Source:http://linkedlifedata.com/resource/pubmed/id/16631086
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2006-4-24
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pubmed:abstractText |
Bombesin (BBN), an analog of human gastrin-releasing peptide (GRP), binds to the GRP receptor (GRPR) with high affinity and specificity. Overexpression of GRPR has been discovered in mostly androgen-independent human prostate tissues and, thus, provides a potential target for prostate cancer diagnosis and therapy. We have previously demonstrated the feasibility of the positron emission tomography (PET) imaging using 64Cu-1,4,7,10-tetraazadodecane-N,N',N'',N'''-tetraacetic acid (DOTA)-[Lys3]BBN to detect GRPR-positive prostate cancer. In this study, we compared the receptor affinity, metabolic stability, tumor-targeting efficacy, and pharmacokinetics of a truncated BBN analog 64Cu-DOTA-Aca-BBN(7-14) with 64Cu-DOTA-[Lys3]BBN. Binding of each DOTA conjugate to GRPR on PC-3 and 22Rv1 prostate cancer cells was evaluated with competitive binding assay using 125I-[Tyr4]BBN as radioligand. In vivo pharmacokinetics was determined on male nude mice subcutaneously implanted with PC-3 cells. Dynamic microPET imaging was performed to evaluate the systemic distribution of the tracers. Metabolic stability of the tracers in blood, urine, tumor, liver and kidney was studied using high-performance liquid chromatography. The results showed that 125I-[Tyr4]BBN has a K(d) of 14.8+/-0.4 nM against PC-3 cells, and the receptor concentration on PC-3 cell surface is approximately 2.7+/-0.1 x 10(6) receptors per cell. The 50% inhibitory concentration value for DOTA-Aca-BBN(7-14) is 18.4 +/- 0.2 nM, and that for DOTA-[Lys3]BBN is 2.2 +/- 0.5 nM. DOTA-[Lys3]BBN shows a better tumor contrast and absolute tumor activity accumulation compared to DOTA-Aca-BBN(7-14). Studies on metabolic stability for both tracers on organ homogenates showed that 64Cu-DOTA-[Lys3]BBN is relatively stable. This study demonstrated that both tracers are suitable for targeted PET imaging to detect the expression of GRPR in prostate cancer, while 64Cu-DOTA-[Lys3]BBN may have a better potential for clinical translation.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/P50 CA114747,
http://linkedlifedata.com/resource/pubmed/grant/R21 CA102123,
http://linkedlifedata.com/resource/pubmed/grant/R21 EB001785,
http://linkedlifedata.com/resource/pubmed/grant/R24 CA86307,
http://linkedlifedata.com/resource/pubmed/grant/R24 CA93862,
http://linkedlifedata.com/resource/pubmed/grant/U54
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0969-8051
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
33
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
371-80
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:16631086-Adenocarcinoma,
pubmed-meshheading:16631086-Animals,
pubmed-meshheading:16631086-Binding, Competitive,
pubmed-meshheading:16631086-Bombesin,
pubmed-meshheading:16631086-Copper Radioisotopes,
pubmed-meshheading:16631086-Disease Models, Animal,
pubmed-meshheading:16631086-Humans,
pubmed-meshheading:16631086-Male,
pubmed-meshheading:16631086-Mice,
pubmed-meshheading:16631086-Mice, Nude,
pubmed-meshheading:16631086-Positron-Emission Tomography,
pubmed-meshheading:16631086-Prostatic Neoplasms,
pubmed-meshheading:16631086-Receptors, Bombesin,
pubmed-meshheading:16631086-Tissue Distribution
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pubmed:year |
2006
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pubmed:articleTitle |
Comparative in vitro and in vivo evaluation of two 64Cu-labeled bombesin analogs in a mouse model of human prostate adenocarcinoma.
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pubmed:affiliation |
Department of Radiology and Bio-X Program, The Molecular Imaging Program at Stanford (MIPS), Stanford University School of Medicine, Stanford, CA 94305-5484, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
In Vitro,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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