18F-Fluciclovine Uptake in Thymoma Demonstrated on PET/MRI
A 68-year-old man with a history of prostate cancer post-primary treatment presented with rising prostate-specific antigen levels and was referred for F-fluciclovine PET/MRI to localize recurrent disease. PET/MRI revealed a solitary focus of uptake in a soft tissue nodule in the anterior mediastinum, which was resected and found to be a type B2 thymoma. F-fluciclovine uptake is mediated by amino acid transporters, primarily alanine-serine-cysteine transporter 2 and L-type amino acid transporter 1, previously demonstrated to be expressed on thymic carcinomas. This case highlights the possibility of overexpression of amino acid transporters in thymomas as well, rarely described before.
Diffusion MRI biomarkers of white matter microstructure vary nonmonotonically with increasing cerebral amyloid deposition
Beta amyloid (AÎ²) accumulation is the earliest pathological marker of Alzheimer's disease (AD), but early AD pathology also affects white matter (WM) integrity. We performed a cross-sectional study including 44 subjects (23 healthy controls and 21 mild cognitive impairment or early AD patients) who underwent simultaneous PET-MR using 18F-Florbetapir, and were categorized into 3 groups based on AÎ² burden: AÎ²-Â [mean mSUVr â‰¤1.00], AÎ²i [1.00 < mSUVr <1.17], AÎ²+ [mSUVr â‰¥1.17]. Intergroup comparisons of diffusion MRI metrics revealed significant differences across multiple WM tracts. AÎ²i group displayed more restricted diffusion (higher fractional anisotropy, radial kurtosis, axonal water fraction, and lower radial diffusivity) than both AÎ²- and AÎ²+ groups. This nonmonotonic trend was confirmed by significant continuous correlations between mSUVr and diffusion metrics going in opposite direction for 2 cohorts: pooled AÎ²-/AÎ²i and pooled AÎ²i/AÎ²+. The transient period of increased diffusion restriction may be due to inflammation that accompanies rising AÎ² burden. In the later stages of AÎ² accumulation, neurodegeneration is the predominant factor affecting diffusion.
Brain 18F-FDG-PET: Utility in the Diagnosis of Dementia and Epilepsy
BACKGROUND:The authors reviewed the two most common current uses of brain 18F-labeled fluoro-2-deoxyglucose positron emission tomography (FDG-PET) at a large academic medical center. For epilepsy patients considering surgical management, FDG-PET can help localize epileptogenic lesions, discriminate between multiple or discordant EEG or MRI findings, and predict prognosis for post-surgical seizure control. In elderly patients with cognitive impairment, FDG-PET often demonstrates lobar-specific patterns of hypometabolism that suggest particular underlying neurodegenerative pathologies, such as Alzheimer's disease. FDG-PET of the brain can be a key diagnostic modality and contribute to improved patient care.
Impact of MR-guided PET reconstruction on seizure foci localization with FDG PET [Meeting Abstract]
Aim: Determine if MR-guided FDG-PET reconstruction improves diagnostic accuracy and epileptogenic lesion localization for patients with focal epilepsy. Introduction: Abnormalities detected on MRI or FDG PET alter clinical management and prognosis in patients with focal epilepsy considering surgery (1). Concordant MRI findings are not always present, whereas -80% of adult patients with chronic seizures have FDG PET abnormalities. State-of-art FDG PET, however, remains limited by partial volume effects (PVEs) that reduce sensitivity particularly for extra-temporal epilepsy (2). MR-guided (MRG) PET reconstruction reduces PVEs (3). We tested the hypothesis that MRG PET reconstruction increases correct localization of epileptogenic lesions across readers with different levels of clinical experience.
Method(s): After IRB approval, a neuroradiologist with 1000+ brain PET interpretations identified 26 epilepsy subjects that underwent simultaneous FDG PET-MRI (Siemens Biograph mMR, Siemens Healthcare, Erlangen, Germany) with final adjudicated diagnosis either as normal (N=10) or cortical dysplasia (N=16). PET emission images were reconstructed using conventional OSEM and MRG PET reconstructions (asymmetric Bowsher prior with 3D MPRAGE as anatomical prior image). Then, 3 blinded readers (with 12, 6 & 18 years of experience; respectively) evaluated cases containing either OSEM or MRG PET in the sagittal, axial and coronal planes for each case (MRI data was not provided). Readers determined if there were focal FDG abnormalities consistent with an epileptogenic zone, then assigned ordinal values to image quality (0-3; where 3 was "excellent") and diagnostic confidence (1-3; where 3 = "definite" abnormality or normal study).
