World Journal of Nuclear Medicine

ORIGINAL ARTICLE
Year
: 2012  |  Volume : 11  |  Issue : 2  |  Page : 65--69

18 F-FLT-PET for response evaluation of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with solid tumors


Ingrid M. E. Desar1, Rozemarie Gilles2, Carla M. L. van Herpen1, Anja (J.) N. H. Timmer-Bonte1, Mireille V Cantarini3, Winette T. A. van der Graaf1, Wim J. G. Oyen2 
1 Department of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
2 Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
3 Astra Zeneca, Alderley Park, Macclesfield, USA

Correspondence Address:
Ingrid M. E. Desar
Department of Medical Oncology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500HB Nijmegen
Netherlands

Selumetinib (AZD6244, ARRY-142886) is a potent, selective, uncompetitive inhibitor of MEK 1 / 2, part of the RAF/MEK/ERK protein kinase signal cascade, which is responsible for tumor. This pilot study was used to explore if 18  F-fluoro-l-thymidine (FLT), a thymidine analogue positron emission tomography (PET) tracer and a surrogate marker for proliferation, can be used as an early predictor of response for patients with solid cancers treated with Selumetinib. FLT-PET scans were performed in four patients at baseline and after 2 weeks of treatment with Selumetinib. FLT uptake in tumors was analyzed qualitatively and quantitatively by measuring standard uptake value (SUV) max in regions of interest (ROI). Results were compared to computed tomography (CT) scans (baseline and after 8 weeks), which were evaluated using the response evaluation criteria in solid tumors (RECIST) 1.0 criteria. One patient with melanoma showed both a qualitative and quantitative decrease in FLT uptake associated with a decrease in sum of longest diameter of 12% RECIST on CT evaluation. Another patient who had colorectal carcinoma (CRC) showed a significant increase in FLT uptake with initially stable, but eventually progressive disease on CT. The other two patients (one with melanoma and one with CRC) showed no significant changes in FLT uptake, whereas CT evaluation showed progressive disease. This is the first report describing changes in FLT-PET in patients receiving Selumetinib. In two patients, changes in FLT uptake as early as after 2 weeks of treatment were consistent with CT results after 8 weeks. Biomarkers to predict and evaluate treatment the outcome of targeted therapies are highly warranted. These initial results need further investigation.


How to cite this article:
Desar IM, Gilles R, van Herpen CM, Timmer-Bonte AN, Cantarini MV, van der Graaf WT, Oyen WJ. 18 F-FLT-PET for response evaluation of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with solid tumors.World J Nucl Med 2012;11:65-69


How to cite this URL:
Desar IM, Gilles R, van Herpen CM, Timmer-Bonte AN, Cantarini MV, van der Graaf WT, Oyen WJ. 18 F-FLT-PET for response evaluation of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with solid tumors. World J Nucl Med [serial online] 2012 [cited 2022 Jan 22 ];11:65-69
Available from: http://www.wjnm.org/article.asp?issn=1450-1147;year=2012;volume=11;issue=2;spage=65;epage=69;aulast=Desar;type=0