Dataset Information

SPECT/CT Imaging of Mycobacterium tuberculosis Infection with [125I]anti-C3d mAb.

ABSTRACT: PURPOSE:Diagnosis and therapeutic monitoring of chronic bacterial infection requires methods to detect and localize sites of infection accurately. Complement C3 activation fragments are generated and covalently bound to selective bacterial pathogens during the immune response and can serve as biomarkers of ongoing bacterial infection. We have developed several probes for detecting tissue-bound C3 deposits, including a monoclonal antibody (mAb 3d29) that recognizes the tissue-bound terminal processing fragments iC3b and C3d but does not recognize native circulating C3 or tissue-bound C3b. PROCEDURES:To determine whether mAb 3d29 could be used to detect chronic Mycobacterium tuberculosis infection non-invasively, aerosol-infected female C3HeB/FeJ mice were injected with [125I]3d29 mAb and either imaged using single-photon emission computed tomography (SPECT)/X-ray computed tomography (CT) imaging at 24 and 48 h after radiotracer injection or being subjected to biodistribution analysis. RESULTS:Discrete lesions were detected by SPECT/CT imaging in the lungs and spleens of infected mice, consistent with the location of granulomas in the infected animals as detected by CT. Low-level signal was seen in the spleens of uninfected mice and no signal was seen in the lungs of healthy mice. Immunofluorescence microscopy revealed that 3d29 in the lungs of infected mice co-localized with aggregates of macrophages (detected with anti-CD68 antibodies). 3d29 was detected in the cytoplasm of macrophages, consistent with the location of internalized M. tuberculosis. 3d29 was also present within alveolar epithelial cells, indicating that it detected M. tuberculosis phagocytosed by other CD68-positive cells. Healthy controls showed very little retention of fluorescent or radiolabeled antibody across tissues. Radiolabeled 3d29 compared with radiolabeled isotype control showed a 3.5:1 ratio of increased uptake in infected lungs, indicating specific uptake by 3d29. CONCLUSION:3d29 can be used to detect and localize areas of infection with M. tuberculosis non-invasively by 24 h after radiotracer injection and with high contrast.

SUBMITTER: Foss CA

PROVIDER: S-EPMC6329677 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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SPECT/CT Imaging of Mycobacterium tuberculosis Infection with [<sup>125</sup>I]anti-C3d mAb.

Foss Catherine A CA Kulik Liudmila L Ordonez Alvaro A AA Jain Sanjay K SK Michael Holers V V Thurman Joshua M JM Pomper Martin G MG

Molecular imaging and biology 20190601 3

<h4>Purpose</h4>Diagnosis and therapeutic monitoring of chronic bacterial infection requires methods to detect and localize sites of infection accurately. Complement C3 activation fragments are generated and covalently bound to selective bacterial pathogens during the immune response and can serve as biomarkers of ongoing bacterial infection. We have developed several probes for detecting tissue-bound C3 deposits, including a monoclonal antibody (mAb 3d29) that recognizes the tissue-bound termin ...[more]

