123I‐IOMAZENIL AS A CLINICAL TOOL FOR STUDYING NEURONAL LOSSписьмо
Аннотация: To the Editor: We want to draw attention to the potential clinical usefulness of 123I-Iomazenil1 in older subjects. Similar to its close relative flumazenil, this benzodiazepine is an antagonist of the benzodiazepine-binding site on the postsynaptic GABAA receptor of the inhibitory synapses, a receptor probably present on all neurons. So far, the study of 123I-Iomazenil and 11C-flumazenil to develop a technique for quantitation of receptors has used primarily sophisticated compartmental models. The success of this endeavor is based on the well known fact that ligands are specific inasmuch as they do not bind to other receptors in the brain; moreover, the determination of receptor density {Bmax/affinity (Kd)} — as shown in vivo — gives practicallythe same values as found by simple in vitro studies on cortex homogenates.2, 3 Two simple quantitation methods have been developed: (1) the bolus tracer injection table-look-up procedure, based on two or more images, and (2) the constant infusion method, where only a single image taken at steady state is needed for quantitation. For both methods, a single venous blood sample suffices to measure the free tracer concentration with which the brain equilibrates. It is now possible to use this tool clinically to perform parametric imaging, i.e., quantifying scans in terms of the binding potential (Bmax/Kd), which is practically the same as mapping Bmax — the benzodiazepine receptor concentration — since Kd can be considered constant.2, 3 This mode of expressing the background of 123I-Iomazenil SPECT imaging may sound obscure and may confuse nonspecialists in nuclear medicine or neurology. The primary questions are: what does one measure, and what do we need it for? Our letter aims to answer these two questions. As to the first, 123I-Iomazenil gives a measure of the concentration of the most important synapses of the brain — the inhibitory synapses — which are all GABA-ergic, i.e., they use gamma amino butyric acid as transmitter. The answer to the second question — what is it good for? — is the clinically important one. Here it can be argued that by measuring the numerous inhibitory synapses, one apparently obtains a measure of all synapses. This allows a quantitative assessment of the integrity of all neurons collectively, which is particularly valid for the cortex, where benzodiazepine receptor concentration is the highest. In essence, current data suggest that it is possible to count indirectly the number of intact neurons in vivo. The potential usefulness of this technique is well known.2, 3 Here we indicate the use of this technique to assess brain cortex damage in neurodegenerative diseases, Alzheimer's disease in particular4 (Figure 1). In such states 123I-Iomazenil gives quantitative information similar to that obtained by 99mTC-HMPAO, but Iomazenil images are not influenced by tissue blood flow. These images show only one parameter, for instance the receptors in stroke. 123I-Iomazenil provides a better image of selective neuronal loss (incomplete infarction, invisible on CT or MRI) than does 99 mTC-HMPAO, which is also influenced by confounding factors such as reduced flow or disconnection. The use of 123I-Iomazenil SPECT would enable broader exploration in the field of neurological diseases as this unique tracer has a brain uptake of about 12% of the injected dose. This is higher than that of any other tracer and thus allowis good imaging to be carried out with the use of little radioactive compound. SPECT images, obtained with a brain-dedicated device (CERASPECT, Digital Scintigraphics Inc. MA), in a 64-year-old man with moderate Alzheimer's disease (probable AD, according to the criteria of NINCDS/ADRDA). Image level is 6.5 cm above the level of external ear channel. 99 mTC-HMPAO shows bilateral but predominantly left-sided blood flow reduction of the temporo-parietal lateral region, posteriorly. On the anterior left side there is also a suggestion of flow reduction With 123I-Iomazenil, the same changes are seen, but in a clearer manner, pointing to massive loss of GABAA synapses in both hemispheres but mainly on the left side.
Год издания: 1997
Издательство: Wiley
Источник: Journal of the American Geriatrics Society
Ключевые слова: Anesthesia and Sedative Agents
Другие ссылки: Journal of the American Geriatrics Society (PDF)
Journal of the American Geriatrics Society (HTML)
PubMed (HTML)
Journal of the American Geriatrics Society (HTML)
PubMed (HTML)
Открытый доступ: bronze
Том: 45
Выпуск: 4
Страницы: 534–536