Hepatic technetium Tc 99m?labeled sestamibi elimination rate and () genotype as indicators of ABCB1 (P-glycoprotein) activity in patients with cancer

Wong, Mark; Evans, Scott; Rivory, Laurent P.; Hoskins, Janelle M.; Mann, Graham J.; Farlow, David; Clarke, Christine L.; Balleine, Rosemary L.; Gurney, Howard

doi:10.1016/j.clpt.2004.09.002

Cited by 53 publications

(37 citation statements)

References 38 publications

(62 reference statements)

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“…This finding is contradictory to reports showing lower mRNA and protein levels when a homozygous T allele for ABCB1 3435C > T was present (75), and to the findings of others who observed a decreased hepatic 99m TC-MIBI elimination rate, a phenotypic marker for ABCB1-mediated drug clearance, in patients with the TTT haplotype (76). In addition, in CML patients, a TTT-haplotype was associated with higher imatinib trough levels (77).…”

Section: Integrating Knowledge Of Transporters In Improving Imatinib contrasting

confidence: 56%

Drug Transporters and Imatinib Treatment: Implications for Clinical Practice

Eechoute

Sparreboom

Burger

et al. 2011

Clinical Cancer Research

139

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Imatinib mesylate is approved for the treatment of chronic myeloid leukemia (CML) and advanced gastrointestinal stromal tumors (GIST). Unfortunately, in the course of treatment, disease progression occurs in the majority of patients with GIST. Lowered plasma trough levels of imatinib over time potentially cause disease progression, a phenomenon known as "acquired pharmacokinetic drug resistance." This outcome may be the result of an altered expression pattern or activity of drug transporters. To date, the role of both efflux transporters (ATP-binding cassette transporters, such as ABCB1 and ABCG2) and uptake transporters [solute carriers such as organic cation transporter 1 (OCT1) and organic anion transporting polypeptide 1A2 (OATP1A2)] in imatinib pharmacokinetics and pharmacodynamics has been studied. In vitro experiments show a significant role of ABCB1 and ABCG2 in cellular uptake and retention of imatinib, although pharmacokinetic and pharmacogenetic data are still scarce and contradictory. ABCB1 and ABCC1 expression was shown in GIST, whereas ABCB1, ABCG2, and OCT1 were found in mononuclear cells in CML patients. Several studies have reported a clinical relevance of tumor expression or activity of OCT1 in CML patients. Further (clinical) studies are required to quantify drug transporter expression over time in organs involved in imatinib metabolism, as well as in tumor tissue. In addition, more pharmacogenetic studies will be needed to validate associations.

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Section: Integrating Knowledge Of Transporters In Improving Imatinib contrasting

confidence: 56%

Drug Transporters and Imatinib Treatment: Implications for Clinical Practice

Eechoute

Sparreboom

Burger

et al. 2011

Clinical Cancer Research

139

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“…on April 30, 2019. by guest www.bloodjournal.org From those previously reported by Cascorbi et al (P ϭ .3, 1236CϾT; P ϭ .3, 2677GϾT/A; P ϭ .95, 3435CϾT). 10 Three variants appeared in partial linkage disequilibrium, as already reported, 14 and were organized in 7 haplotypes in our cohort ( Figure 1A). …”

Section: Mdr1 Polymorphisms 2025mentioning

confidence: 58%

Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia

Dulucq

Bouchet

Turcq

et al. 2008

Blood

216

144

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Despite the excellent efficacy of imatinib in chronic myeloid leukemia (CML), the response in patients is heterogeneous, which may in part be caused by pharmacogenetic variability. Imatinib has been reported to be a substrate of the P-glycoprotein pump. In the current study, we focused on the ABCB1 (MDR1) genotype. We analyzed the 3 most relevant single nucleotide polymorphisms of MDR1 in 90 CML patients treated with imatinib. Among the patients homozygous for allele 1236T, 85% achieved a major molecular response versus 47.7% for the other genotypes (P = .003). For the 2677G>T/A polymorphism, the presence of G allele was associated with worse response (77.8%, TT/TA; vs 47.1%, GG/GA/GT; P = .018). Patients with 1236TT genotype had higher imatinib concentrations. One of the haplotypes (1236C-2677G-3435C) was statistically linked to less frequent major molecular response (70% vs 44.6%; P = .021). Hence, we demonstrated the usefulness of these single nucleotide polymorphisms in the identification of CML who may or may not respond optimally to imatinib.

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“…Bandur et al [53] reported that wild type haplotype of these three SNPs increases the risk of acute rejection of the graft in renal transplant patients. Some clinical studies have shown that 1236T-2677T-3435T haplotype is associated with reduced P-gp expression and activity [54], and in this manner Panczyk et al [55] confirmed greater risk for colorectal cancer development in population with TTT haplotype. Sai et al [56] associated this mutant haplotype with poorer irinotecan clearance in various cancers.…”

Section: Discussionmentioning

confidence: 81%

Genotype Variability and Haplotype Profile of Abcb1 (Mdr1) Gene Polymorphisms in Macedonian Population

Naumovska

Nestorovska

Sterjev

et al. 2014

Prilozi

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The aim of this study was to evaluate the most common ABCB1 (MDR1, P-glycoprotein) polymorphisms in the population of R. Macedonia and compare the allele and haplotype frequencies with the global geographic data reported from different ethnic populations. The total of 107 healthy Macedonian individuals from the general population was included. Genotypes for the ABCB1 for three polymorphisms C1236T [rs1128503], G2677A/T [rs2032582] and C3435T [rs1045642] were analyzed by Real-Time PCR. Obtained allele frequencies for these three SNPs were similar to those observed in other European Caucasians. The detected genotype frequencies were 33.6% for 1236CC, 44.9% for 1236CT and 21.5% for 1236TT in exon 12; 32.7%, 44.9% and 22.4% for 2677GG, 2677GT and 2677GT consecutively in exon 21; and 25.2% for 3435CC, 52.3% for 3435CT and 22.5% for 3435TT in exon 26.Strong LD was observed in our study among all = 0.859, r 2 = 0.711). Eight different haplotypes were identified and the most prominent was the CGC haplotype (45.3%). Our study was the first to have documented the distribution of ABCB1 alleles, genotypes and haplotypes in the population of R. Macedonia. The obtained results can help in the prediction of different response to the drugs that are P-glycoprotein substrates. Additionally, in the era of individualized medicine the determination of the P-glycoprotein genotype might be a good predictive marker for determination of the subpopulations with higher risk to certain diseases.

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Hepatic technetium Tc 99m?labeled sestamibi elimination rate and () genotype as indicators of ABCB1 (P-glycoprotein) activity in patients with cancer

Abstract: 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.

Cited by 53 publications

References 38 publications

Drug Transporters and Imatinib Treatment: Implications for Clinical Practice

Drug Transporters and Imatinib Treatment: Implications for Clinical Practice

Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia

Genotype Variability and Haplotype Profile of Abcb1 (Mdr1) Gene Polymorphisms in Macedonian Population

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