Evaluation of [18F]2FP3 in pigs and non-human primates
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Evaluation of [18F]2FP3 in pigs and non-human primates. / Hansen, Hanne D.; Constantinescu, Cristian C; Barret, Olivier; Herth, Matthias M.; Magnussen, Janus H; Lehel, Szabolcs; Dyssegaard, Agnete; Colomb, Julie; Billard, Thierry; Zimmer, Luc; Tamagnan, Gilles; Knudsen, Gitte M.
In: Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 62, No. 1, 2019, p. 34-42.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Evaluation of [18F]2FP3 in pigs and non-human primates
AU - Hansen, Hanne D.
AU - Constantinescu, Cristian C
AU - Barret, Olivier
AU - Herth, Matthias M.
AU - Magnussen, Janus H
AU - Lehel, Szabolcs
AU - Dyssegaard, Agnete
AU - Colomb, Julie
AU - Billard, Thierry
AU - Zimmer, Luc
AU - Tamagnan, Gilles
AU - Knudsen, Gitte M.
PY - 2019
Y1 - 2019
N2 - So far, no suitable 5-HT7 R radioligand exists for clinical positron emission tomography (PET) imaging. [18 F]2FP3 was first tested in vivo in cats, and the results were promising for further evaluations. Here, we evaluate the radioligand in pigs and non-human primates (NHPs). Furthermore, we investigate species differences in 5-HT7 R binding with [3 H]SB-269970 autoradiography in post-mortem pig, NHP, and human brain tissue. Specific binding of [18 F]2FP3 was investigated by intravenous administration of the 5-HT7 R specific antagonist SB-269970. [3 H]SB-269970 autoradiography was performed as previously described. [18 F]2FP3 was synthesized in an overall yield of 35% to 45%. High brain uptake of the tracer was found in both pigs and NHPs; however, pretreatment with SB-269970 only resulted in decreased binding of 20% in the thalamus, a 5-HT7 R-rich region. Autoradiography on post-mortem pig, NHP, and human tissues revealed that specific binding of [3 H]SB-269970 was comparable in the thalamus of pig and NHP. Despite the high uptake of [18 F]2FP3 in both species, the binding could only be blocked to a limited degree with the 5-HT7 R antagonists. We speculate that the affinity of the radioligand is too low for imaging the 5-HT7 Rs in vivo and that part of the PET signal arises from targets other than the 5-HT7 R.
AB - So far, no suitable 5-HT7 R radioligand exists for clinical positron emission tomography (PET) imaging. [18 F]2FP3 was first tested in vivo in cats, and the results were promising for further evaluations. Here, we evaluate the radioligand in pigs and non-human primates (NHPs). Furthermore, we investigate species differences in 5-HT7 R binding with [3 H]SB-269970 autoradiography in post-mortem pig, NHP, and human brain tissue. Specific binding of [18 F]2FP3 was investigated by intravenous administration of the 5-HT7 R specific antagonist SB-269970. [3 H]SB-269970 autoradiography was performed as previously described. [18 F]2FP3 was synthesized in an overall yield of 35% to 45%. High brain uptake of the tracer was found in both pigs and NHPs; however, pretreatment with SB-269970 only resulted in decreased binding of 20% in the thalamus, a 5-HT7 R-rich region. Autoradiography on post-mortem pig, NHP, and human tissues revealed that specific binding of [3 H]SB-269970 was comparable in the thalamus of pig and NHP. Despite the high uptake of [18 F]2FP3 in both species, the binding could only be blocked to a limited degree with the 5-HT7 R antagonists. We speculate that the affinity of the radioligand is too low for imaging the 5-HT7 Rs in vivo and that part of the PET signal arises from targets other than the 5-HT7 R.
U2 - 10.1002/jlcr.3692
DO - 10.1002/jlcr.3692
M3 - Journal article
C2 - 30414212
VL - 62
SP - 34
EP - 42
JO - Journal of Labelled Compounds and Radiopharmaceuticals
JF - Journal of Labelled Compounds and Radiopharmaceuticals
SN - 0362-4803
IS - 1
ER -
ID: 209931730