the different SUVs were documented for dominant PET-avid lesions, and metabolic tumor volume was estimated using a 50% isocontour and SUV threshold of 2.5. Image quality was assessed via visual acuity scoring (VAS). We found that incorporation of TOF or RIR increased lesion SUVs. The lesion to background ratio was not improved by TOF reconstruction, while RIR improved the lesion to background ratio significantly ( P < .05). The values of the different VAS were all significantly higher ( P < .05) for RIR images over TOF, RIR over non-TOF, and TOF over non-TOF. In conclusion, our data indicate that TOF or RIR should be incorporated into current protocols when available.

Ictal lack of binding to brain parenchyma suggests integrity of the blood-brain barrier for 11C-dihydroergotamine during glyceryl trinitrate-induced migraine.

SEE DREIER DOI 101093/AWW112 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: For many decades a breakdown of the blood-brain barrier has been postulated to occur in migraine. Hypothetically this would facilitate access of medications, such as dihydroergotamine or triptans, to the brain despite physical properties otherwise restricting their entry. We studied the permeability of the blood-brain barrier in six migraineurs and six control subjects at rest and during acute glyceryl trinitrate-induced migraine attacks using positron emission tomography with the novel radioligand (11)C-dihydroergotamine, which is chemically identical to pharmacologically active dihydroergotamine. The influx rate constant Ki, average dynamic image and time activity curve were assessed using arterial blood sampling and served as measures for receptor binding and thus blood-brain barrier penetration. At rest, there was binding of (11)C-dihydroergotamine in the choroid plexus, pituitary gland, and venous sinuses as expected from the pharmacology of dihydroergotamine. However, there was no binding to the brain parenchyma, including the hippocampus, the area with the highest density of the highest-affinity dihydroergotamine receptors, and the raphe nuclei, a postulated brainstem site of action during migraine, suggesting that dihydroergotamine is not able to cross the blood-brain barrier. This binding pattern was identical in migraineurs during glyceryl trinitrate-induced migraine attacks as well as in matched control subjects. We conclude that (11)C-dihydroergotamine is unable to cross the blood-brain barrier interictally or ictally demonstrating that the blood-brain barrier remains tight for dihydroergotamine during acute glyceryl trinitrate-induced migraine attacks.

The utility of radioisotope cisternography in low CSF/volume syndromes compared to myelography.

Objective The objective of this report is to compare computed tomography (CT) and magnetic resonance (MR) myelography with radioisotope cisternography (RC) for detection of spinal cerebrospinal (CSF) leaks. Methods We retrospectively reviewed 12 spontaneous intracranial hypotension (SIH) patients; CT and RC were performed simultaneously. Three patients had MR myelography. Results CT and/or MR myelography identified CSF leaks in four of 12 patients. RC detected spinal leaks in all three patients confirmed by CT myelography; RC identified the CSF leak location in two of three cases, and these were due to osteophytic spicules and/or discs. RC showed only enlarged perineural activity. Only intrathecal gadolinium MR myelography clearly identified a slow leak from a perineural cyst. In eight remaining cases, the leak site was unknown; however, two of these showed indirect signs of CSF leak on RC. CSF slow leaks from perineural cysts were the most common presumed etiology; and the cysts were best visualized on myelography. Conclusion RC is comparable to CT myelography but has spatial limitations and should be limited to atypical cases.

Impact of Whole-Body Radiation Dose on Response and Toxicity in Patients With Neuroblastoma After Therapy With 131 I-Metaiodobenzylguanidine (MIBG).

