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Concerning the Distribution of Cerebral Muscarinic Acetylcholine Receptors in Alzheimer's Disease-Reply

Daniel R. Weinberger, MD; Douglas W. Jones, PhD; Richard Coppola, DSc; Karen Faith Berman, MD; Raymond Gibson, PhD; Richard C. Reba, MD
Arch Neurol. 1991;48(11):1118-1118. doi:10.1001/archneur.1991.00530230025012
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In Reply.  —In his letter, Zeeberg questions whether the radioiodinated 3-quinuclidinyl-4-iodobenzilate (IQNB) single photon emission computed tomographic (SPECT) images in normal subjects and in patients with dementia described in our article1 reflect primarily muscarinic receptor binding or regional cerebral blood flow (rCBF). We discussed this issue extensively in our article and spoke directly and repeatedly to the concern raised in this letter. Nevertheless, the author of this letter ignores most of our discussion and most of the in vivo data about IQNB, choosing instead to challenge a "straw man" of his own construction. He focuses on our observation regarding the cerebellum and uses this to build his case for an rCBF phenomenon. The cerebellum observation, as clearly discussed in our article, served only to demonstrate that the SPECT images at prolonged times after IQNB administration were distinctly different from, and in marked contrast to, rCBF images, and they indicated

REFERENCES

Weinberger DR, Gibson R, Coppola R, et al.  The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia: a controlled study with 123-IQNB and SPECT . Arch Neurol . 1991;;48:169-176.
Weinberger DR, Mann U, Gibson RE, et al.  Cerebral muscarinic receptors in primary degenerative dementia as evaluated by SPE CT with iodine123-labeled QNB . In: Wurtman RJ, Corkin S, Growdon JH, Ritter E, eds. Advances in Neurology: Alzheimer's Disease . New York, NY: Raven Press; 1990;;51:147-150.
Weinberger DR, Mann U, Reba RC, et al.  Comparison of 18FDG PET and 23I-QNB SPECT in patients with dementia . J Nucl Med . 1989;;30:896.
Jones DW, Saunders RC, Gorey JG, et al.  Dynamic SPECT comparison of I-123-QNB kinetics and blood flow (Tc-99m-ECD) in monkey . J Nucl Med . 1990;;31:707.
Sawada Y, Hiraga S, Francis B, et al.  Kinetic analysis of 3-quinuclidinyl 4-[125I]iodobenzilate transport and specific binding to muscarinic acetylcholine receptor in rat brain in vivo: implications for human studies . J Cereb Blood Flow Metab . 1990;;0:781-807.
Zeeberg BR, Reid RC, Murphy KA, Reba RC.  Theoretical effects of radioligand diffusional gradients and microscopic neuroreceptor distribution in in vivo kinetic studies . Bull Math Biol . 1988;;50:423-444.

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Weinberger DR, Gibson R, Coppola R, et al.  The distribution of cerebral muscarinic acetylcholine receptors in vivo in patients with dementia: a controlled study with 123-IQNB and SPECT . Arch Neurol . 1991;;48:169-176.
Weinberger DR, Mann U, Gibson RE, et al.  Cerebral muscarinic receptors in primary degenerative dementia as evaluated by SPE CT with iodine123-labeled QNB . In: Wurtman RJ, Corkin S, Growdon JH, Ritter E, eds. Advances in Neurology: Alzheimer's Disease . New York, NY: Raven Press; 1990;;51:147-150.
Weinberger DR, Mann U, Reba RC, et al.  Comparison of 18FDG PET and 23I-QNB SPECT in patients with dementia . J Nucl Med . 1989;;30:896.
Jones DW, Saunders RC, Gorey JG, et al.  Dynamic SPECT comparison of I-123-QNB kinetics and blood flow (Tc-99m-ECD) in monkey . J Nucl Med . 1990;;31:707.
Sawada Y, Hiraga S, Francis B, et al.  Kinetic analysis of 3-quinuclidinyl 4-[125I]iodobenzilate transport and specific binding to muscarinic acetylcholine receptor in rat brain in vivo: implications for human studies . J Cereb Blood Flow Metab . 1990;;0:781-807.
Zeeberg BR, Reid RC, Murphy KA, Reba RC.  Theoretical effects of radioligand diffusional gradients and microscopic neuroreceptor distribution in in vivo kinetic studies . Bull Math Biol . 1988;;50:423-444.

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