Dataset Open Access

Data publication: Enantioselective Synthesis, Structure Activity Relationship, Radiofluorination and Biological Evaluation of [18F]RM365, a Novel Radioligand for Imaging the Human Cannabinoid Receptor Type 2 (CB2R) in the Brain with PET

Teodoro, Rodrigo; Gündel, Daniel; Deuther-Conrad, Winnie; Toussaint, Magali; Wenzel, Barbara; Bormans, Guy; Kopka, Klaus; Brust, Peter; Moldovan, Rares-Petru

The development of cannabinoid receptor type 2 (CB2R) PET radioligands has been intensively explored due to the pronounced CB2R upregulation in various pathological conditions, such as neuroinflammation and cancer. Herein we report on the enantioselective synthesis of a series of highly affine fluorinated indole-2-carboxamide ligands targeting the CB2R in the brain. Compound RM365 was selected for PET radiotracer development due to its high CB2R affinity (Ki = 2.1 nM) and pronounced selectivity over CB1R (factor > 300). A fully automated copper-mediated radiofluorination of [18F]RM365 was established starting from the corresponding aryl boronic acid pinacol ester precursor. Preliminary in vitro evaluation of [18F]RM365 indicated species differences in the binding to CB2R (KD of 2.32 nM for the human CB2R vs. KD > 10000 nM for the rat CB2R). Metabolism studies in mice revealed high stability of [18F]RM365 with fractions of parent compound of > 90% in the brain and > 54% in the plasma at 30 min p.i. PET imaging in a rat model of local hCB2R(D80N) overexpression in the brain demonstrate the ability of [18F]RM365 to reach and selectively label the intracranial expressed hCB2R(D80N) with high signal-to-background ratio. Thus, [18F]RM365 is a very promising PET radioligand for the imaging of upregulated hCB2R expression under pathological conditions with high potential towards clinical application in humans.

