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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:In this study, kinetic parameters of the cellular proliferation tracer (18)F-3'-deoxy-3'-fluoro-L-thymidine (FLT) and the amino acid probe 3,4-dihydroxy-6-(18)F-fluoro-L-phenylalanine (FDOPA) were measured before and early after the start of therapy, and were used to predict the overall survival (OS) of patients with recurrent malignant glioma using multiple linear regression (MLR) analysis.High-grade recurrent brain tumors in 21 patients (11 men and 10 women, age range 26 - 76 years) were investigated. Each patient had three dynamic PET studies with each probe: at baseline and after 2 and 6 weeks from the start of treatment. Treatment consisted of biweekly cycles of bevacizumab (an angiogenesis inhibitor) and irinotecan (a chemotherapeutic agent). For each study, about 3.5 mCi of FLT (or FDOPA) was administered intravenously and dynamic PET images were acquired for 1 h (or 35 min for FDOPA). A total of 126 PET scans were analyzed. A three-compartment, two-tissue model was applied to estimate tumor FLT and FDOPA kinetic rate constants using a metabolite- and partial volume-corrected input function. MLR analysis was used to model OS as a function of FLT and FDOPA kinetic parameters for each of the three studies as well as their relative changes between studies. An exhaustive search of MLR models using three or fewer predictor variables was performed to find the best models.Kinetic parameters from FLT were more predictive of OS than those from FDOPA. The three-predictor MLR model derived using information from both probes (adjusted R(2)?=?0.83) fitted the OS data better than that derived using information from FDOPA alone (adjusted R(2)?=?0.41), but was only marginally different from that derived using information from FLT alone (adjusted R(2)?=?0.82). Standardized uptake values (either from FLT alone, FDOPA alone, or both together) gave inferior predictive results (best adjusted R(2)?=?0.25).For recurrent malignant glioma treated with bevacizumab and irinotecan, FLT kinetic parameters obtained early after the start of treatment (absolute values and their associated changes) can provide sufficient information to predict OS with reasonable confidence using MLR. The slight increase in accuracy for predicting OS with a combination of FLT and FDOPA PET information may not warrant the additional acquisition of FDOPA PET for therapy monitoring in patients with recurrent glioma.

Project description:We 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.Within 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).Fifteen 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).Fusion 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.

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Dataset Information

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

Publications

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

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