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Transport of 99mTc-MAG3 via rat renal organic anion.

The terms molecular imagingand molecular biologyare being used increasingly in modern medicine. This reflects not so much a change in what we do as it does a refinement in our understanding and the conceptual approach to what we do. This advancement is not restricted to medicine but pervades our daily life. Our ability to achieve finer and finer detail is reflected in a wide range of devices, from the computers we use in our daily work, which have become smaller, faster, and more powerful, to those things that occupy our leisure time. Turning on a high-fidelity set at home provides us with increasingly accurate reproduction of sound as it was originally generated, through improving technology and our ability to reproduce smaller and smaller bits of the original. The report by Shikano et al. (1) in this issue of The Journal of Nuclear Medicinedescribes a study using the organic anion transporter 1 (OAT1) in Xenopus laevis oocytes. This model of the isolated transporter made it possible for the investigators to study 99mTc-mercaptoacetylglycylglycylglycine (MAG3) transport by OAT1 and the in vitro inhibition of its uptake by p-aminohippuric acid (PAH), hippuran (OIH), probenecid, and other compounds. These data help us to understand in greater clarity how the kidney handles 99mTc-MAG3. It is possible to obtain similar information without isolation of the transporter, but the experiments are much more complicated and expensive since they usually have to be performed in vivo and the results are not as specific. The classic text by Homer Smith, The Kidney: Structure and Function in Health and Disease(2), reviews many experiments on intact organisms and humans. Although the words transport, receptor, and anion do not appear in the index, hippurandoes. In a section on competition in tubular transport (page 202), Professor Smith reports on how competition between a variety of substances affects their net excretion. He notes that the authors of these studies interpreted their results in terms of “competition for available energy.” Early on it was recognized that energy was expended to move PAH into the cell and then into the urine. The concept that there were specific molecules (transporters) to achieve these actions was an abstract thought at that time. Throughout the subsequent years, numerous studies have been done on intact animals and sometimes on humans in which compounds have been infused simultaneously to determine their interaction. In some situations, the effect of an agent on renal function was measured using a standard of measurement such as PAH without any means of identifying whether the infused agent was affecting renal function per se or was affecting the transport of PAH. So, too, has it been difficult to differentiate the relative effects of renal transport and reabsorption and, except in a relatively crude manner, to identity the portion of the renal tubule involved in the excretion of a compound. This lack of refinement has sometimes fueled controversy over how a particular compound is handled by the kidney and, more important, over the significance of changes in its excretion. The isolation and measurement of transport of compounds and competition for transport by specific kidney transporters in in vitro models of the type used in this study serve several important functions. First, they help us to better understand how a specific compound is excreted and, therefore, what it is we are measuring when we use that compound in studying the kidney. Also, and perhaps equally or more important, by having the transporter available to us it is possible to prospectively construct compounds that are more ideally suited to transport by that molecule and, therefore, that can potentially provide us with more specific and useful information about the component of kidney function in question. The story of how we arrived at the state of knowledge that made the subject of this commentary possible is an educational and instructive lesson. Early studies as noted previously were done on intact organisms or in some cases on kidney slices or kidneys that had been excised from an animal and were perfused in vitro. In an article on renal tubular transport, Cross and Taggart (3) stated that “investigations on the biochemical mechanisms involved in active renal transport are difficult to approach with the various experimental techniques now available.” The step forward at that time, which was reported in that study, was the use of rabbit kidney slices contained in a Warburg apparatus. The authors were able to show that slices of rabbit kidney cortex could accumulate PAH against a concentration gradient. They also showed the stimulatory effect of acetate on PAH transport. Subsequently, innumerable studies of PAH transport were performed on a wide variety of biologic models. Moller and Sheikh (4) reviewed the Received Sep. 22, 2003; revision accepted Oct. 3, 2003. For correspondence or reprints contact: M. Donald Blaufox, MD, PhD, Nuclear Medicine, Montefiore Medical Park, Albert Einstein College of Medicine, 1695A Eastchester Rd., Bronx, NY 10461. E-mail: blaufox@aecom.yu.edu