Abstract
A wide repertoire of small molecule PET radiopharmaceuticals has been successfully developed over the last 30–40 years. Both the acceleration of the discovery of novel targets and advances in our understanding of pathophysiological mechanisms have created a rapidly increasing demand for new radiotracers. Alongside the traditional academic pursuit of new radiotracers, the resources of the pharmaceutical industry have been increasingly engaged in creating novel radiotracers for the development of new therapeutics and companion diagnostics. Over the years, rational approaches to the development of radiopharmaceuticals have evolved. This chapter will describe some ‘tried and tested’ approaches that have been used to select, design, and evaluate successful PET radiotracers. The chapter is divided into two parts: ‘design parameters’ and ‘test criteria’. In the first section, we will cover several critical ‘design parameters’ for the creation of effective small molecule radiopharmaceuticals. More specifically, we will discuss an eclectic set of physicochemical and pharmacological properties, guidelines, tolerances, and ‘rules of thumb’ that—when considered together—can assist in the identification of molecules that are more likely to produce successful radiotracers. In the second section, we describe a set of quantitative metrics for a radiolabeled tracer that can be obtained via a series of in vitro and in vivo experiments to determine a radiotracer’s potential utility.
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Chaturvedi S, Mishra AK. Small molecule radiopharmaceuticals – a review of current approaches. Front Med (Lausanne). 2016;3:5.
Kennedy C, Des Rosiers MH, Jehle JW, Reivich M, Sharpe F, Sokoloff L. Mapping of functional neural pathways by autoradiographic survey of local metabolic rate with (14C)deoxyglucose. Science. 1975;187(4179):850–3.
Varrone A, Pappatà S, Quarantelli M. Movement disorders: focus on Parkinson’s disease and related disorders. In: Ciarmiello A, Mansi L, editors. PET-CT and PET-MRI in neurology. Cham: Springer International; 2016. p. 103–25.
Eckelman WC, Reba RC, Gibson RE, Rzeszotarski WJ, Vieras F, Mazaitis JK, et al. Receptor-binding radiotracers: a class of potential radiopharmaceuticals. J Nucl Med. 1979;20(4):350–7.
Patel S, Gibson R. In vivo site-directed radiotracers: a mini-review. Nucl Med Biol. 2008;35(8):805–15.
Waterhouse RN. Determination of lipophilicity and its use as a predictor of blood-brain barrier penetration of molecular imaging agents. Mol Imaging Biol. 2003;5(6):376–89.
Baciu M, Sebai SC, Ces O, Mulet X, Clarke JA, Shearman GC, et al. Degradative transport of cationic amphiphilic drugs across phospholipid bilayers. Philos Trans A Math Phys Eng Sci. 2006;364(1847):2597–614.
Wilson AA, Ginovart N, Schmidt M, Meyer JH, Threlkeld PG, Houle S. Novel radiotracers for imaging the serotonin transporter by positron emission tomography: synthesis, radiosynthesis, and in vitro and ex vivo evaluation of (11)C-labeled 2-(phenylthio)araalkylamines. J Med Chem. 2000;43(16):3103–10.
Wilson AA, Ginovart N, Hussey D, Meyer J, Houle S. In vitro and in vivo characterisation of [11C]-DASB: a probe for in vivo measurements of the serotonin transporter by positron emission tomography. Nucl Med Biol. 2002;29(5):509–15.
Houle S, Ginovart N, Hussey D, Meyer JH, Wilson AA. Imaging the serotonin transporter with positron emission tomography: initial human studies with [11C]DAPP and [11C]DASB. Eur J Nucl Med. 2000;27(11):1719–22.
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Gee, A.D., Bongarzone, S., Wilson, A.A. (2019). Small Molecules as Radiopharmaceutical Vectors. In: Lewis, J., Windhorst, A., Zeglis, B. (eds) Radiopharmaceutical Chemistry. Springer, Cham. https://doi.org/10.1007/978-3-319-98947-1_7
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DOI: https://doi.org/10.1007/978-3-319-98947-1_7
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