Linked Life Data

16459262

Source:http://linkedlifedata.com/resource/pubmed/id/16459262

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-2-6
pubmed:abstractText
The radioisotopes (186)Re and (188)Re have been extensively investigated for various forms of radiotherapy due to their useful and high-abundance beta particle emissions, low-abundance and imageable gamma-rays, and chemical resemblance to technetium. In addition, (188)Re is available in no-carrier-added (NCA) form from long lived W-188 generators, whereas (186)Re can be produced in large quantities from reactors, although not in NCA form. However, NCA (186)Re can be produced on a cyclotron by a (p,n) reaction on (186)W. The purpose of this study was to compare labeling of the peptide bombesin with these three forms of rhenium radioisotopes. Cyclotron-produced NCA (186)Re was separated radiochemically from enriched (186)W (96.9%) targets using high-purity methyl ethyl ketone (MEK). The resulting (186)Re-MEK was then loaded onto a small alumina column to separate the resulting NCA (186)Re from any remaining (186)W. The experimental levels of impurities associated with (186)Re at the end of the separation process were found to be 5.7 x 10(-6) Ci of (182)Re (0.57%, t(1/2) = 12.7 h) and 1.283 x 10(-5) Ci of (182m)Re (1.28%, t(1/2) = 2.67 days). The radionuclidic purity of the separated (186)Re was found to be 99.6%, whereas the chemical identity was determined by reversed phase high-performance liquid chromatography (RP-HPLC) to be perrhenate ((186)ReO(4)(-)). Generator-produced (188)ReO(4)(-) from a (188)W/(188)Re generator (Oak Ridge National Laboratory) and CA (186)ReO(4)(-) produced from a (185)Re(n,gamma)(186)Re reaction at the University of Missouri Research Reactor (MURR) were used for comparison with the NCA (186)Re in subsequent studies. N(3)S-5-Ava-BBN(7-14)NH(2) conjugates provide flexibility for designing (186,188)Re-labeled conjugates that retain high in vitro and in vivo specificity targeting of GRP receptor-expressing cells. This study showed that the N(3)S-5-Ava-BBN(7-14)NH(2) could be labeled with (186,188)Re following the preconjugation, postmetallation approach. The (186,188)Re(V)O-N(3)S-5-Ava-BBN(7-14)NH(2) complexes were found to form stable complexes following the reduction of perrhenate (Re(VII)O(4)(-)) with stannous chloride at room temperature, as verified by HPLC and stability studies. The radiolabeling yield was found to be >90%. The HPLC chromatograms of (186,188)Re-N(3)S-5-Ava-BBN(7-14)NH(2) complexes revealed two peaks for each conjugate, reflecting the presence of syn- and anti-isomers, which were resolvable by HPLC but re-isomerized on separation. The biodistribution studies showed that the compounds were excreted through the renal and hepatobiliary systems and demonstrated receptor-specific uptake with an average pancreas accumulation of 8.15% ID/g at 1 h postinjection. Administration of cold BBN effectively blocked pancreatic uptake and further reflects the high specificity this conjugate has for the GRP receptors. At low levels of radioactivity, radiolysis effects were not observed. Scale-up may or may not elicit this effect, particularly for the higher energy beta emitter (188)Re. The biodistribution studies demonstrated that the CA and NCA (186,188)Re conjugates behaved similarly, raising the question of whether NCA (186,188)Re is necessary for specific tumor receptor targeting.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0969-8051
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
81-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Preparation of cyclotron-produced 186Re and comparison with reactor-produced 186Re and generator-produced 188Re for the labeling of bombesin.
pubmed:affiliation
Department of Chemistry, University of Missouri-Columbia, 65211, USA.
pubmed:publicationType
Journal Article, Comparative Study, Evaluation Studies