Co-registered Positron Emission Tomography Images Research Articles

18F]Fludarabine-PET as a promising tool for differentiating CNS lymphoma and glioblastoma: Comparative analysis with [18F]FDG in human xenograft models

This paper investigated whether positron emission tomography (PET) imaging with [18F]fludarabine ([18F]FDB) can help to differentiate central nervous system lymphoma (CNSL) from glioblastoma (GBM), which is a crucial issue in the diagnosis and management of patients with these aggressive brain tumors. Multimodal analyses with [18F]fluorodeoxyglucose ([18F]FDG), magnetic resonance imaging (MRI) and histology have also been considered to address the specificity of [18F]FDB for CNSL.Methods: Nude rats were implanted with human MC116 lymphoma-cells (n = 9) or U87 glioma-cells (n = 4). Tumor growth was monitored by MRI, with T2-weighted sequence for anatomical features and T1-weighted with gadolinium (Gd) enhancement for blood brain barrier (BBB) permeability assessment. For PET investigation, [18F]FDB or [18F]FDG (~11 MBq) were injected via tail vein and dynamic PET images were acquired up to 90 min after radiotracer injection. Paired scans of the same rat with the two [18F]-labelled radiotracers were investigated. Initial volumes of interest were manually delineated on T2w images and set on co-registered PET images and tumor-to-background ratio (TBR) was calculated to semi-quantitatively assess the tracer accumulation in the tumor. A tile-based method for image analysis was developed in order to make comparative analysis between radiotracer uptake and values extracted from immunohistochemistry staining.Results: In the lymphoma model, PET time-activity curves (TACs) revealed a differential response of [18F]FDB between tumoral and healthy tissues with average TBR varying from 2.45 to 3.16 between 5 to 90 min post-injection. In contrast, [18F]FDG demonstrated similar uptake profiles for tumoral and normal regions with TBR varying from 0.84 to 1.06 between these two time points. In the glioblastoma (GBM) model, the average TBRs were from 2.14 to 1.01 for [18F]FDB and from 0.95 to 1.65 for [18F]FDG. Therefore, inter-model comparisons showed significantly divergent responses (p < 0.01) of [18F]FDB between lymphoma and GBM, while [18F]FDG demonstrated overlap (p = 0.04) between the groups. Tumor characterization with histology (based mainly on Hoechst and CD79), as well as with MRI was overall in better agreement with [18F]FDB-PET than [18F]FDG with regard to tumor selectivity.Conclusions: [18F]FDB-PET demonstrated considerably greater specificity for CNSL when compared to [18F]FDG. It also permitted a more precise definition of target volume compared to contrast-enhanced MRI. Therefore, the potential of [18F]FDB-PET to distinguish CNSL from GBM is quite evident and will be further investigated in humans.

High-resolution (18)F-FDG PET/CT for assessing disease activity in rheumatoid and psoriatic arthritis: findings of a prospective pilot study.

Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) commonly affect the small joints of the wrist and hand. We evaluated the performance of a new, high-resolution extremity positron emission tomography (PET)/CT scanner for characterizing and quantifying pathologies associated with the two arthritides in the wrist and hand joints. Patients with RA or PsA underwent fluorine-18 fludeoxyglucose ((18)F-FDG) PET/CT wrist and hand imaging, respectively, on the high-resolution scanner. Calibrated CT images and co-registered PET images were reconstructed. PET/CT was derived for the radiocarpal and pisiform-triquetral compartments, joints with erosive changes, sites of synovitis or tenosynovitis and the nail bed and were correlated with clinical and MRI findings. Significantly elevated (18)F-FDG uptake was measured for the radiocarpal and pisiform-triquetral compartments and at sites of bone erosion, synovitis, pannus and oedema, compared with unaffected joints (p < 0.05) in patients with RA, consistent with their clinical findings. In patients with PsA, significantly elevated (18)F-FDG uptake was measured for joints with synovitis compared with unaffected joints (p < 0.05), with patterns of (18)F-FDG uptake along the tendons, at the enthesis and in the nail bed, consistent with tenosynovitis, enthesitis and nail dystrophy, respectively. High-resolution (18)F-FDG PET/CT imaging of the wrist and hand is feasible in an RA or PsA patient cohort and is capable of providing quantifiable measures of disease activity (synovitis, enthesitis, oedema and bone destruction). High-resolution PET/CT imaging shows promise as a tool for understanding the pathogenesis of the arthritic process and for non-invasive, objective assessment of RA or PsA severity and therapy selection.