Result(s): The figure below shows coronal OSEM and MRG PET reconstructions (A & B respectively) with co-registered MRI (C) - MRG PET better demonstrated the focal FDG abnormality associated with right frontal cortical dysplasia. All 3 readers rated MRG PET images higher in overall quality (2.6 +/- 0.7 vs 2.0 +/- 0.5, Mann-Whitney test, P<0.00001). Reconstruction method did not affect diagnostic confidence (2.6 +/- 0.7 vs 2.9 +/- 0.4, Mann-Whitney test, P=0.555). Readers 2 & 3 (with less experience reading brain FDG PET), improved their localization of the seizure focus using MRG PET images from 42.9 to 75%, and 50 to 75% correct respectively. Reader 1, with the most experience, demonstrated no change in correct localization (85.7 vs 83.3%), but reported more confidence in the diagnosis (P=0.033). Global percentage correct for all 3 raters increased from 59.5% to 77.8% (chi-squared test, P=0.086). MRG PET images increased interpretation sensitivity from 69% to 75%, specificity from 70% to 83% and accuracy from 70% to 78%, but these changes did not reach statistical significance.
Conclusion(s): These initial results demonstrate that MRG PET reconstruction of FDG data can increase correct seizure localization for PET readers with less experience. Study limitations include that clinical history, anatomical correlation and non-attenuation corrected FDG PET images were not available to blinded readers. Future work will increase the number of subjects evaluated by the 3 readers to increase statistical power
Radiotherapy induces responses of lung cancer to CTLA-4 blockade
Focal radiation therapy enhances systemic responses to anti-CTLA-4 antibodies in preclinical studies and in some patients with melanoma1-3, but its efficacy in inducing systemic responses (abscopal responses) against tumors unresponsive to CTLA-4 blockade remained uncertain. Radiation therapy promotes the activation of anti-tumor T cells, an effect dependent on type I interferon induction in the irradiated tumor4-6. The latter is essential for achieving abscopal responses in murine cancers6. The mechanisms underlying abscopal responses in patients treated with radiation therapy and CTLA-4 blockade remain unclear. Here we report that radiation therapy and CTLA-4 blockade induced systemic anti-tumor T cells in chemo-refractory metastatic non-small-cell lung cancer (NSCLC), where anti-CTLA-4 antibodies had failed to demonstrate significant efficacy alone or in combination with chemotherapy7,8. Objective responses were observed in 18% of enrolled patients, and 31% had disease control. Increased serum interferon-Î² after radiation and early dynamic changes of blood T cell clones were the strongest response predictors, confirming preclinical mechanistic data. Functional analysis in one responding patient showed the rapid in vivo expansion of CD8 T cells recognizing a neoantigen encoded in a gene upregulated by radiation, supporting the hypothesis that one explanation for the abscopal response is radiation-induced exposure of immunogenic mutations to the immune system.
Comparison of hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging and positron emission tomography/computed tomography for evaluation of peripheral nerve sheath tumors in patients with neurofibromatosis type 1
Rapidly enlarging, painful plexiform neurofibromas (PN) in neurofibromatosis type 1 (NF1) patients are at higher risk for harboring a malignant peripheral nerve sheath tumor (MPNST). Fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has been used to support more invasive diagnostic and therapeutic interventions. However, PET/CT imparts an untoward radiation hazard to this population with tumor suppressor gene impairment. The use of FDG PET coupled with magnetic resonance imaging (MRI) rather than CT is a safer alternative but its relative diagnostic sensitivity requires verification. Ten patients (6 females, 4 males, mean age 27 years, range 8-54) with NF1 and progressive PN were accrued from our institutional NF Clinic. Indications for PET scanning included increasing pain and/or progressive disability associated with an enlarging PN on serial MRIs. Following a clinically indicated whole-body FDG PET/CT, a contemporaneous PET/MRI was obtained using residual FDG activity with an average time interval of 3-4 h FDG-avid lesions were assessed for both maximum standardized uptake value (SUVmax) from PET/CT and SUVmax from PET/MR and correlation was made between the two parameters. 26 FDG avid lesions were detected on both PET/CT and PET/MR with an accuracy of 100%. SUVmax values ranged from 1.4-10.8 for PET/CT and from 0.2-5.9 for PET/MRI. SUVmax values from both modalities demonstrated positive correlation (r = 0.45, P < 0.001). PET/MRI radiation dose was significantly lower (53.35% Â± 14.37% [P = 0.006]). In conclusion, PET/MRI is a feasible alternative to PET/CT in patients with NF1 when screening for the potential occurrence of MPNST. Reduction in radiation exposure approaches 50% compared to PET/CT.