PMID: 29998399

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Project description:BackgroundThe introduction of hybrid SPECT/CT devices enables quantitative imaging in SPECT, providing a methodological setup for quantitation using SPECT tracers comparable to PET/CT. We evaluated a specific quantitative reconstruction algorithm for SPECT data using a 99mTc-filled NEMA phantom. Quantitative and qualitative image parameters were evaluated for different parametrizations of the acquisition and reconstruction protocol to identify an optimized quantitative protocol.ResultsThe reconstructed activity concentration (ACrec) and the signal-to-noise ratio (SNR) of all examined protocols (n = 16) were significantly affected by the parametrization of the weighting factor k used in scatter correction, the total number of iterations and the sphere volume (all, p < 0.0001). The two examined SPECT acquisition protocols (with 60 or 120 projections) had a minor impact on the ACrec and no significant impact on the SNR. In comparison to the known AC, the use of default scatter correction (k = 0.47) or object-specific scatter correction (k = 0.18) resulted in an underestimation of ACrec in the largest sphere volume (26.5 ml) by - 13.9 kBq/ml (- 16.3%) and - 7.1 kBq/ml (- 8.4%), respectively. An increase in total iterations leads to an increase in estimated AC and a decrease in SNR. The mean difference between ACrec and known AC decreased with an increasing number of total iterations (e.g., for 20 iterations (2 iterations/10 subsets) = - 14.6 kBq/ml (- 17.1%), 240 iterations (24i/10s) = - 8.0 kBq/ml (- 9.4%), p < 0.0001). In parallel, the mean SNR decreased significantly from 2i/10s to 24i/10s by 76% (p < 0.0001).ConclusionQuantitative SPECT imaging is feasible with the used reconstruction algorithm and hybrid SPECT/CT, and its consistent implementation in diagnostics may provide perspectives for quantification in routine clinical practice (e.g., assessment of bone metabolism). When combining quantitative analysis and diagnostic imaging, we recommend using two different reconstruction protocols with task-specific optimized setups (quantitative vs. qualitative reconstruction). Furthermore, individual scatter correction significantly improves both quantitative and qualitative results.

Project description:BackgroundLead-212 (212Pb) is a promising radionuclide for targeted therapy, as it decays to α-particle emitter bismuth-212 (212Bi) via β-particle emission. This extends the problematic short half-life of 212Bi. In preparation for upcoming clinical trials with 212Pb, the feasibility of quantitative single photon-emission computed tomography/computed tomography (SPECT/CT) imaging of 212Pb was studied, with the purpose to explore the possibility of individualised patient dosimetric estimation.ResultsBoth acquisition parameters (combining two different energy windows and two different collimators) and iterative reconstruction parameters (varying the iterations x subsets between 10 × 1, 15 × 1, 30 × 1, 30 × 2, 30 × 3, 30 × 4, and 30 × 30) were investigated to evaluate visual quality and quantitative uncertainties based on phantom images. Calibration factors were determined using a homogeneous phantom and were stable when the total activity imaged exceeded 1 MBq for all the imaging protocols studied, but they increased sharply as the activity decayed below 1 MBq. Both a 20% window centred on 239 keV and a 40% window on 79 keV, with dual scatter windows of 5% and 20%, respectively, could be used. Visual quality at the lowest activity concentrations was improved with the High Energy collimator and the 79 keV energy window. Fractional uncertainty in the activity quantitation, including uncertainties from calibration factors and small volume effects, in spheres of 2.6 ml in the NEMA phantom was 16-21% for all protocols with the 30 × 4 filtered reconstruction except the High Energy collimator with the 239 keV energy window. Quantitative analysis was possible both with and without filters, but the visual quality of the images improved with a filter.ConclusionsOnly minor differences were observed between the imaging protocols which were all determined suitable for quantitative imaging of 212Pb. As uncertainties generally decreased with increasing iterative updates in the reconstruction and recovery curves did not converge with few iterations, a high number of reconstruction updates are recommended for quantitative imaging.

