Radiosynthesis and biodistribution of 123I-labeled antagonists of the histamine H3 receptor as potential SPECT ligands

Albert D. Windhorst; Henk Timmerman; Rob P. Klok; Franciscus G.J. Custers; Wiro M.P.B. Menge; Rob Leurs; Holger Stark; Walter Schunack; Eric G.J. Gielen; Marinus J.P.G. Van Kroonenburgh; Jacobus D.M. Herscheid

doi:10.1016/S0969-8051(99)00014-1

Radiosynthesis and biodistribution of ¹²³I-labeled antagonists of the histamine H₃ receptor as potential SPECT ligands

Albert D. Windhorst^*, Henk Timmerman, Rob P. Klok, Franciscus G.J. Custers, Wiro M.P.B. Menge, Rob Leurs, Holger Stark, Walter Schunack, Eric G.J. Gielen, Marinus J.P.G. Van Kroonenburgh, Jacobus D.M. Herscheid

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

We have synthesized three ¹²³I-labeled histamine H₃ receptor ligands, i.e., [¹²³I]GR 190028, [¹²³I]FUB 271, and [¹²³I]iodoproxyfan, in moderate to good radiochemical yields via a Cu⁺-assisted I-for-¹²³I exchange method. Biodistribution in the rat of these compounds revealed high hepatic and pulmonary uptake. Brain uptake was moderate, but for [¹²³I]iodoproxyfan, brain uptake was high enough for a pilot single photon emission computed tomography (SPECT) study in the rabbit. However, for this compound, the cerebral uptake could not be blocked by a pretreatment with [R]-α-methylhistamine, a selective, high-affinity histamine H₃ receptor agonist, both in the SPECT study in the rabbit and in the biodistribution study in the rat. Apparently, [¹²³I]iodoproxyfan is binding to a non-H₃ receptor binding site. None of the three investigated compounds is suitable for use as a SPECT ligand for the H₃ receptor in the brain. Copyright (C) 1999 Elsevier Science Inc.

Original language	English
Pages (from-to)	651-659
Number of pages	9
Journal	Nuclear Medicine and Biology
Volume	26
Issue number	6
DOIs	https://doi.org/10.1016/S0969-8051(99)00014-1
Publication status	Published - 1 Aug 1999

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Windhorst, A. D., Timmerman, H., Klok, R. P., Custers, F. G. J., Menge, W. M. P. B., Leurs, R., Stark, H., Schunack, W., Gielen, E. G. J., Van Kroonenburgh, M. J. P. G., & Herscheid, J. D. M. (1999). Radiosynthesis and biodistribution of ¹²³I-labeled antagonists of the histamine H₃ receptor as potential SPECT ligands. Nuclear Medicine and Biology, 26(6), 651-659. https://doi.org/10.1016/S0969-8051(99)00014-1

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title = "Radiosynthesis and biodistribution of 123I-labeled antagonists of the histamine H3 receptor as potential SPECT ligands",

abstract = "We have synthesized three 123I-labeled histamine H3 receptor ligands, i.e., [123I]GR 190028, [123I]FUB 271, and [123I]iodoproxyfan, in moderate to good radiochemical yields via a Cu+-assisted I-for-123I exchange method. Biodistribution in the rat of these compounds revealed high hepatic and pulmonary uptake. Brain uptake was moderate, but for [123I]iodoproxyfan, brain uptake was high enough for a pilot single photon emission computed tomography (SPECT) study in the rabbit. However, for this compound, the cerebral uptake could not be blocked by a pretreatment with [R]-α-methylhistamine, a selective, high-affinity histamine H3 receptor agonist, both in the SPECT study in the rabbit and in the biodistribution study in the rat. Apparently, [123I]iodoproxyfan is binding to a non-H3 receptor binding site. None of the three investigated compounds is suitable for use as a SPECT ligand for the H3 receptor in the brain. Copyright (C) 1999 Elsevier Science Inc.",

keywords = "[I]FUB 271, [I]GR 190028, [I]Iodoproxyfan biodistribution, Histamine H receptor, Single photon emission computed tomography, SPECT, Thioperamide",

author = "Windhorst, {Albert D.} and Henk Timmerman and Klok, {Rob P.} and Custers, {Franciscus G.J.} and Menge, {Wiro M.P.B.} and Rob Leurs and Holger Stark and Walter Schunack and Gielen, {Eric G.J.} and {Van Kroonenburgh}, {Marinus J.P.G.} and Herscheid, {Jacobus D.M.}",