BACKGROUND: (131) I-metaiodobenzylguanidine ((131) I-MIBG) is a targeted radiopharmaceutical for patients with neuroblastoma. Despite its tumor-specific uptake, the treatment with (131) I-MIBG results in whole-body radiation exposure. Our aim was to correlate whole-body radiation dose (WBD) from (131) I-MIBG with tumor response, toxicities, and other clinical factors. METHODS: This retrospective cohort analysis included 213 patients with high-risk neuroblastoma treated with (131) I-MIBG at UCSF Benioff Children's Hospital between 1996 and 2015. WBD was determined from radiation exposure rate measurements. The relationship between WBD ordered tertiles and variables were analyzed using Cochran-Mantel-Haenszel test of trend, Kruskal-Wallis test, and one-way analysis of variance. Correlation between WBD and continuous variables was analyzed using Pearson correlation and Spearman rank correlation. RESULTS: WBD correlated with (131) I-MIBG administered activity, particularly with (131) I-MIBG per kilogram (P < 0.001). Overall response rate did not differ significantly among the three tertiles of WBD. Correlation between response by relative Curie score and WBD was of borderline significance, with patients receiving a lower WBD showing greater reduction in osteomedullary metastases by Curie score (rs = 0.16, P = 0.049). There were no significant ordered trends among tertiles in any toxicity measures (grade 4 neutropenia, thrombocytopenia < 20,000/µl, and grade > 1 hypothyroidism). CONCLUSIONS: This study showed that (131) I-MIBG activity per kilogram correlates with WBD and suggests that activity per kilogram will predict WBD in most patients. Within the range of activities prescribed, there was no correlation between WBD and either response or toxicity. Future studies should evaluate tumor dosimetry, rather than just WBD, as a tool for predicting response following therapy with (131) I-MIBG.

Bone remodeling after MR imaging-guided high-intensity focused ultrasound ablation: evaluation with MR imaging, CT, Na(18)F-PET, and histopathologic examination in a swine model.

PURPOSE: To serially monitor bone remodeling in the swine femur after magnetic resonance (MR) imaging-guided high-intensity focused ultrasound (HIFU) ablation with MR imaging, computed tomography (CT), sodium fluorine 18 (Na(18)F)-positron emission tomography (PET), and histopathologic examination, as a function of sonication energy. MATERIALS AND METHODS: Experimental procedures received approval from the local institutional animal care and use committee. MR imaging-guided HIFU was used to create distal and proximal ablations in the right femurs of eight pigs. The energy used at the distal target was higher (mean, 419 J; range, 390-440 J) than that used at the proximal target (mean, 324 J; range, 300-360 J). Imaging was performed before and after ablation with 3.0-T MR imaging and 64-section CT. Animals were reevaluated at 3 and 6 weeks with MR imaging (n = 8), CT (n = 8), Na(18)F-PET (n = 4), and histopathologic examination (n = 4). Three-dimensional ablation lengths were measured on contrast material-enhanced MR images, and bone remodeling in the cortex was measured on CT images. RESULTS: Ablation sizes at MR imaging 3 and 6 weeks after MR imaging-guided HIFU ablation were similar between proximal (low-energy) and distal (high-energy) lesions (average, 8.7 × 21.9 × 16.4 mm). However, distal ablation lesions (n = 8) demonstrated evidence of subperiosteal new bone formation at CT, with a subtle focus of new ossification at 3 weeks and a larger focus of ossification at 6 weeks. New bone formation was associated with increased uptake at Na(18)F-PET in three of four animals; this was confirmed at histopathologic examination in four of four animals. CONCLUSION: MR imaging-guided HIFU ablation of bone may result in progressive remodeling, with both subcortical necrosis and subperiosteal new bone formation. This may be related to the use of high energies. MR imaging, CT, and PET are suitable noninvasive techniques to monitor bone remodeling after MR imaging-guided HIFU ablation.

Triple-negative and non-triple-negative invasive breast cancer: association between MR and fluorine 18 fluorodeoxyglucose PET imaging.

