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18F-FDOPA PET/MRI for monitoring early response to bevacizumab in children with recurrent brain tumors.

ABSTRACT: Background:Noninvasively predicting early response to therapy in recurrent pediatric brain tumors provides a challenge. 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-FDOPA) PET/MRI has not been previously studied as a tool to evaluate early response to antiangiogenic therapy in children. The purpose of this study was to evaluate the safety and feasibility of using 18F-FDOPA PET/MRI to assess response to bevacizumab in children with relapsed brain tumors. Materials and Methods:Six patients with recurrent gliomas (5 low-grade, 1 high-grade) planned to undergo treatment with bevacizumab were enrolled. 18F-FDOPA PET/MRI scans were obtained prior to and 4 weeks following the start of treatment, and these were compared with the clinical response determined at the 3-month MRI. The primary PET measure was metabolic tumor volume (MTV) at 10 to 15 min after 18F-FDOPA injection. For each tumor, the MTV was determined by manually defining initial tumor volumes of interest (VOI) and then applying a 1.5-fold threshold relative to the mean standardized uptake value (SUV) of a VOI in the frontal lobe contralateral to the tumor. Results:18F-FDOPA PET/MRI was well tolerated by all patients. All tumors were well visualized with 18F-FDOPA on the initial study, with peak tumor uptake occurring approximately 10 min after injection. Maximum and mean SUVs as well as tumor-to-brain ratios were not predictors of response at 3 months. Changes in MTVs after therapy ranged from 23% to 98% (n = 5). There is a trend towards the percent MTV change seen on the 4-week scan correlating with progression-free survival. Conclusion:18F-FDOPA PET/MRI was well tolerated in pediatric patients and merits further investigation as an early predictor of response to therapy.

SUBMITTER: Gauvain K

PROVIDER: S-EPMC5909807 | biostudies-other | 2018 Mar

REPOSITORIES: biostudies-other

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<sup>18</sup>F-FDOPA PET/MRI for monitoring early response to bevacizumab in children with recurrent brain tumors.

Gauvain Karen K Ponisio Maria Rosana MR Barone Amy A Grimaldi Michael M Parent Ephraim E Leeds Hayden H Goyal Manu M Rubin Joshua J McConathy Jonathan J

Neuro-oncology practice 20170525 1

<h4>Background</h4>Noninvasively predicting early response to therapy in recurrent pediatric brain tumors provides a challenge. 3,4-dihydroxy-6-[<sup>18</sup>F]fluoro-L-phenylalanine (<sup>18</sup>F-FDOPA) PET/MRI has not been previously studied as a tool to evaluate early response to antiangiogenic therapy in children. The purpose of this study was to evaluate the safety and feasibility of using <sup>18</sup>F-FDOPA PET/MRI to assess response to bevacizumab in children with relapsed brain tumor ...[more]

PMID: 29692922

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Project description:BACKGROUND:To propose a personalized therapeutic approach in osteosarcoma treatment, we assessed whether sequential [18F]FDG PET/CT (PET/CT) could predict the outcome of patients with osteosarcoma of the extremities after one cycle and two cycles of neoadjuvant chemotherapy. METHODS:A total of 73 patients with AJCC stage II extremity osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy were retrospectively analyzed in this study. All patients underwent PET/CT before (PET0), after 1 cycle (PET1), and after the completion of neoadjuvant chemotherapy (PET2), respectively. Maximum standardized uptake value (SUVmax) (corrected for body weight) and the % changes of SUVmax were calculated, and histological responses were evaluated after surgery. Receiver-operating characteristic (ROC) curve analyses and the Cox proportional hazards models were used to analyze whether imaging and clinicopathologic parameters could predict event-free survival (EFS). RESULTS:A total of 36 patients (49.3%) exhibited a poor histologic response and 17 patients (23.3%) showed events (metastasis in 15 and local recurrence in 2). SUVmax on PET2 (SUV2), the percentage change of SUVmax between PET0 and PET1 (?%SUV01), and between PET0 and PET2 (?%SUV02) most accurately predicted events using the ROC curve analysis. SUV2 (relative risk, 8.86; 95% CI, 2.25-34.93), ?%SUV01 (relative risk, 5.97; 95% CI, 1.47-24.25), and ?%SUV02 (relative risk, 6.00; 95% CI, 1.16-30.91) were independent predicting factors for EFS with multivariate analysis. Patients with SUV2 over 5.9 or ?%SUV01 over -?39.8% or ?%SUV02 over -?54.1% showed worse EFS rates than others (p < 0.05). CONCLUSIONS:PET evaluation after 1 cycle of presurgical chemotherapy can predict the clinical outcome of extremity osteosarcoma. [18F]FDG PET, which shows a potential role in the early evaluation of the modification of timing of local control, can be a useful modality for early response monitoring of neoadjuvant chemotherapy.