Visual detection of regional brain hypometabolism in cognitively impaired patients is independent of positron emission tomography-magnetic resonance attenuation correction method
Fluorodeoxyglucose (FDG) positron emission tomography-magnetic resonance (PET/MR) is useful for the evaluation of cognitively-impaired patients. This study aims to assess two different attenuation correction (AC) methods (Dixon-MR and atlas-based) versus index-standard computed tomography (CT) AC for the visual interpretation of regional hypometabolism in patients with cognitive impairment. Two board-certified nuclear medicine physicians blindly scored brain region FDG hypometabolism as normal versus hypometabolic using two-dimensional (2D) and 3D FDG PET/MR images generated by MIM software. Regions were quantitatively assessed as normal versus mildly, moderately, or severely hypometabolic. Hypometabolism scores obtained using the different methods of AC were compared, and interreader, as well as intra-reader agreement, was assessed. Regional hypometabolism versus normal metabolism was correctly classified in 16 patients on atlas-based and Dixon-based AC map PET reconstructions (vs. CT reference AC) for 94% (90%-96% confidence interval [CI]) and 93% (89%-96% CI) of scored regions, respectively. The averaged sensitivity/specificity for detection of any regional hypometabolism was 95%/94% (P = 0.669) and 90%/91% (P = 0.937) for atlas-based and Dixon-based AC maps. Interreader agreement for detection of regional hypometabolism was high, with similar outcome assessments when using atlas- and Dixon-corrected PET data in 93% (Îš =0.82) and 93% (Îš =0.84) of regions, respectively. Intrareader agreement for detection of regional hypometabolism was high, with concordant outcome assessments when using atlas- and Dixon-corrected data in 93%/92% (Îš =0.79) and 92/93% (Îš =0.78). Despite the quantitative advantages of atlas-based AC in brain PET/MR, routine clinical Dixon AC yields comparable visual ratings of regional hypometabolism in the evaluation of cognitively impaired patients undergoing brain PET/MR and is similar in performance to CT-based AC. Therefore, Dixon AC is acceptable for the routine clinical evaluation of dementia syndromes.
Multi-parametric FDG PET/MRI as an early predictor of response to neoadjuvant chemotherapy in patients wit epithelial ovarian cancer [Meeting Abstract]
Purpose: There is limited data regarding how many cycles of chemotherapy are optimal prior to debulking surgery in metastatic ovarian cancer. Furthermore, early identification of non-responders would prompt discontinuation of chemotherapy and earlier surgical management. The purpose of our study was to investigate the performance of FDG PET, dynamic contrast-enhanced (DCE) and intra-voxel incoherent motion (IVIM) MR as early predictors of treatment response in ovarian cancer. Parametric images of molecular diffusion restriction (D), tissue perfusion (D[asterisk]), vascular volume fraction (F), blood->interstitium constant of transfer (Ktrans), interstitum->plasma constant of transfer (Kep), extravascular/extracellular volume % (Ve) and plasma volume % (Ve) were investigated along with routine measures of SUV and ADC. Materials & Methods: Five subjects with a new diagnosis of epithelial ovarian cancer enrolled in the study. All subjects underwent 3 cycles of standardized chemotherapy followed by cytoreduction (debulking surgery). FDG PET/MR including DCE and IVIM was performed at baseline (T1), after cycle 1 (T2) and after cycle 3 (T3) of chemotherapy. Final responses were categorized at T3 by RECIST 1.1. Olea 3.0 software was used to generate parametric images from the multi-B-value DWI and DCE-MR datasets at all three timepoints. Parametric DICOM images were then coregistered to anatomical datasets using MIMvista and fusion was manually adjusted to optimize co-registration of tumor lesions across the multiple datasets. VOIs were manually drawn on clearly visible solid tumor deposits on PET, DCE-MR and DWI MR images. The parametric images derived from IVIM and DCE-MR at T2 were analyzed as early predictors of final response. Results: Five subjects completed FDG PET and IVIM-MR, three of which underwent DCE-MR. All subjects were partial responders by RECIST at T3. SUV values were only available for 4/5 patients due to technical difficulties and DCE-MR was only available for 3/5. All 5 subjects had good IVIM data. At T2, the SUVmax decreased on average by -39% across all subjects (p<0.001) and the SUVmean decreased on average by -43% across all subjects (p<0.001). At T2, the ADCmean increased on