PURPOSE: To assess the relationship between parameters measured on dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in primary invasive breast cancer. MATERIALS AND METHODS: This HIPAA-compliant study was a retrospective review of medical records and therefore approved by the institutional review board without the requirement for informed consent. Patients with a diagnosis of invasive breast cancer from January 2005 through December 2009 who underwent both DCE MR imaging and FDG PET/CT before treatment initiation were retrospectively identified. Fractional volumes were measured for ranges of signal enhancement ratio (SER) values from DCE MR imaging data and compared with maximum standardized uptake values (SUVmax) from FDG PET/CT data. Linear regression analysis was performed to clarify the relationship between SER and SUVmax, adjusting for tumor size, pathologic grade, and receptor status. RESULTS: Analyzed were 117 invasive breast cancers in 117 patients. Overall, a higher percentage of high washout kinetics was positively associated with SUVmax (1.57% increase in SUVmax per 1% increase in high washout; P = .020), and a higher percentage of low plateau kinetics was negatively associated with SUVmax (1.19% decrease in SUVmax per 1% increase in low plateau; P = .003). These relationships were strongest among triple-negative (TN) tumors (4.34% increase in SUVmax per 1% increase in high washout and 2.65% decrease in SUVmax per 1% increase in low plateau; P = .018 and .004, respectively). CONCLUSION: In invasive breast carcinoma, there is a positive relationship between the percentage of high washout and SUVmax and a negative relationship between the percentage of low plateau and SUVmax. These results are stronger in TN tumors. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130058/-/DC1.

Acute changes in blood pressure in patients with neuroblastoma treated with ¹³¹I-metaiodobenzylguanidine (MIBG).

BACKGROUND: Iodine-131-metaiodobenzylguanidine ((131)I-MIBG) provides targeted radiotherapy for children with neuroblastoma. The aim of our study was to evaluate systematically the acute effects of (131)I-MIBG on blood pressure in patients with neuroblastoma and to identify possible predictors of hypertension. PROCEDURE: We conducted a retrospective chart review of neuroblastoma patients who were treated with (131)I-MIBG between January 1, 1999 and June 1, 2012 at the University of California, San Francisco. Clinical data for 172 patients with neuroblastoma, receiving 218 administrations of (131)I-MIBG, were collected. The primary endpoint was development of systolic blood pressure above the 95th percentile for age. Logistic regression with generalized estimating equations to account for multiple administrations in some subjects was used to identify bivariate and multivariate predictors of hypertension. RESULTS: Of the 218 administrations of (131)I-MIBG, 112 (51.3%) were associated with at least one episode of systolic hypertension during or after the (131)I-MIBG infusion. The majority of these acute elevations in blood pressure resolved within 48 hours of the infusion. Only six administrations in five patients required nifedipine administration to lower blood pressure. Younger age (P = 0.012), lower eGFR (P = 0.047), and elevated blood pressure measurements immediately before infusion began (P = 0.010) were all independently associated with risk of treatment-associated hypertension. CONCLUSIONS: Acute elevations in blood pressure are common after therapeutic doses of (131) I-MIBG. Elevations in blood pressure typically occur only within the first 48 hours after (131)I-MIBG administration. Blood pressure monitoring during this period of risk is recommended.

Differentiation of normal thymus from anterior mediastinal lymphoma and lymphoma recurrence at pediatric PET/CT.

PURPOSE: To evaluate the role of positron emission tomography (PET)/computed tomography (CT) in the differentiation of normal thymus from mediastinal lymphoma and lymphoma recurrence in pediatric patients. MATERIALS AND METHODS: The study was approved by the institutional review board, and informed consent was waived. The study was HIPAA compliant. Two hundred eighty-two fluorine 18 fluorodeoxyglucose PET/CT studies in 75 pediatric oncology patients were reviewed retrospectively. Patients were divided into four groups: anterior mediastinal lymphoma (group A, n=16), anterior mediastinal lymphoma with subsequent recurrence (group B, n=5), lymphoma outside the mediastinum (group C, n=16), and other malignant tumors outside the thymus (group D, n=38). Analyses included measurements of the maximum anteroposterior and transverse dimensions of the anterior mediastinal mass or thymus on axial CT images and measurements of maximum standardized uptake values of anterior mediastinal mass, thymus (SUVt), and bone marrow at the level of the fifth lumbar vertebra (SUVb) on PET images. Quantitative parameters were compared by using an analysis of variance test. RESULTS: Mean prechemotherapy SUVt was 4.82 for group A, 8.45 for group B, 2.00 for group C, and 2.09 for group D. Mean postchemotherapy SUVt for group B was 4.74. Thymic rebound (mean SUVt, 2.89) was seen in 44% of patients at a mean interval of 10 months from the end of chemotherapy. The differences between prechemotherapy SUVt of mediastinal lymphoma and normal thymus and postchemotherapy SUVt of lymphoma recurrence and thymic rebound were highly significant (P<.001). CONCLUSION: SUVt is a sensitive predictor for differentiation of normal thymus or thymic rebound from mediastinal lymphoma. SUVt of 3.4 or higher is a strong predictor of mediastinal lymphoma.