Files (21.3 MB)
Name Size
Anlage 2-NMR-Formular.doc
md5:9a2625e7a155555d3ff7c8a3e53eb18c
111.6 kB Download
RM 350B1.10.fid.zip
md5:9f6d3856362b43b78e881a959403d9d6
174.5 kB Download
RM 350B2.10.fid.zip
md5:34269f36608daa4233ff4b1ca344d3b0
172.1 kB Download
RM 390-1.10.fid.zip
md5:c7cfec9729afc9ab7cf1f11818d9cf21
178.9 kB Download
RM 390-2.10.fid.zip
md5:743eb19e988c33a45e44e760afb0fee0
178.7 kB Download
RM 391-1.10.fid.zip
md5:f9f700c5e9e342012ecfcd6617ed6137
178.4 kB Download
RM 391-2.10.fid.zip
md5:e1f832900b3177d4c22525fd919afff0
168.6 kB Download
RM188.10.fid.zip
md5:b0ac3e7944278af1495c6a7d01416b30
156.4 kB Download
RM259F3_PROTON_01.fid.tar
md5:5c578a465420e8db2e8ba9c09da6fab6
174.1 kB Download
RM343A.10.fid.zip
md5:3d94fcca371ade144a2e1ca493e71321
160.7 kB Download
RM343B.10.fid.zip
md5:bf94bf98561fb02f622355abb519414d
154.8 kB Download
RM343C.10.fid.zip
md5:85dd63ca250588b62899a0995eed67a7
160.5 kB Download
RM346.10.fid.zip
md5:c67084898dfd6506291b8155c656f296
162.4 kB Download
RM350_1_PROTON_01.fid.tar
md5:eecb09c5a160eeaaa5eebb399843ca26
174.1 kB Download
RM351.10.fid.zip
md5:c3b8a48700f8b41267b22bd71b2bd701
161.9 kB Download
RM351.11.fid.zip
md5:e101d6a28ad881b349743995e6d6c3d3
228.4 kB Download
RM351_.10.fid.zip
md5:a21f9072e7a6b7d7e20fca9e150bd1a7
167.9 kB Download
RM352.10.fid.zip
md5:0f525d9a35e1e4e09a2e5ef16c2d6ac8
166.3 kB Download
RM354.10.fid.zip
md5:9ac1d3d3a94f62cb0fd4c091184a09ae
151.2 kB Download
RM356_1.10.fid.zip
md5:bced4b8675b41371501c858530905f1a
164.5 kB Download
RM356_2.10.fid.zip
md5:6ceaa98016ed470ffb75e60c3b5bd8cd
168.7 kB Download
RM360F1.10.fid.zip
md5:f70ac834e145e77d76ea780de7b536ee
168.5 kB Download
RM360F1.11.fid.zip
md5:838a589c5a9ddea3786cc4d519c4775f
217.6 kB Download
RM360F2.10.fid.zip
md5:961f8a67167cc99131cb8569e975a945
167.9 kB Download
RM360F2.11.fid.zip
md5:d76619902935bcb8d96828581f5678e8
218.7 kB Download
RM365FO_PROTON_01.fid.tar
md5:36ffe85fc098bbb9164751870cab95fa
174.1 kB Download
RM366.10.fid.zip
md5:fa7c9f6a516641262c91e1f480396036
166.8 kB Download
RM366.11.fid.zip
md5:d55e3f46987459357a1515254fbe94b2
220.5 kB Download
RM367.10.fid.zip
md5:097bb0b00bc93a4bae610b004390b0c3
166.1 kB Download
RM367.11.fid.zip
md5:ba7d0e1c904aed513e9b0083e85ffa2f
221.8 kB Download
RM368.10.fid.zip
md5:7bb597f772e4f82e6ed74a16f0d7a9ee
167.8 kB Download
RM368.11.fid.zip
md5:46d38f6ebb1a2cea95d8fbd3a90aea8d
232.2 kB Download
RM369.10.fid.zip
md5:b5ea34f8703890806acba2108caf7ba1
168.1 kB Download
RM369.11.fid.zip
md5:6625591c6598cf618b09582d7b5361f2
227.5 kB Download
RM370B.10.fid.zip
md5:e3331a2babaa66fae755183049dcbbf9
161.7 kB Download
RM370B.11.fid.zip
md5:63a056165afc5d8f4a1a17b9aa8b527b
225.2 kB Download
RM370C_CARBON_01.fid.tar
md5:01851c7daa82f08981db5a85f23350ad
307.2 kB Download
RM370C_PROTON_01.fid.tar
md5:ac0f3275d8424058f3070f72a4802302
174.1 kB Download
RM371BF1.10.fid.zip
md5:151c2ba38e98f0b5f9447509c339ab0c
167.1 kB Download
RM371BF1.11.fid.zip
md5:ea15f7283479c27e8b30a9aee02fa4a9
223.5 kB Download
RM371BF2.10.fid.zip
md5:447bb39205d356e05dc02bcebd2bfdcb
165.9 kB Download
RM371BF2.21.fid.zip
md5:16347515d661a44c920f330e929fd592
224.8 kB Download
RM371C2_CARBON_01.fid.tar
md5:8d7489a4a15ee4d47e77072ee011f458
307.2 kB Download
RM371C2_CARBON_02.fid.tar
md5:98c508f8fcd04dba71145b1ef60393e6
307.2 kB Download
RM371C2_PROTON_01.fid.tar
md5:00365dac53f70236525180016f700e7c
174.1 kB Download
RM371C2_PROTON_02.fid.tar
md5:8b4bb84e08746615515ec1842ab4ffaa
174.1 kB Download
RM379.10.fid.zip
md5:3d7810a3dd2c6968c6069398161fcf30
168.2 kB Download
RM379.11.fid.zip
md5:56bc174543eb3e93a3fceee5130c5bb2
517.4 kB Download
RM379.12.fid.zip
