Dataset Information

SPECT Imaging of Muscle Injury with [99mTc]MDP in a Mouse Model of Muscular Dystrophy.

ABSTRACT: PURPOSE:Tc-99m methylene diphosphonate ([99mTc]MDP) is an in vivo bone imaging agent that also accumulates in injured skeletal muscle cells. The objective of this study was to investigate if [99mTc]MDP could be used to detect muscle injury in the mdx mouse model of Duchenne muscular dystrophy (DMD). PROCEDURES:Static whole-body single-photon emission computed tomography/computed tomography (CT) scans were acquired at 2 h post-injection of [99mTc]MDP in two cohorts of animals at different sites: one cohort of mice at 6, 15, and 19 weeks of age, and a separate cohort at 16 weeks. The second cohort was also imaged with high-resolution CT at 8 weeks. RESULTS:mdx mice had higher [99mTc]MDP uptake and significantly higher [99mTc]MDP concentrations in muscle than controls. CONCLUSIONS:Higher uptake of [99mTc]MDP in muscle of mdx mice agrees with histological reports of muscle calcification in mdx mice, and suggests the potential translational use of [99mTc]MDP imaging for tracking DMD progression and therapeutic response.

SUBMITTER: Gaut C

PROVIDER: S-EPMC7250810 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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SPECT Imaging of Muscle Injury with [<sup>99m</sup>Tc]MDP in a Mouse Model of Muscular Dystrophy.

Gaut Carolynn C Sullivan Jenna M JM Biscaro Barbara B Soares Edward J EJ Nicholson Katharine K Hoppin Jack J Verma Ajay A

Molecular imaging and biology 20200601 3

<h4>Purpose</h4>Tc-99m methylene diphosphonate ([<sup>99m</sup>Tc]MDP) is an in vivo bone imaging agent that also accumulates in injured skeletal muscle cells. The objective of this study was to investigate if [<sup>99m</sup>Tc]MDP could be used to detect muscle injury in the mdx mouse model of Duchenne muscular dystrophy (DMD).<h4>Procedures</h4>Static whole-body single-photon emission computed tomography/computed tomography (CT) scans were acquired at 2 h post-injection of [<sup>99m</sup>Tc]MD ...[more]

PMID: 31286350

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Project description:Authors' goal is to evaluate the performance of simultaneous (99m)Tc-MDP/(123)I-MIBG tumor imaging with fast Monte-Carlo (MC) based joint iterative reconstruction as compared to sequential (99m)Tc-MDP and (123)I-MIBG tumor imaging.Noise-free (99m)Tc and (123)I SPECT projections were acquired separately using an anthropomorphic torso phantom modified to include a fillable tube around the lungs to mimic ribs. Additionally, (99m)Tc and (123)I projections were acquired separately using a 1-cm spherical "tumor" placed at various distances from one detector. Tumor-present data were generated by adding tumor projections to the torso phantom data, which were scaled to the total counts in typical clinical studies. Twenty-five noise realizations were generated by adding Poisson noise to the projection data for each radionuclide. Dual-radionuclide data were synthesized by summing the (99m)Tc and (123)I projections. Image reconstruction was performed using: (1) SR-OSEM, ordered subset expectation maximization (OSEM) without scatter correction (SC) using single-radionuclide (SR) data; (2) SR-MC-OSEM, OSEM with a fast MC-based SC using SR data; (3) DR-OSEM, OSEM without SC using dual-radionuclide (DR) data; and (4) DR-MC-JOSEM, joint OSEM with a fast MC-based SC using DR data. Ten (99m)Tc-MDP and ten (123)I-MIBG data sets, which had tumors mathematically inserted, were also used to evaluate the performance of authors' approach. For the phantom study, relative bias and relative standard deviation of tumor uptake were computed for each tumor using the tumor uptake in the noise-free single-radionuclide images, which were reconstructed by SR-MC-OSEM, as the gold standard. For both the phantom and constructed patient studies, mean contrast and standard deviation of contrast were computed for each tumor for both the single- and dual-radionuclide images. Additionally, contrast recovery was computed as the ratio between mean contrast and the mean contrast for SR-MC-OSEM.For the phantom study, DR-MC-JOSEM yielded 2.7% on average relative bias of tumor uptake using the images, which were reconstructed from the noise-free SR data with SR-MC-OSEM, as the gold-standard. For both the phantom and constructed patient studies, DR-MC-JOSEM yielded 94.7% and 95.2% tumor contrast recovery on average using SR-MC-OSEM as the reference, in the phantom and constructed patient studies, respectively. DR-MC-JOSEM yielded comparable relative standard deviation of bias and standard deviation of contrast to SR-MC-OSEM.Simultaneous (99m)Tc-MDP/(123)I-MIBG tumor imaging using authors' dual-radionuclide reconstruction approach yielded comparable image quality to sequential (99m)Tc-MDP and (123)I-MIBG imaging. For patients who need to undergo both scans, authors' approach offers perfectly registered dual-tracer images under identical conditions without compromising image quality, and reduces the imaging cost while increasing patient throughput.

Project description:BackgroundDuchenne muscular dystrophy (DMD) is an incurable disease, caused by the mutations in the DMD gene, encoding dystrophin, an actin-binding cytoskeletal protein. Lack of functional dystrophin results in muscle weakness, degeneration, and as an outcome cardiac and respiratory failure. As there is still no cure for affected individuals, the pharmacological compounds with the potential to treat or at least attenuate the symptoms of the disease are under constant evaluation. The pleiotropic agents, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, have been suggested to exert beneficial effects in the mouse model of DMD. On the other hand, they were also reported to induce skeletal-muscle myopathy. Therefore, we decided to verify the hypothesis that simvastatin may be considered a potential therapeutic agent in DMD.MethodsSeveral methods including functional assessment of muscle function via grip strength measurement, treadmill test, and single-muscle force estimation, enzymatic assays, histological analysis of muscle damage, gene expression evaluation, and immunofluorescence staining were conducted to study simvastatin-related alterations in the mdx mouse model of DMD.ResultsIn our study, simvastatin treatment of mdx mice did not result in improved running performance, grip strength, or specific force of the single muscle. Creatine kinase and lactate dehydrogenase activity, markers of muscle injury, were also unaffected by simvastatin delivery in mdx mice. Furthermore, no significant changes in inflammation, fibrosis, and angiogenesis were noted. Despite the decreased percentage of centrally nucleated myofibers in gastrocnemius muscle after simvastatin delivery, no changes were noticed in other regeneration-related parameters. Of note, even an increased rate of necrosis was found in simvastatin-treated mdx mice.ConclusionIn conclusion, our study revealed that simvastatin does not ameliorate DMD pathology.

Dataset Information

SPECT Imaging of Muscle Injury with [99mTc]MDP in a Mouse Model of Muscular Dystrophy.

Publications

SPECT Imaging of Muscle Injury with [<sup>99m</sup>Tc]MDP in a Mouse Model of Muscular Dystrophy.

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