Membrane transporters in PET imaging

Cellular membranes form a barrier to most of organic and inorganic solutes. Specific transporter proteins enable strictly regulated transport of solutes across the membranes, down or against their concentration gradient. Transport against the concentration gradient (“active” transport) requires energy, which is obtained by exploiting ion gradients or from subsequent ATP turnover. For reviews on transporters, see the references. In the absence of transporter, membrane permeability is correlated with the solutes oil/water partition coefficient. Lipid bilayer membranes are heterogeneous, with higher lipophilicity in the centre of the bilayer, which is taken into account in inhomogeneous solubility-diffusion model.

PET tracers are being used and actively developed for studying the function and localization of transporters. Transporters are not only important as targets of functional PET imaging, but transporters indirectly affect the usability of PET tracers for studying other functions, since transporters are needed for the tracer to reach their targets across epithelial barriers (such as BBB) and in intracellular organelles. Transporters are also involved in the excretion of PET tracers from the body, and the distribution of their radioactive metabolites.

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Alexander SP, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA, CGTP Collaborators. The Concise Guide to PHARMACOLOGY 2015/16: Transporters. Br J Pharmacol. 2015; 172(24): 6110-6202. doi: 10.1111/bph.13355.

Endres CJ, Hsiao P, Chung FS, Unadkat JD. The role of transporters in drug interactions. Eur J Pharm Sci. 2006; 27: 501-517.

Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, Chu X, Dahlin A, Evers R, Fischer V, Hillgren KM, Hoffmaster KA, Ishikawa T, Keppler D, Kim RB, Lee CA, Niemi M, Polli JW, Sugiyama Y, Swaan PW, Ware JA, Wright SH, Yee SW, Zamek-Gliszczynski MJ, Zhang L. Membrane transporters in drug development. Nat Rev Drug Discov. 2010; 9(3): 215-236.

Kilbourn MR. Small molecule PET tracers for transporter imaging. Semin Nucl Med. 2017; 47(5): 536-552. doi: 10.1053/j.semnuclmed.2017.05.005.

Mann A, Semenenko I, Meir M, Eyal S. Molecular imaging of membrane transporters’ activity in cancer: a picture is worth a thousand tubes. AAPS J. 2015; 17(4): 788-801.

Nakanishi T. Drug transporters as targets for cancer chemotherapy. Cancer Genomics Proteomics 2007; 4(3): 241-254.

Shinoda W. Permeability across lipid membranes. Biochim Biophys Acta 2016; 1858: 2254-2265. doi: 10.1016/j.bbamem.2016.03.032.

Shitara Y, Horie T, Sugiyama Y. Transporters as a determinant of drug clearance and tissue distribution. Eur J Pharm Sci. 2006; 27(5): 425-446.

Steffansen B, Brodin B, Nielsen CU (eds.): Molecular Biopharmaceutics. Pharmaceutical Press, 2010, ISBN: 978-0-85369-722-0.

Wulkersdorfer B, Wanek T, Bauer M, Zeitlinger M, Müller M, Langer O. Using positron emission tomography to study transporter-mediated drug-drug interactions in tissues. Clin Pharmacol Ther. 2014; 96(2): 206-213.

Xu H, Martinoia E, Szabo I. Organellar channels and transporters. Cell Calcium 2015; 58(1): 1-10. doi: 10.1016/j.ceca.2015.02.006.

You G, Morris ME (eds.): Drug Transporters - Molecular Characterization and Role in Drug Disposition, 2nd ed. Wiley, 2014, ISBN: 978-1-118-48993-2.


Updated at: 2018-04-10
Created at: 2015-08-17
Written by: Vesa Oikonen