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Evaluation of [ 18 F]2FP3 in pigs and non‐human primates
Author(s) -
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.
Publication year - 2019
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3692
Subject(s) - radioligand , chemistry , in vivo , 5 ht7 receptor , antagonist , receptor , biochemistry , biology , 5 ht receptor , serotonin , microbiology and biotechnology
So far, no suitable 5‐HT 7 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‐HT 7 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‐HT 7 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‐HT 7 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‐HT 7 R antagonists. We speculate that the affinity of the radioligand is too low for imaging the 5‐HT 7 Rs in vivo and that part of the PET signal arises from targets other than the 5‐HT 7 R.