| pubmed-article:10344751 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:10344751 | lifeskim:mentions | umls-concept:C0027651 | lld:lifeskim |
| pubmed-article:10344751 | lifeskim:mentions | umls-concept:C0025663 | lld:lifeskim |
| pubmed-article:10344751 | lifeskim:mentions | umls-concept:C0005854 | lld:lifeskim |
| pubmed-article:10344751 | lifeskim:mentions | umls-concept:C0242643 | lld:lifeskim |
| pubmed-article:10344751 | lifeskim:mentions | umls-concept:C0005528 | lld:lifeskim |
| pubmed-article:10344751 | lifeskim:mentions | umls-concept:C2603343 | lld:lifeskim |
| pubmed-article:10344751 | lifeskim:mentions | umls-concept:C1515655 | lld:lifeskim |
| pubmed-article:10344751 | pubmed:issue | 10 | lld:pubmed |
| pubmed-article:10344751 | pubmed:dateCreated | 1999-6-17 | lld:pubmed |
| pubmed-article:10344751 | pubmed:abstractText | Drug resistance is a major cause of chemotherapy failure in cancer treatment. One reason is the overexpression of the drug efflux pump P-glycoprotein (P-gp), involved in multidrug resistance (MDR). In vivo pharmacokinetic analysis of P-gp transport might identify the capacity of modulation by P-gp substrate modulators, such as cyclosporin A. Therefore, P-gp function was measured in vivo with positron emission tomography (PET) and [11C]verapamil as radiolabeled P-gp substrate. Studies were performed in rats bearing tumors bilaterally, a P-gp-negative small cell lung carcinoma (GLC4) and its P-gp-overexpressing subline (GLC4/P-gp). For validation, in vitro and biodistribution studies with [11C]daunorubicin and [11C]verapamil were performed. [11C]Daunorubicin and [11C]verapamil accumulation were higher in GLC4 than in GLC4/P-gp cells. These levels were increased after modulation with cyclosporin A in GLC4/P-gp. Biodistribution studies showed 159% and 185% higher levels of [11C]daunorubicin and [11C]verapamil, respectively, in GLC4 than in GLC4/P-gp tumors. After cyclosporin A, [11C]daunorubicin and [11C]verapamil content in the GLC4/P-gp tumor was raised to the level of GLC4 tumors. PET measurements demonstrated a lower [11C]verapamil content in GLC4/P-gp tumors compared with GLC4 tumors. Pretreatment with cyclosporin A increased [11C]verapamil levels in GLC4/P-gp tumors (184%) and in brains (1280%). This pharmacokinetic effect was clearly visualized with PET. These results show the feasibility of in vivo P-gp function measurement under basal conditions and after modulation in solid tumors and in the brain. Therefore, PET and radiolabeled P-gp substrates may be useful as a clinical tool to select patients who might benefit from the addition of a P-gp modulator to MDR drugs. | lld:pubmed |
| pubmed-article:10344751 | pubmed:language | eng | lld:pubmed |
| pubmed-article:10344751 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10344751 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:10344751 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10344751 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10344751 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10344751 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10344751 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10344751 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10344751 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10344751 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:10344751 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:10344751 | pubmed:month | May | lld:pubmed |
| pubmed-article:10344751 | pubmed:issn | 0008-5472 | lld:pubmed |
| pubmed-article:10344751 | pubmed:author | pubmed-author:VaalburgWW | lld:pubmed |
| pubmed-article:10344751 | pubmed:author | pubmed-author:de VriesE GEG | lld:pubmed |
| pubmed-article:10344751 | pubmed:author | pubmed-author:van der... | lld:pubmed |
| pubmed-article:10344751 | pubmed:author | pubmed-author:FranssenE JEJ | lld:pubmed |
| pubmed-article:10344751 | pubmed:author | pubmed-author:HospersG AGA | lld:pubmed |
| pubmed-article:10344751 | pubmed:author | pubmed-author:WillemsenA... | lld:pubmed |
| pubmed-article:10344751 | pubmed:author | pubmed-author:HendrikseN... | lld:pubmed |
| pubmed-article:10344751 | pubmed:author | pubmed-author:Eriks-FluksLL | lld:pubmed |
| pubmed-article:10344751 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:10344751 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:10344751 | pubmed:volume | 59 | lld:pubmed |
| pubmed-article:10344751 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:10344751 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:10344751 | pubmed:pagination | 2411-6 | lld:pubmed |
| pubmed-article:10344751 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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| pubmed-article:10344751 | pubmed:meshHeading | pubmed-meshheading:10344751... | lld:pubmed |
| pubmed-article:10344751 | pubmed:year | 1999 | lld:pubmed |
| pubmed-article:10344751 | pubmed:articleTitle | A new in vivo method to study P-glycoprotein transport in tumors and the blood-brain barrier. | lld:pubmed |
| pubmed-article:10344751 | pubmed:affiliation | Positron Emission Tomography Center, Department of Medical Oncology, Groningen University Hospital, The Netherlands. | lld:pubmed |
| pubmed-article:10344751 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:10344751 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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