Project description:Background and purposeThe interpretation of the radiologic response of bevacizumab-treated patients with recurrent high-grade gliomas represents a unique challenge. Delayed-contrast MR imaging was recently introduced for calculating treatment-response-assessment maps in patients with brain tumors, providing clear separation between active tumor and treatment effects. We studied the application of standard and delayed-contrast MR imaging for assessing and predicting the response to bevacizumab.Materials and methodsTwenty-four patients with recurrent high-grade gliomas were scanned before and during bevacizumab treatment by standard and delayed-contrast MR imaging. The mean change in lesion volumes of responders (overall survival, ≥1 year) and nonresponders (overall survival, <1 year) was studied. The lesion volumes at baseline and the changes in lesion volumes 1 month after treatment initiation, calculated from standard and delayed-contrast MRIs, were studied as possible predictors of outcome. In scans acquired at progression, the average change in lesion volume from previous follow-up in standard and delayed-contrast MRIs was compared.ResultsResponse and progression patterns were identified from the mean change in lesion volumes, depicted from conventional T1WI, delayed contrast-enhanced MR imaging, and DSC MR imaging. Thresholds for early prediction of response were calculated by using these sequences. For each predictor, sensitivity, specificity, positive predictive values, and negative predictive values were calculated, reaching 85.7%, 87.5%, 75%, and 93.3% for conventional T1WI; 100%, 87.5%, 77.8%, and 100% for delayed-contrast MR imaging; and 75%, 78.6%, 50%, and 91.7% for DSC MR imaging. The benefit of delayed-contrast MR imaging in separating responders and nonresponders was further confirmed by using log-rank tests (conventional T1WI, P = .0022; delayed-contrast MR imaging, P < .0001; DSC MR imaging, P = .0232) and receiver operating characteristic analyses. At progression, the increase in lesion volumes in delayed-contrast MR imaging was 37.5% higher than the increase in conventional T1WI (P < .01); these findings suggest that progression may be depicted more effectively in treatment-response-assessment maps.ConclusionsThe benefit of contrast-enhanced MR imaging for assessing and predicting the response to bevacizumab was demonstrated. The increased sensitivity of the treatment-response-assessment maps reflects their potential contribution to the management of bevacizumab-treated patients with recurrent high-grade glioma.

