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. 2018 Nov 18;39(3):1014–1052. doi: 10.1002/med.21552

Table 1.

Agonist tracers developed for the imaging of high‐affinity state of neuroreceptors

Receptors Tracer names In vitro evaluation In vivo evaluation Remarks
Agonism proven by a , b Preference for Rhigh proven by c Rodents Non‐human primates Other animals Humans Sensitive to endogenous neurotransmitter levels d
Dopamine D1/5 (S)(+)[11C]SKF82957 ND COMP+ GTPdis+76 Rats77, 78, 79 ND ND ND Rats–77 Lipophilic metabolites in brain tissue
(S)[11C]NNC 01‐0259 MESS+80 ND ND 81, 82, 83 ND ND Primates–80 Lipophilic metabolites in brain tissue
Dopamine D2/3 [11C]PHNO ND GTPdis+84 COMP+85 SAT−86 Rats72, 87, 88 89 Cats90 91 (first) Rats+72, 87, 88 cats+90 primates+92 humans+93, 94 Now primarily used as D3‐selective tracer95 derivation of 18F‐version unsuccessful96
[11C]NPA ND COMP+56, 85 Rats97 97, 98, 99 Cats90 pigs100 101 (first) Cats+90 primates+99 humans+102 Relatively difficult radiosynthesis
[11C]MNPA ND COMP+28 SAT−86 Mice44, 103 rats104 105, 106, 107, 108, 109, 110 ND 111 (first) Rats+104 mice+44 primates+109 Lowest BPND (see Section 5.1.1) among D2/3 tracers used in humans
[18F]MCL‐524 ND COMP+112 ND 113 ND ND Primates+113 Structurally related to NPA and MNPA
Dopamine D2 [11C]SV‐III‐130 MESS+114 ND ND 114 ND ND Primates+114 Possible 5‐HT1A binding
Dopamine D3 [18F]LS‐3‐134 MESS+115 COMP−116 ND 115 ND ND Primates+115 Specific binding seen only after dopamine depletion
[18F]7‐OH‐FHXPAT ND GTPdis+117 mice, rats117 ND ND ND ND D3‐over‐D2 selectivity not fully characterized
Serotonin 5‐HT1A [11C]CUMI‐101 GTPrec– 118 GTPrec±119 ND ND 70, 120 ND 71, 121 Rodents−122 primates+123 humans−124 humans±125 Variable intrinsic activity 118, 119, 126 binds to adrenoceptors118, 126 derivation of 18F‐version successful127, 128
[18F]F13714 GTPrec+ MESS+129 GTPdis+130 Rats130 131 Cats130 marmosets132 ND ND Specific binding is irreversible
[18F]F13640 GTPrec+133 ND Rats134 134 Cats134 ND Rats+134 Slow, but reversible binding kinetics
Serotonin 5‐HT2A [11C]CIMBI‐36 MESS+135 ND Rats, mice (only safety)136 137 Pigs135 138, 139, 140 Pigs+141 primates+142 humans−143 Also binds to 5‐HT2C 137 alternative 11C‐labeling positions compared 140 derivation of 18F‐version unsuccessful144
κ‐Opioid [11C]GR103545 also known as (R)‐[11C]GR89696 PHYS+ (for κ) COMP±145 Mice146 (race‐mate)147 (eutomer) 68, 69, 148 ND 149, 150 ND Competition assay shows biphasic binding but this may reflect different affinities for κ
µ‐Opioid [11C]carfentanil (mu‐OR) PHYS+151 ND Mice152 rats43 153 ND 153(first) Rats+43 humans+154, 155, 156 humans−157 Derivation of 18F‐version successful, no follow‐up158
µ/κ‐Opioid [11C]PEO GTPrec+159 ND Rats159 ND ND ND ND Derivation of 18F‐version successful160, 161
Muscarinic M1 [11C]LSN3172176 GTPrec+162 COMP−162 163, 164 ND Imperfect subtype‐selectivity
[11C]AF‐150(S) ND COMP+20 Rats165, 166 ND ND ND Rats±166 Low signal‐to‐noise ratios
Muscarinic M2 [18F]FP‐TZTP PHYS+167 ND Mice168 rats 169, 170, 171 170 ND 172(first) Primates+173 11C‐version created, no follow‐up174

Abbreviations GDP, guanosine diphosphate; GTP, guanosine triphosphate; ND, no data available.

a

Coding of experimental paradigms aiming to confirm agonism: MESS monitoring secondary messenger levels in functional assays in vitro; GTPrec monitoring GTP recruitment to G‐proteins in vitro; PHYS monitoring physiological or behavioral effects of the compound in vivo or ex vivo.

b

Works confirming functional agonism are cited only if the preference for Rhigh has not been directly confirmed.

c

Coding of experimental paradigms aiming to confirm preferential binding to Rhigh: COMP obtaining a biphasic competition curve in vitro; SAT obtaining a biphasic saturation curve in vitro; GTPdis detecting the loss of specific binding upon GTP or GppNHp addition in vitro.

d

Coding of the outcomes of studies confirming sensitivity to endogenous neurotransmitter levels (and also agonism and Rhigh preference): +, positive outcome; −, negative outcome, ±, ambiguous results.