Thyroid and hepatic function after high-dose 131 I-metaiodobenzylguanidine (131 I-MIBG) therapy for neuroblastoma.

BACKGROUND: (131) I-Metaiodobenzylguanidine ((131) I-MIBG) provides targeted radiotherapy for children with neuroblastoma, a malignancy of the sympathetic nervous system. Dissociated radioactive iodide may concentrate in the thyroid, and (131) I-MIBG is concentrated in the liver after (131) I-MIBG therapy. The aim of our study was to analyze the effects of (131) I-MIBG therapy on thyroid and liver function. PROCEDURE: Pre- and post-therapy thyroid and liver functions were reviewed in a total of 194 neuroblastoma patients treated with (131) I-MIBG therapy. The cumulative incidence over time was estimated for both thyroid and liver toxicities. The relationship to cumulative dose/kg, number of treatments, time from treatment to follow-up, sex, and patient age was examined. RESULTS: In patients who presented with Grade 0 or 1 thyroid toxicity at baseline, 12 ± 4% experienced onset of or worsening to Grade 2 hypothyroidism and one patient developed Grade 2 hyperthyroidism by 2 years after (131) I-MIBG therapy. At 2 years post-(131) I-MIBG therapy, 76 ± 4% patients experienced onset or worsening of hepatic toxicity to any grade, and 23 ± 5% experienced onset of or worsening to Grade 3 or 4 liver toxicity. Liver toxicity was usually transient asymptomatic transaminase elevation, frequently confounded by disease progression and other therapies. CONCLUSION: The prophylactic regimen of potassium iodide and potassium perchlorate with (131) I-MIBG therapy resulted in a low rate of significant hypothyroidism. Liver abnormalities following (131) I-MIBG therapy were primarily reversible and did not result in late toxicity. (131) I-MIBG therapy is a promising treatment for children with relapsed neuroblastoma with a relatively low rate of symptomatic thyroid or hepatic dysfunction.

124I-MIBG PET/CT to Monitor Metastatic Disease in Children with Relapsed Neuroblastoma.

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

Radiation dose estimation using preclinical imaging with 124I-metaiodobenzylguanidine (MIBG) PET.

PURPOSE: A pretherapy 124I-metaiodobenzylguanidine (MIBG) positron emission tomography (PET)/computed tomography (CT) provides a potential method to estimate radiation dose to normal organs, as well as tumors prior to 131I-MIBG treatment of neuroblastoma or pheochromocytoma. The aim of this work was to estimate human-equivalent internal radiation dose of 124I-MIBG using PET/CT data in a murine xenograft model. METHODS: Athymic mice subcutaneously implanted with NB1691 cells that express high levels of human norepinephrine transporter (n = 4) were imaged using small animal microPET/CT over 96 h (approximate imaging time points: 0.5, 2, 24, 52, and 96 h) after intravenous administration of 3.07-4.84 MBq of 124I-MIBG via tail vein. The tumors did not accumulate 124I-MIBG to a detectable level. All four animals were considered as control and organ radiation dosimetry was performed. Volumes of interest were drawn on the coregistered CT images for thyroid, heart, lung, liver, kidney, and bladder, and transferred to PET images to obtain pharmacokinetic data. Based on tabulated organ mass distributions for both mice and adult male human, preclinical pharmacokinetic data were extrapolated to their human-equivalent values. Radiation dose estimations for different age groups were performed using the OLINDA/EXM software with modified tissue weighting factors in the recent International Commission on Radiological Protection (ICRP) Publication 103. RESULTS: The mean effective dose from 124I-MIBG using weighting factors from ICRP 103 to the adult male was estimated at 0.25 mSv/MBq. In different age groups, effective doses using values from ICRP 103 were estimated as follows: Adult female: 0.34, 15-yr-old: 0.39 mSv/MBq, 10-yr-old: 0.58 mSv/MBq, 5-yr-old: 1.03 mSv/MBq, 1-yr-old: 1.92 mSv/MBq, and newborn: 3.75 mSv/ MBq. For comparison, the reported effective dose equivalent of 124I-NaI for adult male (25% thyroid uptake, MIRD Dose Estimate Report No. 5) was 6.5 mSv/MBq. CONCLUSIONS: The authors estimated human-equivalent internal radiation dose of 124I-MIBG using preclinical imaging data. As a reference, the effective dose estimation showed that 124I-MIBG would deliver less radiation dose than 124I-NaI, a radiotracer already being used in patients with thyroid cancer.

