Hepatic technetium Tc 99m-labeled sestamibi elimination rate and ABCB1 (MDR1) genotype as indicators of ABCB1 (P-glycoprotein) activity in patients with cancer.
Clin Pharmacol Ther
; 77(1): 33-42, 2005 Jan.
Article
em En
| MEDLINE
| ID: mdl-15637529
ABSTRACT
BACKGROUND AND OBJECTIVE:
The adenosine triphosphate-binding cassette transporter ABCB1 (P-glycoprotein) mediates terminal excretion of many chemotherapeutic agents, and variable ABCB1 activity may be an important contributor to interpatient variability in the clearance of chemotherapeutic agents. Our objective was to determine the elimination constant (kH) for hepatic elimination of technetium Tc 99m-labeled sestamibi (99mTc-MIBI) in patients with cancer and to compare this putative indicator of ABCB1 phenotype with clinical features and common ABCB1 genetic variants.METHODS:
99mTc-MIBI kH was determined from the time-dependent elimination profile of 99mTc-MIBI over a 90-minute hepatic scanning period in 66 patients with cancer. Single nucleotide polymorphisms (SNPs) in ABCB1 exons 12 (C1236T), 21 (G2677T/A), and 26 (C3435T) were documented by polymerase chain reaction-restriction fragment length polymorphism analysis.RESULTS:
There was a 12-fold variation in 99mTc-MIBI kH across the cohort, which was not correlated with sex, age, conventional liver function test results, previous chemotherapy treatment, or history of liver metastasis. Mean 99mTc-MIBI kH was significantly reduced in patients with SNPs in exons 21 and 26 such that mean 99mTc-MIBI kH was 1.90 times (95% confidence interval, 1.14-2.66; P = .02) and 2.21 times (95% confidence interval, 1.47-2.97; P < .01) higher in subjects homozygous for the wild-type alleles than in those homozygous for these SNPs, respectively.CONCLUSION:
Hepatic elimination of 99mTc-MIBI is a potential in vivo probe of hepatic ABCB1 activity that is significantly associated with the presence of common SNPs in ABCB1. 99mTc-MIBI hepatic scanning may provide a useful pretreatment indicator of ABCB1-mediated drug clearance in cancer patients.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tecnécio Tc 99m Sestamibi
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Compostos Radiofarmacêuticos
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Genes MDR
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Fígado
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Neoplasias
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Antineoplásicos
Limite:
Adult
/
Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Austrália