Linked Life Data

15359928

Source:http://linkedlifedata.com/resource/pubmed/id/15359928

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-9-13
pubmed:abstractText
Recently, 5-[123I]iodo-3-(2(S)-azetidinylmethoxy)pyridine ([123I]5IA) was developed as a ligand for imaging the nicotinic acetylcholine receptor (nAChR) in human brain using single photon emission computed tomography (SPECT). In the present study, the toxicity and radiation absorbed dose of [123I]5IA were investigated. Behavior and physiological parameters were examined in mice and rats after administration of 5IA. There were no changes in these parameters in animals administered 1 microg/kg of 5IA or less, indicating that the no observed effect level (NOEL) of 5IA was 1 microg/kg. [123I]5IA was then administered to healthy human subjects and serial whole-body images were acquired over 24 hr. Initially, high levels of radioactivity were observed in the liver and urinary bladder and moderate levels in the lungs, kidneys, and brain. Whole brain activity at 1 hr was 4.6 +/- 0.4% of the injected dose and this value gradually decreased with time. The majority (-75%) of the radioactivity was excreted in urine within 24 hr, and less than 1% remained in all organs tested. The biological half-life of [1231]51A averaged 7.2 +/- 4.0 hr. Based on the biodistribution data, radiation absorbed doses were estimated using MIRDOSE 3.1 software with the dynamic bladder model and the ICRP gastrointestinal (GI) tract model. Consequently, the effective dose equivalent was estimated to be 30 +/- 1.4 microSv/MBq, which is an acceptable radiation burden. Having determined the safety of this compound, we performed SPECT imaging in a healthy human subject using 171 MBq of [123I]5IA. SPECT images clearly revealed a cerebral distribution of radioactivity that was consistent with the known distribution of central nAChRs in humans. These results suggest that [123I]5IA is a promising ligand for imaging nAChRs in humans, with an acceptable dosimetry and pharmacological safety at the dose required for adequate SPECT imaging.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0914-7187
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
337-44
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15359928-Adult, pubmed-meshheading:15359928-Aged, pubmed-meshheading:15359928-Animals, pubmed-meshheading:15359928-Azetidines, pubmed-meshheading:15359928-Body Burden, pubmed-meshheading:15359928-Brain, pubmed-meshheading:15359928-Humans, pubmed-meshheading:15359928-Male, pubmed-meshheading:15359928-Metabolic Clearance Rate, pubmed-meshheading:15359928-Mice, pubmed-meshheading:15359928-Mice, Inbred ICR, pubmed-meshheading:15359928-Organ Specificity, pubmed-meshheading:15359928-Pyridines, pubmed-meshheading:15359928-Radiation Dosage, pubmed-meshheading:15359928-Radiation Injuries, pubmed-meshheading:15359928-Radiometry, pubmed-meshheading:15359928-Radiopharmaceuticals, pubmed-meshheading:15359928-Rats, pubmed-meshheading:15359928-Rats, Sprague-Dawley, pubmed-meshheading:15359928-Receptors, Nicotinic, pubmed-meshheading:15359928-Relative Biological Effectiveness, pubmed-meshheading:15359928-Species Specificity, pubmed-meshheading:15359928-Tissue Distribution, pubmed-meshheading:15359928-Whole-Body Counting
pubmed:year
2004
pubmed:articleTitle
5-[123I]Iodo-A-85380: assessment of pharmacological safety, radiation dosimetry and SPECT imaging of brain nicotinic receptors in healthy human subjects.
pubmed:affiliation
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
pubmed:publicationType
Journal Article, Clinical Trial, Comparative Study, Research Support, Non-U.S. Gov't