Diagnostic value of PET/CT for the staging and restaging of pediatric tumors.

OBJECTIVE: The objective of this retrospective study was to compare the diagnostic value of 2-[(18)F]fluoro-2-deoxy-D: -glucose positron emission tomography ((18)F-FDG PET)/CT versus (18)F-FDG PET and CT alone for staging and restaging of pediatric solid tumors. METHODS: Forty-three children and adolescents (19 females and 24 males; mean age, 15.2 years; age range, 6-20 years) with osteosarcoma (n = 1), squamous cell carcinoma (n = 1), synovial sarcoma (n = 2), germ cell tumor (n = 2), neuroblastoma (n = 2), desmoid tumor (n = 2), melanoma (n = 3), rhabdomyosarcoma (n = 5), Hodgkin's lymphoma (n = 7), non-Hodgkin-lymphoma (n = 9), and Ewing's sarcoma (n = 9) who had undergone (18)F-FDG PET/CT imaging for primary staging or follow-up of metastases were included in this study. The presence, location, and size of primary tumors was determined separately for PET/CT, PET, and CT by two experienced reviewers. The diagnosis of the primary tumor was confirmed by histopathology. The presence or absence of metastases was confirmed by histopathology (n = 62) or clinical and imaging follow-up (n = 238). RESULTS: The sensitivities for the detection of solid primary tumors using integrated (18)F-FDG PET/CT (95%), (18)F-FDG PET alone (73%), and CT alone (93%) were not significantly different (p > 0.05). Seventeen patients showed a total of 153 distant metastases. Integrated PET/CT had a significantly higher sensitivity for the detection of these metastases (91%) than PET alone (37%; p < 0.05), but not CT alone (83%; p > 0.05). When lesions with a diameter of less than 0.5 cm were excluded, PET/CT (89%) showed a significantly higher specificity compared to PET (45%; p < 0.05) and CT (55%; p < 0.05). In a sub-analysis of pulmonary metastases, the values for sensitivity and specificity were 90%, 14%, 82% and 63%, 78%, 65%, respectively, for integrated PET/CT, stand-alone PET, and stand-alone CT. For the detection of regional lymph node metastases, (18)F-FDG PET/CT, (18)F-FDG PET alone, and CT alone were diagnostically correct in 83%, 61%, and 42%. A sub-analysis focusing on the ability of PET/CT, PET, and CT to detect osseous metastases showed no statistically significant difference between the three imaging modalities (p > 0.05). CONCLUSION: Our study showed a significantly increased sensitivity of PET/CT over that of PET for the detection of distant metastases but not over that of CT alone. However, the specificity of PET/CT for the characterization of pulmonary metastases with a diameter > 0.5 cm and lymph node metastases with a diameter of <1 cm was significantly increased over that of CT alone.

Technical Note: Simplified and practical pretherapy tumor dosimetry - A feasibility study for 131 I-MIBG therapy of neuroblastoma using 124 I-MIBG PET/CT.

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.

Role of IV iodinated contrast material in 18F-FDG PET/CT of liver metastases.

