Reply: Measurement of regional rates of protein synthesis in human brain in vivo with L-[1-¹¹C]-leucine PET

Sir,

We are pleased that researchers in the field of brain metabolism have taken notice of our work (Smith and Schmidt, 2018). As described in our introduction, we acknowledge the work using atmospheric tracer incorporation (Libby et al., 1964) as well as the L-[1-¹¹C]-leucine PET method (Hawkins et al., 1989; Sundaram et al., 2006) to estimate brain protein synthesis rates. Though the latter method has been further developed by Dr Smith and Ms Schmidt and validated against autoradiographic methods in rhesus monkeys (Schmidt et al., 2005; Smith et al., 2005), no studies have directly assessed incorporation of labelled amino acids in brain tissue protein in vivo in humans. In our study we applied contemporary stable isotope methodology with continuous tracer infusion and blood and tissue sampling to directly assess fractional brain protein synthesis rates in vivo in humans (Smeets et al., 2018). The main limitation of this direct method is indeed the need for tissue sampling. As such, non-invasive methods as referred to by Dr Smith and Ms Schmidt will be required to elucidate many aspects of brain protein synthesis rates in both health and disease.

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