99mTc tricarbonyl glycine monomers, trimers, and pentamers were synthesized and evaluated for their radiolabeling and in vivo distribution characteristics. We synthesized a 99mTc-tricarbonyl precursor with a low oxidation state (I). 99mTc(CO)3(H2O)3 + was then made to react with monomeric and oligomeric glycine for the development of bifunctional chelating sequences for biomolecules. Labeling yields of 99mTc-tricarbonyl glycine monomers and oligomers were checked by high-performance liquid chromatography. The labeling yields of 99mTc-tricarbonyl glycine and glycine oligomers were more than 95%. We evaluated the characteristics of 99mTc-tricarbonyl glycine oligomers by carrying out a lipophilicity test and an imaging study. The octanol-water partition coefficient of 99mTc tricarbonyl glycine oligomers indicated hydrophilic properties. Single-photon emission computed tomography imaging of 99mTc-tricarbonyl glycine oligomers showed rapid renal excretion through the kidneys with a low uptake in the liver, especially of 99mTc tricarbonyl triglycine. Furthermore, we verified that the addition of triglycine to prototype biomolecules (AGRGDS and RRPYIL) results in the improvement of radiolabeling yield. From these results, we conclude that triglycine has good characteristics for use as a bifunctional chelating sequence for a 99mTc-tricarbonyl-based biomolecular imaging probe.
Chromatography, Liquid ; Glycine ; Kidney ; Lifting ; Liver ; Oligopeptides ; Pentamidine ; Tomography, Emission-Computed

Trimethoprim-sulfamethoxazole (TMX-SMZ) is the initial treatment for Pneumocystis jiroveci pneumonia in human immunodeficiency virus (HIV) patients. About 20% of patients do not complete the TMX-SMZ treatment due to treatment failure or adverse reactions. Pentamidine isethionate has been used for P. jiroveci pneumonia as a second-line regimen. Although hypoglycemia is a common adverse effect of pentamidine, pentamidine-induced hypoglycemia has not been reported in Korea. We present an HIV patient with grand mal seizures caused by pentamidine-induced hypoglycemia who was managed successfully with IV dextrose infusion. Mental changes can occur during pentamidine treatment, but hypoglycemia is often ignored and misdiagnosed as epilepsy or stroke. It can result in seizures, coma, and even death. We should be aware of pentamidine-induced hypoglycemia, which can lead to severe neurologic deficits and diabetes mellitus.
Coma ; Diabetes Mellitus ; Epilepsy ; Glucose ; HIV ; Humans ; Hypoglycemia ; Korea ; Neurologic Manifestations ; Pentamidine ; Pneumocystis ; Pneumocystis jirovecii ; Pneumonia ; Seizures ; Stroke ; Treatment Failure ; Trimethoprim, Sulfamethoxazole Drug Combination

BACKGROUND: Wear debris-induced osteolysis leads to periprosthetic loosening and subsequent prosthetic failure. Since excessive osteoclast formation is closely implicated in periprosthetic osteolysis, identification of agents to suppress osteoclast formation and/or function is crucial for the treatment and prevention of wear particle-induced bone destruction. In this study, we examined the potential effect of pentamidine treatment on titanium (Ti) particle-induced osteolysis, and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. METHODS: The effect of pentamidine treatment on bone destruction was examined in Ti particle-induced osteolysis mouse model. Ti particles were implanted onto mouse calvaria, and vehicle or pentamidine was administered for 10 days. Then, calvarial bone tissue was analyzed using micro-computed tomography and histology. We performed in vitro osteoclastogenesis assay using bone marrow-derived macrophages (BMMs) to determine the effect of pentamidine on osteoclast formation. BMMs were treated with 20 ng/mL RANKL and 10 ng/mL macrophage colony-stimulating factor in the presence or absence of pentamidine. Osteoclast differentiation was determined by tartrate-resistant acid phosphatase staining, real-time polymerase chain reaction, and immunofluorescence staining. RESULTS: Pentamidine administration decreased Ti particle-induced osteoclast formation significantly and prevented bone destruction compared to the Ti particle group in vivo. Pentamidine also suppressed RANKL-induced osteoclast differentiation and actin ring formation markedly, and inhibited the expression of nuclear factor of activated T cell c1 and osteoclast-specific genes in vitro. Additionally, pentamidine also attenuated RANKL-mediated phosphorylation of IκBα in BMMs. CONCLUSION: These results indicate that pentamidine is effective in inhibiting osteoclast formation and significantly attenuates wear debris-induced bone loss in mice.
Acid Phosphatase ; Actins ; Animals ; Bone and Bones ; Fluorescent Antibody Technique ; In Vitro Techniques ; Macrophage Colony-Stimulating Factor ; Macrophages ; Mice ; Osteoclasts ; Osteolysis ; Pentamidine ; Phosphorylation ; Real-Time Polymerase Chain Reaction ; Skull ; Titanium