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

Abstract

Purpose: Tc-99m methylene diphosphonate ([ 99m 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 [ 99m Tc]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 [ 99m Tc]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 [ 99m Tc]MDP uptake and significantly higher [ 99m Tc]MDP concentrations in muscle than controls. Conclusions: Higher uptake of [ 99m Tc]MDP in muscle of mdx mice agrees with histological reports of muscle calcification in mdx mice, and suggests the potential translational use of [ 99m Tc]MDP imaging for tracking DMD progression and therapeutic response.

68Ga-bisphosphonates for the imaging of extraosseous calcification by positron emission tomography

“…This consensus is oversimplified and a range of calcium salts may be observed including HAp, apatite, (amorphous) calcium phosphate, whitlockite, calcium oxalate and calcium carbonate 34 . Various studies have demonstrated the presence of calcification in a wide variety of diseases, including atherosclerosis 25 , 29 , 30 , age-related macular degeneration 35 , Alzheimer’s disease 36 , muscular dystrophy 23 , various cancers 21 , 37 , 38 , kidney stones 26 , 27 , 31 and chronic kidney disease (CKD) 39 .…”

68Ga-Bisphosphonates for the Imaging of Extraosseous Calcification by Positron Emission Tomography

“…The prevalence of HAp in bones makes [ 18 F]NaF an excellent tracer for the imaging of bones. On the other hand, reports on the mineral composition of extraosseous calcification (EC), which is defined as "deposition of calcium in tissues outside of bone" [27] and includes conditions such as vascular calcification, are diverse and contradictory [28][29][30][31][32][33][34][35][36][37][38][39][40][41]. For example, often these calcifications are euphemistically called HAp as a blanket term for all forms of apatite or solid calciumcontaining mineral.…”

“…Various studies have demonstrated the presence of calcification in a wide variety of diseases, including atherosclerosis [32, 33, 37-39, 44, 45], age-related macular degeneration [46], Alzheimer's disease [47], muscular dystrophy [30], various cancers [28,[48][49][50][51][52][53][54][55][56], kidney stones [34,35,40,57] and chronic kidney disease (CKD) [58,59]. Nonetheless, [ 18 F]NaF is the only clinically used PET tracer for the imaging of extraosseous calcification [60].…”

“…This consensus is oversimplified and a range of calcium salts may be observed including HAp, apatite, (amorphous) calcium phosphate, whitlockite, calcium oxalate and calcium carbonate [43]. Various studies have demonstrated the presence of calcification in a wide variety of diseases, including atherosclerosis [32, 33, 37-39, 44, 45], age-related macular degeneration [46], Alzheimer’s disease [47], muscular dystrophy [30], various cancers [28, 48-56], kidney stones [34, 35, 40, 57] and chronic kidney disease (CKD) [58, 59].…”

Disturbance of cellular homeostasis as a molecular risk evaluation of human endothelial cells exposed to nanoparticles

“…Four types of NPs were used (Table 1, Fig. 1): the monoclonal antibody, TRASTUZUMAB (PLA/ MMT/TRA) modified with polylactic acetate (PLA) and montmorillonite (MMT), which specifically targets HER2 receptor extracellular domain 15 ; ethylene diamine N,N,N' ,N' tetramethylene phosphonic acid NPs coated with PLA (PLA/EDTMP) 16 , which are used in breast and bone cancer treatment; silicon NPs PLGA/MDP modified with methylene diphosphate (MDP) and coupled to poly lactic-co-glycolic acid (PLGA) 17 , which can be used in scintigraphy; and Pluronic F127 MICELLES (Pluronic F127 Ms), that can be administered dermally 18 , intranasally, or intravenously 19 . HUVEC-STs were used as a cellular model.…”