Dataset Information

Imaging acquisition technique influences interpretation of positron emission tomography vascular activity in large-vessel vasculitis.

ABSTRACT:

Objectives

To determine the impact of imaging acquisition time on interpretation of disease activity on ¹⁸F-fluorodeoxyglucose positron emission tomography (PET) in large-vessel vasculitis (LVV) and assess the relationship between clinical features and image acquisition time.

Methods

Patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK) were recruited into a prospective, observational cohort. After a single injection of FDG, all patients underwent two sequential PET scans at one and two-hour time points. Images were interpreted for active vasculitis by subjective assessment, qualitative assessment, and semi-quantitative assessment. Agreement was assessed by percent agreement, Cohen's kappa, and McNemar's test. Multivariable logistic regression identified associations between PET activity and clinical variables.

Results

79 patients (GCA = 44, TAK = 35) contributed 168 paired one and two-hour PET studies. A total of 94 out of 168 scans (56%) were interpreted as active at the one-hour time point, and 129 scans (77%) were interpreted as active at the two-hour time point (p < 0.01). Associations between clinical variables and PET activity categories (dual inactive, delayed active, dual active) were evaluated. Using multivariable nominal regression, clinically active disease was significantly more common in patients in the delayed active group (Odds Ratio 1.94, 95%CI 1.13-3.53; p? = ?0.02) and the dual active group (Odds Ratio 1.71, 95%CI 1.06-2.93; p? = ?0.04) compared to the dual inactive group.

Conclusions

Imaging protocol significantly influences interpretation of PET activity in LVV. A substantial proportion of patients with LVV have PET activity only detected by delayed imaging. These patients were significantly more likely to have concomitant clinically-determined active disease.

SUBMITTER: Quinn KA

PROVIDER: S-EPMC6981042 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Imaging acquisition technique influences interpretation of positron emission tomography vascular activity in large-vessel vasculitis.

Quinn Kaitlin A KA Rosenblum Joel S JS Rimland Casey A CA Gribbons K Bates KB Ahlman Mark A MA Grayson Peter C PC

Seminars in arthritis and rheumatism 20190724 1

<h4>Objectives</h4>To determine the impact of imaging acquisition time on interpretation of disease activity on <sup>18</sup>F-fluorodeoxyglucose positron emission tomography (PET) in large-vessel vasculitis (LVV) and assess the relationship between clinical features and image acquisition time.<h4>Methods</h4>Patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK) were recruited into a prospective, observational cohort. After a single injection of FDG, all patients underwent two ...[more]

PMID: 31375256

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Project description:OBJECTIVE:To assess the clinical value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in a prospective cohort of patients with large vessel vasculitis (LVV) and comparator subjects. METHODS:Patients with Takayasu arteritis and giant cell arteritis were studied, along with a comparator group consisting of patients with hyperlipidemia, patients with diseases that mimic LVV, and healthy controls. Participants underwent clinical evaluation and FDG-PET imaging, and patients with LVV underwent serial imaging at 6-month intervals. We calculated sensitivity and specificity of FDG-PET interpretation for distinguishing patients with clinically active LVV from comparator subjects and from patients with disease in clinical remission. A qualitative summary score based on global arterial FDG uptake, the PET Vascular Activity Score (PETVAS), was used to study associations between activity on PET scan and clinical characteristics and to predict relapse. RESULTS:A total of 170 FDG-PET scans were performed in 115 participants (56 patients with LVV and 59 comparator subjects). FDG-PET distinguished patients with clinically active LVV from comparator subjects with a sensitivity of 85% (95% confidence interval [95% CI] 69, 94) and a specificity of 83% (95% CI 71, 91). FDG-PET scans were interpreted as active vasculitis in most patients with LVV in clinical remission (41 of 71 [58%]). Clinical disease activity status, disease duration, body mass index, and glucocorticoid use were independently associated with activity on PET scan. Among patients who underwent PET during clinical remission, future clinical relapse was more common in patients with a high PETVAS than in those with a low PETVAS (55% versus 11%; P = 0.03) over a median follow-up period of 15 months. CONCLUSION:FDG-PET provides information about vascular inflammation that is complementary to, and distinct from, clinical assessment in LVV. FDG-PET scan activity during clinical remission was associated with future clinical relapse.

Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

Project description:Purpose: Evans Blue (EB) is an azo dye that binds quantitatively with serum albumin. With an albumin binding, NOTA conjugated truncated Evan's blue (NEB) dye derived PET tracer, we aimed to establish a strategy for evaluating vascular permeability in malignant tumors via non-invasive PET. Experimental design: Sixty-minute dynamic PET using [18F]FAl-NEB was performed in three xenograft tumor models including INS-1 rat insulinoma, UM-SCC-22B human head and neck carcinoma and U-87 MG human glioblastoma. Tumor vascular permeability was quantified by the difference of the slopes between tumor and blood time-activity curve (TACs, expressed as Ps ). The method was further substantiated by EB extraction and colorimetric assay and correlates with that calculated from dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). The changes in tumor vasculature at different time points were assessed with NEB PET in U-87 MG and UM-SCC-22B tumor models after treatment with bevacizumab or doxorubicin. Result: The Ps values calculated from tumor and blood TACs from multiple time-point static images are consistent with those from dynamic images. Moreover, the Ps showed a positive and significant correlation with extracted EB concentration and KPS-MRI generated from DCE-MRI, which further confirmed the soundness of this methodology. The antiangiogenic effect of bevacizumab could be revealed by NEB PET in U-87 MG tumors as early as 8 hrs after therapy, demonstrated by a substantial decrease of Ps. On the contrary, there was no significant change of Ps in bevacizumab treated UM-SCC-22B tumors, compared with control group. However, the significant changes of Ps were overestimated in doxorubicin treated UM-SCC-22B tumors. Conclusions: We successfully developed a relatively convenient and novel strategy to evaluate vascular permeability and blood volume using NEB PET. This method will be advantageous in evaluating vascular permeability, promoting drug delivery, and monitoring tumor response to therapeutics that affect tumor angiogenesis.

Dataset Information

Imaging acquisition technique influences interpretation of positron emission tomography vascular activity in large-vessel vasculitis.

Objectives

Methods

Results

Conclusions

Publications

Imaging acquisition technique influences interpretation of positron emission tomography vascular activity in large-vessel vasculitis.

Similar Datasets

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