Project description:BACKGROUND:It has been proposed, and preclinically demonstrated, that 161Tb is a better alternative to 177Lu for the treatment of small prostate cancer lesions due to its high emission of low-energy electrons. 161Tb also emits photons suitable for single-photon emission computed tomography (SPECT) imaging. This study aims to establish a SPECT protocol for 161Tb imaging in the clinic. MATERIALS AND METHODS:Optimal settings using various ?-camera collimators and energy windows were explored by imaging a Jaszczak phantom, including hollow-sphere inserts, filled with 161Tb. The collimators examined were extended low-energy general purpose (ELEGP), medium-energy general purpose (MEGP), and low-energy high resolution (LEHR), respectively. In addition, three ordered subset expectation maximization (OSEM) algorithms were investigated: attenuation-corrected OSEM (A-OSEM); attenuation and dual- or triple-energy window scatter-corrected OSEM (AS-OSEM); and attenuation, scatter, and collimator-detector response-corrected OSEM (ASC-OSEM), where the latter utilized Monte Carlo-based reconstruction. Uniformity corrections, using intrinsic and extrinsic correction maps, were also investigated. Image quality was assessed by estimated recovery coefficients (RC), noise, and signal-to-noise ratio (SNR). Sensitivity was determined using a circular flat phantom. RESULTS:The best RC and SNR were obtained at an energy window between 67.1 and 82.1?keV. Ring artifacts, caused by non-uniformity, were removed with extrinsic uniformity correction for the energy window between 67.1 and 82.1?keV, but not with intrinsic correction. Analyzing the lower energy window between 48.9 and 62.9?keV, the ring artifacts remained after uniformity corrections. The recovery was similar for the different collimators when using a specific OSEM reconstruction. Recovery and SNR were highest for ASC-OSEM, followed by AS-OSEM and A-OSEM. When using the optimized parameter setting, the resolution of 161Tb was higher than for 177Lu (8.4 ± 0.7 vs. 10.4 ± 0.6?mm, respectively). The sensitivities for 161Tb and 177Lu were 7.41 and 8.46?cps/MBq, respectively. CONCLUSION:SPECT with high resolution is feasible with 161Tb; however, extrinsic uniformity correction is recommended to avoid ring artifacts. The LEHR collimator was the best choice of the three tested to obtain a high-resolution image. Due to the complex emission spectrum of low-energy photons, window-based scatter correction had a minor impact on the image quality compared to using attenuation correction only. On the other hand, performing attenuation, scatter, and collimator-detector correction clearly improved image quality. Based on these data, SPECT-based dosimetry for 161Tb-labeled radiopharmaceuticals is feasible.

Project description:UNLABELLED:Spatial and temporal coregistration of nuclear and optical images can enable the fusion of the information from these complementary molecular imaging modalities. A critical challenge is in integrating the optical and nuclear imaging hardware. Flexible fiber-based fluorescence-mediated tomography (FMT) systems provide a viable solution. The various bore sizes of small-animal nuclear imaging systems can potentially accommodate the FMT fiber imaging arrays. In addition, FMT imaging facilitates coregistration of the nuclear and optical contrasts in time. Herein, we combine a fiber-based FMT system with a preclinical SPECT/CT platform. Feasibility of in vivo imaging is demonstrated by tracking a monomolecular multimodal imaging agent (MOMIA) during transport from the forepaw to the axillary lymph node region of a rat. METHODS:The fiber-based, video-rate FMT imaging system is composed of 12 sources (785- and 830-nm laser diodes) and 13 detectors. To maintain high temporal sampling, the system simultaneously acquires ratio-metric data at each detector. A 3-dimensional finite element model derived from CT projections provides anatomically based light propagation modeling. Injection of a MOMIA intradermally into the forepaw of rats provided spatially and temporally coregistered nuclear and optical contrasts. FMT data were acquired concurrently with SPECT and CT data. The incorporation of SPECT data as a priori information in the reconstruction of FMT data integrated both optical and nuclear contrasts. RESULTS:Accurate depth localization of phantoms with different thicknesses was accomplished with an average center-of-mass error of 4.1 ± 2.1 mm between FMT and SPECT measurements. During in vivo tests, fluorescence and radioactivity from the MOMIA were colocalized in spatially coincident regions with an average center-of-mass error of 2.68 ± 1.0 mm between FMT and SPECT for axillary lymph node localization. Intravital imaging with surgical exposure of the lymph node validated the localization of the optical contrast. CONCLUSION:The feasibility of integrating a fiber-based, video-rate FMT system with a commercial preclinical SPECT/CT platform was established. These coregistered FMT and SPECT/CT results with MOMIAs may facilitate the development of the next generation of preclinical and clinical multimodal optical-nuclear platforms for a broad array of imaging applications and help elucidate the underlying biologic processes relevant to cancer diagnosis and therapy monitoring.

Dataset Information

SPECT/CT Imaging of Mycobacterium tuberculosis Infection with [125I]anti-C3d mAb.

Publications

SPECT/CT Imaging of Mycobacterium tuberculosis Infection with [<sup>125</sup>I]anti-C3d mAb.

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