md5:f2d4ea3b40780d39111832bfadccd2a0
210.7 kB Download
RM385-1-3.10.fid.zip
md5:d3af0e448f1582861f394c62f9b5bd61
165.8 kB Download
RM385-1-4.10.fid.zip
md5:a444f5c7156b95ee49a2a91d2b10f269
166.8 kB Download
RM385-2-2.10.fid.zip
md5:55b6ec9138f4b458481c7f638d18d99d
168.0 kB Download
RM385-2-3.10.fid.zip
md5:cdcf25ebb87f8480b6acbf26ebad41e0
167.4 kB Download
RM385-2-4.10.fid.zip
md5:17e205ff56e952b7cb5784475f9cd239
167.7 kB Download
RM385-2-5.10.fid.zip
md5:0db3868c835c426f1015f71d3b6d0d6f
169.8 kB Download
RM3851-2.10.fid.zip
md5:d19c3b7a0eda771714ca9f0faaa49dc4
170.9 kB Download
RM385_1_1.10.fid.zip
md5:fd64d4aeb33aeb654fe958c85c0000d6
170.3 kB Download
RM385_2_1.20.fid.zip
md5:2a8b100addd926397977221b4b6dfceb
175.0 kB Download
RM385B.10.fid.zip
md5:eea242967e7a8c690675da22a65fb967
166.3 kB Download
RM385B.11.fid.zip
md5:7ff827a2bfb6d15846980fd6a08d5c41
241.7 kB Download
RM386.10.fid.zip
md5:0b7c78c5e255241f13f9249e369923aa
182.0 kB Download
RM386.11.fid.zip
md5:e76608a505eaabd13fc053c87fbaef0b
239.1 kB Download
RM387.10.fid.zip
md5:33120df6c13339cb6806f0e443085d12
165.9 kB Download
RM387.11.fid.zip
md5:fe1d98e49a2d02ced134439451fa520d
524.9 kB Download
RM387.12.fid.zip
md5:e3b15019fb4dbd66c79192ecc6735db6
239.3 kB Download
RM388.10.fid.zip
md5:cfcd816fafc485386371f9f59b624d89
151.6 kB Download
RM388.11.fid.zip
md5:c840e4d4051be64b909f2abd8b864379
481.8 kB Download
RM388.12.fid.zip
md5:7009264cb3526c6efc8fe741efa4a617
233.0 kB Download
RM389.10.fid.zip
md5:8b407cd71e279e5c15ad0b36bc212eb2
162.0 kB Download
RM389.11.fid.zip
md5:a762581e32b6cb77bd02e5ebd0bc7b79
514.1 kB Download
RM389.12.fid.zip
md5:e74ee4e7cf6f840524a37eb6c8dfbd45
236.1 kB Download
RM390.10.fid.zip
md5:f6d23477b4add22e49a51567847fb2f6
183.1 kB Download
RM390.11.fid.zip
md5:dd445d2fb9e79f734ec621dec1441afc
230.6 kB Download
RM391.10.fid.zip
md5:7904530623ebacb9557915df5be20a3a
180.1 kB Download
RM391.11.fid.zip
md5:20c905bbc316091d1cbb3caf8c7a1078
234.8 kB Download
RM393.10.fid.zip
md5:97f76ccd0182e7c04772685a4d7ded6c
176.3 kB Download
RM393.11.fid.zip
md5:1c5ac9d04c21e506c6dd43e9ee903ffc
427.3 kB Download
RM394.10.fid.zip
md5:d949ddc49d7a27f0447b8a10cf8844b3
175.2 kB Download
RM394.11.fid.zip
md5:9a1b04472fb2d46bf1b56e82868a8872
431.8 kB Download
RM395.12.fid.zip
md5:22080a99942f222b4920b5bb5f6b9d5c
229.7 kB Download
RM402.10.fid.zip
md5:f1f26a79d2cdf251f4b872e409fe6110
170.4 kB Download
RM402.11.fid.zip
md5:333d2422d94757bb3f8e228b394a4e18
517.8 kB Download
RM402.12.fid.zip
md5:918d169478a5f624de402b6595a45a88
227.1 kB Download
RM403_1.10.fid.zip
md5:560e652424f4f98de44df801863dfe12
172.8 kB Download
RM403_1.11.fid.zip
md5:8592f06bb4b72b6dd8d06557f7d588e7
530.3 kB Download
RM403_1.zip
md5:8c8ff4218c6089d97029fcf5a44954b3
240.4 kB Download
RM403_2.10.fid.zip
md5:4b900853d5f27bf58cd19391b23cf71e
155.2 kB Download
RM403_2.11.fid.zip
md5:c3ace6a8e7ea76a17b5e80502c007d1f
500.6 kB Download
RM403_2.12.fid.zip
md5:8dd0bf08efbdb22c2498988dab257e88
224.5 kB Download
RM404.10.fid.zip
md5:6a670d52e3bb9a21f637bad96c1bb8c7
166.6 kB Download
RM404.11.fid.zip
md5:70cdc5e79d556d40fe54dc94b4685c25
507.0 kB Download
RM404.12.fid.zip
md5:f283d3bc02f694367a482aa4070a8867
227.3 kB Download
RM444.10.fid.zip
md5:01227607415777c20713a3f0dab6cfbb
175.9 kB Download
RM444.11.fid.zip
md5:cb013962d265619e6bbe092185799f01
239.6 kB Download
RM_356B_PROTON_01.fid.tar
md5:9ceeea0caf3e83d49f0ce03cb25ef700
174.1 kB Download
RM_394_1_PROTON_01.fid.tar
md5:ae2559d9ac81a2a4fecc7f9420c119fa
174.1 kB Download
148
705
views
downloads
All versions This version
Views 148148
Downloads 705705
Data volume 158.8 MB158.8 MB
Unique views 136136
Unique downloads 534534

Share

Cite as