Project description:UnlabelledWe assessed the value of fusion (18)F-fluoromethylcholine ((18)F-choline) PET/MRI for image-guided (targeted) prostate biopsies to detect significant prostate cancer (Gleason ≥ 3 + 4) compared with standard (systematic 12-core) biopsies.MethodsWithin an ongoing prospective clinical trial, hybrid (18)F-choline PET/CT and multiparametric 3T MRI (mpMRI) of the pelvis were performed in 36 subjects with a rising prostate-specific antigen for known (n = 15) or suspected (n = 21) prostate cancer before a prostate biopsy procedure. PET and T2-weighted MR volumes of the prostate were spatially registered using commercially available software. Biopsy targets were selected on the basis of visual appearance on MRI and graded as low, intermediate, or high risk for significant disease. Volumes of interest were defined for MR-identified lesions. (18)F-choline uptake measures were obtained from the MR target and a mirrored background volume of interest. The biopsy procedure was performed after registration of real-time transrectal ultrasound with T2-weighted MR and included image-guided cores plus standard cores. Histologic results were determined from standard and targeted biopsy cores as well as prostatectomy specimens (n = 10).ResultsFifteen subjects were ultimately identified with Gleason ≥ 3 + 4 prostate cancer, of which targeted biopsy identified significantly more (n = 12) than standard biopsies (n = 5; P = 0.002). A total of 52 lesions were identified by mpMRI (19 low, 18 intermediate, 15 high risk), and mpMRI-assigned risk was a strong predictor of final pathology (area under the curve = 0.81; P < 0.001). When the mean (18)F-choline target-to-background ratio was used, the addition of (18)F-choline to mpMRI significantly improved the prediction of Gleason ≥ 3 + 4 cancers over mpMRI alone (area under the curve = 0.92; P < 0.001).ConclusionFusion PET/MRI transrectal ultrasound image registration for targeted prostate biopsies is clinically feasible and accurate. The addition of (18)F-choline PET to mpMRI improves the identification of significant prostate cancer.

Project description:BackgroundThere is an increasing need to characterize biological processes for early prediction and monitoring of response to endocrine therapy in breast cancer using multiple positron emission tomography (PET) imaging probes. However, use of more than two PET tracers in a single clinical trial is quite challenging. In this study we carried out a longitudinal investigation of 18F-FES, 18F-FDG, and 18F-FMISO PET imaging probes for early prediction and monitoring of response to endocrine therapy in a mouse xenograft model of estrogen receptor (ER)-positive breast cancer.MethodER+ human breast cancer ZR-75-1 models were established in female mice that were then randomly assigned to a treatment (fulvestrant, 5.0 mg/week for 21 days) or vehicle group. Micro-PET/CT imaging with 18F-FES, 18F-FDG, and 18F-FMISO was performed on days 0, 3, 14, and 21 after treatment. The uptake value (percentage injected dose per gram, %ID/g) for each probe in tumor (T) tissue and contralateral muscle (M) was measured for quantitative analysis and T/M calculation. Tumor volume was measured to record tumor growth at each time point. Tumor tissues were sampled for immunohistochemical staining of ER expression. Correlations for tumor volume and ERα levels with uptake data for the probe were tested.ResultsUptake data for 18F-FES in ZR-75-1 tumor tissues corresponded well with tumor response to endocrine therapy, but not for 18F-FDG and 18F-FMISO, according to longitudinal micro-PET/CT imaging and quantitative correlation analysis. There was a significant positive correlation between 18F-FES uptake and ER levels (%ID/gmax r2 = 0.76, P< 0.05; T/M r2 = 0.82, P<0.05). Notably, 18F-FES uptake on day 3 was significantly correlated with the day 21/baseline tumor volume ratio (%ID/gmax r2 = 0.74, P < 0.05; T/M r2 = 0.78, P < 0.05).ConclusionsComparison of 18F-FES, 18F-FDG, and 18F-FMISO probes revealed that 18F-FES PET/CT molecular imaging can provide a precise early prediction of tumor response to endocrine therapy in ER+ breast cancer in a ZR-75-1 xenograft model. This molecular imaging strategy with 18F-FES PET/CT will be useful in evaluating the efficacy of endocrine therapies and in developing new endocrine drugs.

Dataset Information

18F-FDOPA PET/MRI for monitoring early response to bevacizumab in children with recurrent brain tumors.

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<sup>18</sup>F-FDOPA PET/MRI for monitoring early response to bevacizumab in children with recurrent brain tumors.

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