average by +25% across all subjects (p<0.05). At T2, the molecular diffusion restriction (D) increased on average by +43% across all subjects, approaching statistical significance (p=0.058). Furthermore, D[asterisk], F, Kep, Ktrans, and Vp increased in some subjects and decreased in others, without any recognizable pattern. Ve decreased in 3/3 patients, however, not reaching statistical significance. Conclusions: In this current FDG PET/MR study of ovarian cancer, SUVmax and ADCmean values obtained after one cycle of chemotherapy were consistently associated with partial anatomical treatment responses at end of therapy. These findings are in agreement with pre-existing literature studying the value of SUV and ADC in early treatment response assessment. Only one of seven advanced perfusion/diffusion metrics (D; molecular diffusion restriction) was reliably associated with treatment response. This finding that D is associated with treatment response is not surprising given that it is based on ADC without the contribution of intravascular diffusion. Our current small dataset does not yet demonstrate the value of the remaining analyzed advanced DCE-MR and DWI parameters. Further study is required to determine the utility of DCE- and IVIM-derived parameters in early response assessment. Voxelwise correlative studies and other advanced data processing methods are underway to determine if these advanced quantitative parameters may provide further information in the early assessment of chemotherapy treatment response. (Table Presented)
A phase I trial of ganetespib in combination with paclitaxel and trastuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer
BACKGROUND: Targeted therapies in HER2-positive metastatic breast cancer significantly improve outcomes but efficacy is limited by therapeutic resistance. HER2 is an acutely sensitive Heat Shock Protein 90 (HSP90) client and HSP90 inhibition can overcome trastuzumab resistance. Preclinical data suggest that HSP90 inhibition is synergistic with taxanes with the potential for significant clinical activity. We therefore tested ganetespib, a HSP90 inhibitor, in combination with paclitaxel and trastuzumab in patients with trastuzumab-refractory HER2-positive metastatic breast cancer. METHODS: In this phase I dose-escalation study, patients with trastuzumab-resistant HER2-positive metastatic breast cancer received weekly trastuzumab (2 mg/kg) and paclitaxel (80 mg/m2) on days 1, 8, 15, and 22 of a 28-day cycle with escalating doses of ganetespib (100 mg/m2, 150 mg/m2, and a third cohort of 125 mg/m2 if needed) on days 1, 8, and 15. Therapy was continued until disease progression or toxicity. The primary objective was to establish the safety and maximum tolerated dose and/or recommended phase II dose (RP2D) of this therapy. The secondary objectives included evaluation of the effects of ganetespib on the pharmacokinetics of paclitaxel, and to make a preliminary assessment of the efficacy of the combination therapy. RESULTS: Dose escalation was completed for the two main cohorts without any observed dose-limiting toxicities. Nine patients received treatment. The median prior lines of anti-HER2 therapy numbered three (range 2-4), including prior pertuzumab in 9/9 patients and ado-trastuzumab emtansine (T-DM1) in 8/9 patients. The most common grade 1/2 adverse events (AEs) were diarrhea, fatigue, anemia, and rash. There were no grade 4 AEs related to ganetespib. The overall response rate was 22% (2/9 patients had partial response) and stable disease was seen in 56% (5/9 patients). The clinical benefit rate was 44% (4/9 patients). The median progression-free survival was 20 weeks (range 8-55). CONCLUSION: The RP2D of ganetespib is 150 mg/m2 in combination with weekly paclitaxel plus trastuzumab. The combination was safe and well tolerated. Despite prior taxanes, pertuzumab, and T-DM1, clinical activity of this triplet regimen in this heavily pretreated cohort is promising and warrants further study in HER2-positive metastatic breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT02060253 . Registered 30 January 2014.
Ganglion Cyst on 131I Whole-Body Scintigraphy
Interpretation of iodine I whole-body scintigraphy can be challenging, as there are many nonpathologic findings that may present with increased radiotracer uptake. Radiotracer uptake has been reported in the literature involving the salivary glands, thymus, renal cysts, skin contamination, and other benign etiologies. We present the case of an incidental right wrist ganglion cyst demonstrating persistent increased uptake on I whole-body scintigraphy.