ABSTRACT
BACKGROUND: Myeloid sarcoma is a rare malignant hematopoietic neoplasm that arises at extramedullary sites. Although myeloid sarcoma may involve any organ, central nervous system (CNS) involvement is exceptionally rare. To date, few case reports and case series have described CNS myeloid sarcoma, the majority of which include peripheral disease. OBSERVATIONS: The authors present an illustrative case of an adult male with acute myeloid leukemia (AML) in remission relapsing with an isolated, diffuse myeloid sarcoma of the cerebellum. Magnetic resonance imaging showed posterior fossa crowding and diffuse enhancement within the cerebellar white matter without an apparent mass lesion. The patient required ventriculostomy due to obstructive hydrocephalus and ultimately suboccipital craniectomy with duraplasty due to posterior fossa compression. An open cerebellar biopsy revealed myeloid sarcoma. Peripheral studies did not meet the criteria for recurrent AML. The patient subsequently received high-dose systemic chemotherapy and has responded well to treatment. LESSONS: Myeloid sarcoma may be a neurosurgical lesion because it has the potential to cause mass effect with obstructive hydrocephalus requiring emergent cerebrospinal fluid diversion and possible decompression. The authors report a rare case of isolated recurrence of AML in the form of diffuse CNS myeloid sarcoma and describe the role of neurosurgery in its diagnosis and treatment.
ABSTRACT
19F magnetic resonance imaging (MRI), an emerging modality in biomedical imaging, has shown promise for in vitro and in vivo preclinical studies. Here we present a series of fluorinated Cu(II)ATSM derivatives for potential use as 19F magnetic resonance agents for sensing cellular hypoxia. The synthesized complexes feature a hypoxia-targeting Cu2+ coordination core, nine equivalent fluorine atoms connected via a variable-length poly(ethylene glycol) linker. Introduction of the fluorine moiety maintains the planar coordination geometry of the Cu2+ center, while the linker length modulates the Cu2+/+ reduction potential, 19F NMR relaxation properties, and lipophilicity. In particular, the 19F NMR relaxation properties were quantitatively evaluated by the Solomon-Bloembergen model, revealing a regular pattern of relaxation enhancement tuned by the distance between Cu2+ and F atoms. Finally, the potential utility of these complexes for sensing reductive environments was demonstrated using both 19F MR phantom imaging and 19F NMR, including experiments in intact live cells.
Subject(s)
Biocompatible Materials/chemistry , Coordination Complexes/chemistry , Copper/chemistry , Fluorine-19 Magnetic Resonance Imaging , Molecular Probes/chemistry , Biocompatible Materials/chemical synthesis , Biocompatible Materials/pharmacology , Cell Hypoxia/drug effects , Cell Survival/drug effects , Coordination Complexes/chemical synthesis , Coordination Complexes/pharmacology , Dose-Response Relationship, Drug , Humans , MCF-7 Cells , Models, Molecular , Molecular Probes/chemical synthesis , Molecular Probes/pharmacology , Molecular Structure , Oxidation-Reduction , Structure-Activity RelationshipABSTRACT
We report a pair of fluorinated, redox-active copper complexes for potential use as (19)F MRI contrast agents for detecting cellular hypoxia. Trifluorinated Cu(II) ATSM-F3 displays the appropriate redox potential for selective accumulation in hypoxic cells and a completely quenched (19)F NMR signal that is "turned on" following reduction to Cu(I). Incubation of cancer cells with CuATSM-F3 resulted in a selective detection of (19)F signal in cells grown under hypoxic conditions.
