The cellular basis of increased PET hypoxia tracer uptake in focal cerebral ischemia with comparison between [¹⁸F]FMISO and [⁶⁴Cu]CuATSM

Abstract

PET hypoxia imaging can assess tissue viability in acute ischemic stroke (AIS). [18F]FMISO is an established tracer but requires substantial accumulation time, limiting its use in hyperacute AIS. [64Cu]CuATSM requires less accumulation time and has shown promise as a hypoxia tracer. We compared these tracers in a M2-occlusion model (M2CAO) with preserved collateral blood flow. Rats underwent M2CAO and [18F]FMISO ( n = 12) or [64Cu]CuATSM ( n = 6) examinations. [64Cu]CuATSM animals were also examined with MRI. Pimonidazole was used as a surrogate for [18F]FMISO in an immunofluorescence analysis employed to profile levels of hypoxia in neurons (NeuN) and astrocytes (GFAP). There was increased [18F]FMISO uptake in the M2CAO cortex. No increase in [64Cu]CuATSM activity was found. The pimonidazole intensity of neurons and astrocytes was increased in hypoxic regions. The pimonidazole intensity ratio was higher in neurons than in astrocytes. In the majority of animals, immunofluorescence revealed a loss of astrocytes within the core of regions with increased pimonidazole uptake. We conclude that [18F]FMISO is superior to [64Cu]CuATSM in detecting hypoxia in AIS, consistent with an earlier study. [18F]FMISO may provide efficient diagnostic imaging beyond the hyperacute phase. Results do not provide encouragement for the use of [64Cu]CuATSM in experimental AIS.

Relationship between preoperative hemoglobin levels and length of stay in elderly patients with hip fractures: A retrospective cohort study

“…Ultimately, it decreases adenosine triphosphate concentrations and causes cell death. [ 43 , 44 ] Cheng Q et al have demonstrated a positive correlation between endothelial progenitor cells (EPCs) and bone mass. [ 45 ] EPCs are capable of secreting bone morphogenetic proteins and other osteoblasts, which promote osteoblast proliferation and differentiation, thus accelerating fracture healing.…”

Timing of hypoxia PET/CT imaging after 18F-fluoromisonidazole injection in non-small cell lung cancer patients

“…Precursor (1-(2′-Nitro-1′-imidazolyl)-2- O -tetrahydropyranyl-3- O -toluenesulfonyl-propanediol, NITTP) was used from Advanced Biochemical Compounds (ABX) and the synthesis of FMISO was performed on a FASTlab synthesis module (GE Healthcare) according to the manufacturer’s instructions. The product was then sterilized by filtration through a Millex-GV 0.22 µm sterile filter (Merck Millipore) 35 .…”

[64Cu]Cu-ATSM: an emerging theranostic agent for cancer and neuroinflammation

“…[ 64 Cu]Cu-ATSM may have enhanced BBB penetration over [ 18 F]FAZA which is cleared from the urinary system [64,65]. [ 64 Cu]Cu-ATSM had higher uptake in the hypoxia tissues and more rapid washout in normoxic cells than [ 18 F]fluoromisonidazole ([ 18 F]FMISO), the latter requiring at least 2-h equilibrium before scanning is commenced [39,45,66]. However, Little et al found that [ 18 F] FMISO but not [ 64 Cu]Cu-ATSM or [ 64 Cu]Cu-ATSE identified hypoxic regions in acute ischemic stroke models [66], validating the negative results previously reported [67].…”

“…[ 64 Cu]Cu-ATSM had higher uptake in the hypoxia tissues and more rapid washout in normoxic cells than [ 18 F]fluoromisonidazole ([ 18 F]FMISO), the latter requiring at least 2-h equilibrium before scanning is commenced [39,45,66]. However, Little et al found that [ 18 F] FMISO but not [ 64 Cu]Cu-ATSM or [ 64 Cu]Cu-ATSE identified hypoxic regions in acute ischemic stroke models [66], validating the negative results previously reported [67]. So far, nitroimidazole-derived tracers, such as [ 18 F]FMISO and the sugar-coupled tracer [ 18 F]FAZA, are still the prime contenders in imaging hypoxia [68].…”