OBJECTIVE: The purpose of our study was to investigate the role of IV iodinated contrast material in the evaluation of hepatic metastases at (18)F-FDG PET/CT. MATERIALS AND METHODS: We retrospectively identified 39 patients (25 men and 14 women) with suspected isolated hepatic metastases from colorectal cancer who underwent FDG PET/CT. The CT protocol included acquisition of unenhanced and multiphase contrast-enhanced CT images through the liver. At two separate sittings, four readers (two radiologists and two nuclear medicine physicians) noted and characterized all hepatic lesions in consensus, first based on PET and unenhanced CT images and later based on PET and contrast-enhanced CT images. The nature of detected lesions was established by histopathologic or clinicoradiologic correlation. RESULTS: A total of 178 hepatic lesions were identified, consisting of 137 metastases and 41 benign lesions. Using lesion-based analyses with Obuchowski's method for paired observations, 172 of 178 lesions (97%) were detected at PET/contrast-enhanced CT compared with only 135 of 178 (76%) at PET/unenhanced CT (p = 0.0004). Specifically, 114 of 137 (83%) hepatic metastases were detected on PET/contrast-enhanced CT compared with 92 of 137 (67%) on PET/unenhanced CT (p = 0.012). One hundred thirty-one of 178 lesions (73%) were accurately characterized at PET/contrast-enhanced CT compared with 101 of 178 (57%) at PET/unenhanced CT (p = 0.004). CONCLUSION: IV iodinated contrast material administration improves the detection of hepatic metastases and the characterization of focal hepatic lesions at PET/CT.

Quantitative and Visual Assessments toward Potential Sub-mSv or Ultrafast FDG PET Using High-Sensitivity TOF PET in PET/MRI.

PURPOSE: Newer high-performance time-of-flight (TOF) positron emission tomography (PET) systems have the capability to preserve diagnostic image quality with low count density, while maintaining a high raw photon detection sensitivity that would allow for a reduction in injected dose or rapid data acquisition. To assess this, we performed quantitative and visual assessments of the PET images acquired using a highly sensitive (23.3 cps/kBq) large field of view (25-cm axial) silicon photomultiplier (SiPM)-based TOF PET (400-ps timing resolution) integrated with 3 T-MRI in comparison to PET images acquired on non-TOF PET/x-ray computed tomography (CT) systems. PROCEDURES: Whole-body 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/CT was acquired for 15 patients followed by whole body PET/magnetic resonance imaging (MRI) with an average injected dose of 325 ± 84 MBq. The PET list mode data from PET/MRI were reconstructed using full datasets (4 min/bed) and reduced datasets (2, 1, 0.5, and 0.25 min/bed). Qualitative assessment between PET/CT and PET/MR images were made. A Likert-type scale between 1 and 5, 1 for non-diagnostic, 3 equivalent to PET/CT, and 5 superior quality, was used. Maximum and mean standardized uptake values (SUVmax and SUVmean) of normal tissues and lesions detected were measured and compared. RESULTS: Mean visual assessment scores were 3.54 ± 0.32, 3.62 ± 0.38, and 3.69 ± 0.35 for the brain and 3.05 ± 0.49, 3.71 ± 0.45, and 4.14 ± 0.44 for the whole-body maximum intensity projections (MIPs) for 1, 2, and 4 min/bed PET/MR images, respectively. The SUVmean values for normal tissues were lower and statistically significant for images acquired at 4, 2, 1, 0.5, and 0.25 min/bed on the PET/MR, with values of - 18 ± 28 % (p < 0.001), - 16 ± 29 % (p = 0.001), - 16 ± 31 % (p = 0.002), - 14 ± 35 % (p < 0.001), and - 13 ± 34 % (p = 0.002), respectively. SUVmax and SUVpeak values of all lesions were higher and statistically significant (p < 0.05) for 4, 2, 1, 0.50, and 0.25 min/bed PET/MR datasets. CONCLUSION: High-sensitivity TOF PET showed comparable but still better visual image quality even at a much reduced activity in comparison to lower-sensitivity non-TOF PET. Our data translates to a seven times reduction in either injection dose for the same time or total scan time for the same injected dose. This "ultra-sensitivity" PET system provides a path to clinically acceptable extremely low-dose FDG PET studies (e.g., sub 1 mCi injection or sub-mSv effective dose) or PET studies as short as 1 min/bed (e.g., 6 min of total scan time) to cover whole body without compromising diagnostic performance.