Imaging of dopamine transporters in humans with technetium-99m TRODAT-1

We have read the recent manuscript of Dr. Hank Kung and co-workers, published in the November 1996 issue of the European Journal of Nuclear Medicine [1], and would like to comment on this short communication. Dr. Kung reports on a technetium-99m labeled tropane which images the dopamine transporter: "In this paper, the first human imaging study of dopamine transporters using a 99mTc-labeled tropane derivative is described." Unfortunately, in this manuscript Dr. Kung displays a surprising lack of familiarity with progress in the field of 99mTe imaging of the dopamine transporter. Although his is the first study to be conducted in humans, it is not the first report of a 99mTc-labeled compound which provides SPET imaging targeted to the dopamine transporter in primate brain. In 1994, we submitted a fully documented grant proposal to the Department of Health and Human Services in which we described the design and proposed synthesis of the first 99mTc-labeled agents to target the dopamine transporter. This grant application was peer-reviewed and funded. We subsequently prepared a 99mTc-labeled compound, thefirst to target the dopamine transporter in primate brain. It yielded SPET images in primate brain consistent with labeling of the dopamine transporter. Our first report with a successful SPET image in primate brain was published in March 1996 [2], at least 3 months before Dr. Kung's submission to Eur J Nucl Med (submission date: June 10, 1996; publication date: November 1996). Dr. Kung's current paper makes no reference to it. Meegella, Kung et al. published a brief note regarding the synthesis of a 99mTc-labeled tropane [3] and reported the failure of this compound to provide useful images in primate brain [1, 4]: "... the agent did not provide good contrast in the basal ganglia area in SPET images in nonhuman primates (unpublished data)." In June 1996 our SPET imaging study was reported at the annual meeting of the Society for Nuclear Medicine in the same session in which Dr. Kung reported his findings, and the abstract, published in the Society for Nuclear Medicine journal, was available at that time. The Kung manuscript does not refer to the prior and first publication of a 99mTc agent which targets the dopamine transporter and provides SPET images in primates. In fact, his description of the etiology of these brain imaging agents is rather incomplete. Our published manuscript [2] reported: "... the 99m technetium-labeled analogue is the first reported compound to cross the bloodbrain barrier and accumulate in a selective target, the striatum. The brain entry of technepine was particularly exciting, as several attempts at developing technetiumlabeled probes for specific targets in brain have not been successful." Our technetium labeled dopamine transport ligand will not be administered to human subjects until safety, toxicity, and other important issues meet with our own stringent standards and the approval of the Food and Drug Administration of the USA, our governing body. It would be useful for the field if the authors included information regarding approval by an oversight board in Seoul, Korea, where the study was conducted, concerning the safety and toxicity of their imaging agent for a first human experiment.