Abstract:
PURPOSE:Multidrug resistance (MDR) impedes cancer treatment. Two efflux transporters from the ATP-binding cassette (ABC) family, ABCB1 and ABCG2, may contribute to MDR by restricting the entry of therapeutic drugs into tumor cells. Although a higher expression of these transporters has been correlated with an unfavorable response to chemotherapy, transporter expression does not necessarily correlate with function. In this study, we characterized the pharmacological properties of [18F]AVT-011, a new PET radiotracer for imaging transporter-mediated MDR in tumors. METHODS:AVT-011 was radiolabeled with 18F and evaluated with PET imaging in preclinical models. Transport of [18F]AVT-011 by ABCB1 and/or ABCG2 was assessed by measuring its uptake in the brains of wild-type, Abcb1a/b-/-, and Abcg2-/- mice at baseline and after administration of the ABCB1 inhibitor tariquidar (n = 5/group). Metabolism and biodistribution of [18F]AVT-011 were also measured. To measure ABCB1 function in tumors, we performed PET experiments using both [18F]AVT-011 and [18F]FDG in mice bearing orthotopic breast tumors (n = 7-10/group) expressing clinically relevant levels of ABCB1. RESULTS:At baseline, brain uptake was highest in Abcb1a/b-/- mice. After tariquidar administration, brain uptake increased 3-fold and 8-fold in wild-type and Abcg2-/- mice, respectively, but did not increase further in Abcb1a/b-/- mice. At 30 min after injection, the radiotracer was > 90% in its parent form and had highest uptake in organs of the hepatobiliary system. Compared with that in drug-sensitive tumors, uptake of [18F]AVT-011 was 32% lower in doxorubicin-resistant tumors with highest ABCB1 expression and increased by 40% with tariquidar administration. Tumor uptake of [18F]FDG did not significantly differ among groups. CONCLUSION:[18F]AVT-011 is a dual ABCB1/ABCG2 substrate radiotracer that can quantify transporter function at the blood-brain barrier and in ABCB1-expressing tumors, making it potentially suitable for clinical imaging of ABCB1-mediated MDR in tumors.
journal_name
Eur J Nucl Med Mol Imagingauthors
Kannan P,Füredi A,Dizdarevic S,Wanek T,Mairinger S,Collins J,Falls T,van Dam RM,Maheshwari D,Lee JT,Szakács G,Langer Odoi
10.1007/s00259-019-04589-wsubject
Has Abstractpub_date
2020-07-01 00:00:00pages
2026-2035issue
8eissn
1619-7070issn
1619-7089pii
10.1007/s00259-019-04589-wjournal_volume
47pub_type
杂志文章abstract:PURPOSE:To determine whether the metabolic features of breast tumours differ among molecular subtypes. METHODS:This prospective study included 168 women diagnosed with locally advanced breast cancer. PET/CT was requested in the initial staging before neoadjuvant treatment (multicentre study, FISCAM grant). All patient...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-013-2418-7
更新日期:2013-09-01 00:00:00
abstract:PURPOSE:Radionuclide renography with angiotensin converting enzyme (ACE) inhibition plays an important role in the diagnosis of haemodynamically significant renal artery stenosis. Angiotensin receptor antagonists inhibit the renin angiotensin system at different levels from ACE inhibitors by selectively blocking the bi...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 临床试验,杂志文章
doi:10.1007/s00259-005-1789-9
更新日期:2005-09-01 00:00:00
abstract:PURPOSE:Prostate stem cell antigen (PSCA), a cell surface glycoprotein expressed in normal human prostate and bladder, is over-expressed in the majority of localized prostate cancer and most bone metastases. We have previously shown that the hu1G8 minibody, a humanized anti-PSCA antibody fragment (single-chain Fv-C(H)3...
journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-010-1433-1
更新日期:2010-08-01 00:00:00
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journal_title:European journal of nuclear medicine and molecular imaging
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journal_title:European journal of nuclear medicine and molecular imaging
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更新日期:2010-03-01 00:00:00
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更新日期:2006-03-01 00:00:00
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更新日期:2013-06-01 00:00:00
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journal_title:European journal of nuclear medicine and molecular imaging
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更新日期:2019-10-01 00:00:00
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pub_type: 杂志文章,meta分析
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更新日期:2011-11-01 00:00:00
abstract::Primary treatment of differentiated thyroid carcinoma consists of total thyroidectomy followed by ablation of thyroid tissue remnants and possible metastases by means of radioactive iodine. After complete destruction of remnants, metastases or recurrence can be detected by measurement of the serum thyroglobulin level ...
journal_title:European journal of nuclear medicine and molecular imaging
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更新日期:2002-06-01 00:00:00
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journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 临床试验,杂志文章
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journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
doi:10.1007/s00259-003-1439-z
更新日期:2004-05-01 00:00:00
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journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
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更新日期:2016-11-01 00:00:00
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journal_title:European journal of nuclear medicine and molecular imaging
pub_type: 杂志文章
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更新日期:2008-09-01 00:00:00
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pub_type: 杂志文章
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更新日期:2009-03-01 00:00:00