Subject(s)
Diplopia/diagnosis , Maxillary Sinus Neoplasms/diagnosis , Maxillary Sinus Neoplasms/therapy , Mouth Breathing/diagnosis , Plasmacytoma/diagnosis , Plasmacytoma/therapy , Diagnosis, Differential , Diplopia/etiology , Diplopia/prevention & control , Humans , Male , Maxillary Sinus/diagnostic imaging , Maxillary Sinus Neoplasms/complications , Middle Aged , Mouth Breathing/etiology , Mouth Breathing/prevention & control , Plasmacytoma/complicationsABSTRACT
Based on a high affinity to the enzyme estrone sulfatase (ES), 16alpha-[18F]fluoroestradiol-3,17beta-disulfamate ([18F]FESDS) has been suggested as a potential PET radiotracer for imaging steroid-dependent breast tumours. The distribution of [18F]FESDS was studied in rats, tumour-bearing nude mice and piglets. In all species evidence for binding to a second target, the enzyme carbonic anhydrase (CA), was obtained. ES and CA inhibitors significantly reduced the radiotracer uptake in various organs but not in tumours. It is concluded that [18F]FESDS binds to ES and CA in vivo but this binding is not strong enough to allow tumour imaging with positron emission tomography (PET).
Subject(s)
Estradiol/analogs & derivatives , Fluorine Radioisotopes , Neoplasms, Experimental/diagnostic imaging , Radiopharmaceuticals , Animals , Breast Neoplasms/diagnostic imaging , Estradiol/chemical synthesis , Estradiol/pharmacokinetics , Female , Fluorine Radioisotopes/pharmacokinetics , Humans , Mice , Mice, Nude , Neoplasm Transplantation , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Rats , Rats, Wistar , Swine , Tissue Distribution , Tomography, Emission-Computed , Transplantation, Heterologous , Tumor Cells, CulturedABSTRACT
16Alpha-fluoroestradiol-3,17beta-disulfamate (FESDS) strongly inhibits estrone sulfatase (ES), an enzyme which is also present in the brain. The enzyme is probably involved in important regulatory functions of neurosteroids which may be disturbed in certain brain diseases. In the present study, [18F]FESDS was used to measure the amount of ES in various rat brain regions using quantitative in vitro autoradiography. The obtained values vary between 0.29 pmol (mg protein)(-1) (pons) and 11.5 pmol (mg protein)(-1) (striatum). They are positively correlated with the enzyme activity measured in homogenates of the corresponding regions. Because this radiotracer binds also to carbonic anhydrase in the brain it is only of limited use for in vivo imaging studies.
Subject(s)
Brain/enzymology , Estradiol/pharmacokinetics , Fluorine Radioisotopes , Sulfatases/metabolism , Adenocarcinoma , Animals , Autoradiography/methods , Breast Neoplasms , Estradiol/analogs & derivatives , Female , Humans , Kinetics , Organ Specificity , Rats , Reverse Transcriptase Polymerase Chain Reaction , Sulfatases/genetics , Transcription, Genetic , Tumor Cells, CulturedABSTRACT
A hyaluronic acid splitting enzyme of Streptococcus agalactiae was characterized by splitting mechanism, Michaelis-constant and inhibition type for sulfated hyaluronic acid: The enzyme splits hyaluronic acid as a hyaluronate lyase [EC 4.2.2.1]. The Km = 8 x 10(-4) mg ml-1 was determined with the influence of substrate inhibition constant Kiu = 2 x 10(-6) mg ml-1. Sulfated hyaluronic acid inhibits the enzyme in a partially non-competitive way. The inhibition constant is Ki = 5.47 x 10(-4) mg ml-1. The GBS-hyaluronate lyase cleaves hyaluronic acid as an endoglycosidase. The work is related with the intention to establish a hyaluronate lyase of microbial origin as a therapeutical enzyme replacing bovine hyaluronidase.