year = "1999",

month = aug,

day = "1",

doi = "10.1016/S0969-8051(99)00014-1",

language = "English",

volume = "26",

pages = "651--659",

journal = "Nuclear Medicine and Biology",

issn = "0969-8051",

publisher = "Elsevier Inc.",

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Windhorst, AD, Timmerman, H, Klok, RP, Custers, FGJ, Menge, WMPB, Leurs, R, Stark, H, Schunack, W, Gielen, EGJ, Van Kroonenburgh, MJPG & Herscheid, JDM 1999, 'Radiosynthesis and biodistribution of ¹²³I-labeled antagonists of the histamine H₃ receptor as potential SPECT ligands', Nuclear Medicine and Biology, vol. 26, no. 6, pp. 651-659. https://doi.org/10.1016/S0969-8051(99)00014-1

TY - JOUR

T1 - Radiosynthesis and biodistribution of 123I-labeled antagonists of the histamine H3 receptor as potential SPECT ligands

AU - Windhorst, Albert D.

AU - Timmerman, Henk

AU - Klok, Rob P.

AU - Custers, Franciscus G.J.

AU - Menge, Wiro M.P.B.

AU - Leurs, Rob

AU - Stark, Holger

AU - Schunack, Walter

AU - Gielen, Eric G.J.

AU - Van Kroonenburgh, Marinus J.P.G.

AU - Herscheid, Jacobus D.M.

PY - 1999/8/1

Y1 - 1999/8/1

N2 - We have synthesized three 123I-labeled histamine H3 receptor ligands, i.e., [123I]GR 190028, [123I]FUB 271, and [123I]iodoproxyfan, in moderate to good radiochemical yields via a Cu+-assisted I-for-123I exchange method. Biodistribution in the rat of these compounds revealed high hepatic and pulmonary uptake. Brain uptake was moderate, but for [123I]iodoproxyfan, brain uptake was high enough for a pilot single photon emission computed tomography (SPECT) study in the rabbit. However, for this compound, the cerebral uptake could not be blocked by a pretreatment with [R]-α-methylhistamine, a selective, high-affinity histamine H3 receptor agonist, both in the SPECT study in the rabbit and in the biodistribution study in the rat. Apparently, [123I]iodoproxyfan is binding to a non-H3 receptor binding site. None of the three investigated compounds is suitable for use as a SPECT ligand for the H3 receptor in the brain. Copyright (C) 1999 Elsevier Science Inc.

AB - We have synthesized three 123I-labeled histamine H3 receptor ligands, i.e., [123I]GR 190028, [123I]FUB 271, and [123I]iodoproxyfan, in moderate to good radiochemical yields via a Cu+-assisted I-for-123I exchange method. Biodistribution in the rat of these compounds revealed high hepatic and pulmonary uptake. Brain uptake was moderate, but for [123I]iodoproxyfan, brain uptake was high enough for a pilot single photon emission computed tomography (SPECT) study in the rabbit. However, for this compound, the cerebral uptake could not be blocked by a pretreatment with [R]-α-methylhistamine, a selective, high-affinity histamine H3 receptor agonist, both in the SPECT study in the rabbit and in the biodistribution study in the rat. Apparently, [123I]iodoproxyfan is binding to a non-H3 receptor binding site. None of the three investigated compounds is suitable for use as a SPECT ligand for the H3 receptor in the brain. Copyright (C) 1999 Elsevier Science Inc.

KW - [I]FUB 271

KW - [I]GR 190028

KW - [I]Iodoproxyfan biodistribution

KW - Histamine H receptor

KW - Single photon emission computed tomography

KW - SPECT

KW - Thioperamide

UR - http://www.scopus.com/inward/record.url?scp=0032590036&partnerID=8YFLogxK

U2 - 10.1016/S0969-8051(99)00014-1

DO - 10.1016/S0969-8051(99)00014-1

M3 - Article

C2 - 10587103

AN - SCOPUS:0032590036

SN - 0969-8051

VL - 26

SP - 651

EP - 659

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

IS - 6

ER -

Radiosynthesis and biodistribution of 123I-labeled antagonists of the histamine H3 receptor as potential SPECT ligands

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Radiosynthesis and biodistribution of ¹²³I-labeled antagonists of the histamine H₃ receptor as potential SPECT ligands