Positron Emission Tomography for Serial Imaging of the Contused Adult Rat Spinal Cord

We investigated whether small-animal positron emission tomography (PET) could be used in combination with computed tomography (CT) imaging techniques for longitudinal monitoring of the injured spinal cord. In adult female Sprague-Dawley rats (n = 6), the ninth thoracic (T9) spinal cord segment was exposed by laminectomy and subsequently contused using the Infinite Horizon impactor (Precision System and Instrumentation, Lexington, KY) at 225 kDyn. In control rats (n = 4), the T9 spinal cord was exposed by laminectomy but not contused. At 0.5 hours and 3, 7, and 21 days postinjury, 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG) was given intravenously followed 1 hour later by sequential PET and CT. Regions of interest (ROIs) at T9 (contused) and T6 (uninjured) spinal cord segments were manually defined on CT images and aided by fiduciary markers superimposed onto the coregistered PET images. Monte Carlo simulation revealed that about 33% of the activity in the ROIs was due to spillover from adjacent hot areas. A simulation-based partial-volume compensation (PVC) method was developed and used to correct for this spillover effect. With PET-CT, combined with PVC, we were able to serially measure standardized uptake values of the T9 and T6 spinal cord segments and reveal small, but significant, differences. This approach may become a tool to assess the efficacy of spinal cord repair strategies.

Quantification of Local Tumor Response to Fractionated Radiation Therapy for Non-Hodgkin Lymphoma Using Weekly 18F-FDG PET/CT Imaging

To quantify, in a feasibility study, metabolic and volumetric response to fractionated radiation therapy (RT) using weekly (18)F fluoro-deoxyglucose positron emission tomography (PET) imaging for 10 non-Hodgkin lymphoma (NHL) patients, and to correlate them to clinical outcome. Ten patients with chemotherapy-refractory NHL planned for radical RT were prospectively entered into a research study. PET/computed tomography (CT) scans were acquired before RT, and repeated weekly during the 3- to 4-week course of RT, and at 1 and 3 months after therapy. Gross tumor volumes were contoured on CT scans and the corresponding maximum standardized uptake values (SUV(max)) determined in the coregistered PET images. The clinical outcomes of interest were local tumor response at 3 months post-RT and local tumor status at last follow-up or time of death. (18)F fluoro-deoxyglucose uptake from inflammation was rarely observed. The responses showed a large variability between patients. SUV(max) decreased consistently with a median of -2.1% per Gy (range, -3.3 to -0.7) and the median of the volumetric response was -2.2% per Gy (range, -2.8 to +0.5). Initial SUV(max) was not correlated with local control, whereas smaller initial tumor volume was, with smaller tumors more likely to achieve local control. The responses after treatment were also correlated to local control, but not the responses during treatment. Radiation does not confound the FDG uptake in the NHL tumor and normal tissues. Only smaller initial tumor volume and metabolic and volumetric response after completion of radiation therapy significantly correlated with eventual local control.

Magnetically Targeted Viral Envelopes: A PET Investigation of Initial Biodistribution

Gene and drug therapy for organ-specific diseases in part depends on the efficient delivery to a particular region of the body. We examined the biodistribution of a viral envelope commonly used as a nanoscale gene delivery vehicle using positron emission tomography (PET) and investigated the magnetic alteration of its biodistribution. Iron oxide nanoparticles and (18)F-fluoride were encapsulated by hemagglutinating virus of Japan envelopes (HVJ-Es). HVJ-Es were then injected intravenously in the rat and imaged dynamically using high-resolution PET. Control subjects received injections of encapsulated materials alone. For magnetic targeting, permanent magnets were fixed on the head during the scan. Based on the quantitative analysis of PET images, HVJ-Es accumulated in the liver and spleen and activity remained higher than control subjects for 2 h. Histological sections of the liver confirmed imaging findings. Pixel-wise activity patterns on coregistered PET images of the head showed a significantly different pattern for the subjects receiving magnetic targeting as compared to all control groups. Imaging demonstrated the initial biodistribution of a viral envelope within the rodent by providing quantitative behavior over time and in specific anatomical regions. Magnetic force altered the biodistribution of the viral envelope to a target structure, and could enable region-specific delivery of therapeutic vehicles noninvasively.

The Effect of Antiepileptic Drugs on 5‐HT1A–Receptor Binding Measured by Positron Emission Tomography

To study the effect of antiepileptic drugs (AEDs) on 5-HT(1A)-receptor binding in patients with temporal lobe epilepsy. 5-HT(1A)-receptor binding, measured by positron emission tomography, is reduced in patients with temporal lobe epilepsy. Antiepileptic drugs may act on the serotonergic system, as shown in animal models, and thus affect receptor-binding measurements. We analyzed the effect of AEDs on 5-HT(1A)-receptor binding in 31 patients and 10 normal controls. Patients with structural lesions, progressive neurologic disorders, or taking other medications were excluded. None had a seizure for >or=2 days before positron emission tomography (PET). [(18)F]FCWAY PET was performed on a GE Advance scanner with continuous EEG monitoring. Functional images of the distribution volume (V) were generated. Anatomic regions of interest were applied to co-registered PET images, after correction for partial-volume effect. Patients had significantly higher [(18)F]FCWAY free fraction (f(1)) than did controls. No AED effects were observed on interictal [(18)F]FCWAY binding after correction for plasma free fraction. [(18)F]FCWAY V/f1 reduction in epileptic foci was not affected by AEDs. 5-HT(1A)-receptor binding is reduced in temporal lobe epileptic foci after partial-volume correction. AED plasma free fractions should be measured when PET receptor studies are performed in patients with epilepsy.