Table 1 Binding characteristics of selected first- and second-generation tau tracers in in vitro studies

From: Tau PET imaging in neurodegenerative tauopathies—still a challenge

  

Ki/IC50

Kd

Bmax

On-target

Off-target

First-generation tau PET tracers

PBB3

Ki1: 1.3; 5.9 Ki2: 23.5

Ki1:2.5; Kd2:100

Bmax1: 25 nM; Bmax2: 300 nM

NFTs, neuropil threads, neuritic plaques; pick bodies, tau inclusion in PiD, PSP, CBD

Dense core amyloid plaques; diffuse amyloid-β- deposits, astrocytic plaques

AV1451

Ki1: 0.3; 3.3 Ki2: 97.2

0.63–3.72; 15/14.6

15–119.7

PHFs tau, pretangles, mature tangles, neuritic and primitive plaques (to a limited extent)

Dense core amyloid-β plaques; melanin containing structure, lipofuscin containing structures, mineralized structures, MAO-A, MAO-B

THK5117

Ki1: 0.001; 0.0005 Ki2: 10.5–27.4 Ki3: 750-800

Kd1: 2.2–3.1; Kd2: 23.6–34.6/Kd: 5.19–11.5/5.2

Bmax1: 250 Bmax2: 1226–1416; 338

Pretangles, PHF tau, NFsT, neuritic plaques, argyrophillic grains, argyrophilic threads, globose tangles

MAO-B

THK5351

Ki1: 0.1 pM Ki2: 16

2.9 mol/l; Kd1: 5.6; Kd2: 1

368; Bmax1: 76, Bmax2: 40

NFTs, thread like structures in white matter, tufted astrocytes

MAO-B

Second-generation tau PET tracers

MK-6240

Ki:0.36

0.14–0.38

7–93.4 nM

NFTs

No off-target binding to MAO-A, MAO-B

RO-948

IC50: 18.5

 

9.7

NFTs, neuropil threads

Extensive screening shows no off-target binding

RO1643

IC50: 10

 

5.5

NFTs, neuropil threads

Extensive screening shows no off-target binding

RO4693

IC50: 5.5

 

5.9

NFTs, neuropil threads

Extensive screening shows no off-target binding

PI-2620

IC50: 1.8

  

3R tau from Pick, 4R from PSP

No off-target binding to MAO-A, MAO-B

JNJ311

Ki = 8

  

PHF tau, neuritic plaques

 

JNJ-067

 

2.4

 

NFTs

No off-target binding to MAO-A, MAO-B

GTP1

 

14.9 ± 4.3

  

No off-target binding to MAO-A, MAO-B

PM-PBB3

 

<10

 

Tau aggregates in AD and PSP

 

AM-PBB3

 

<10

 

Tau aggregates in AD and PSP

No off-target binding in basal ganglia and thalamus

References

 

[30,32,33, 123, 149, 152, 239,240,241,242]

[25, 26, 32, 34, 123, 142, 149, 152, 239, 240, 243,244,245]

[25, 26, 32, 123, 142, 149, 152, 239, 241]

[26, 30,32,33,34, 78, 111, 112, 118, 142, 149, 150, 152, 239, 241, 242, 244,245,246,247]

[26, 32, 33, 111, 112, 123, 146, 149, 241, 242, 245, 247]

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