Tracers / [18F]FDOPA

[18F]FDOPA

Also written as 6-[18F]fluoro-L-DOPA; [18F]dihydroxyphenylalanine; [18F]F-DOPA; [18F]FDOPA; [18F]Fluoro-DOPA; [18F]Fluoro-L-DOPA; [18F]fluorodopa
Radionuclide
F-18 t½ 109.7 min
Modality
PET
Production route
Cyclotron liquid target
Stage
Approved
Syntheses indexed
49

What it is

Compound class
Amino acid
Target / mechanism
System L (LAT1) amino-acid transport into cells; for dopaminergic imaging, subsequent decarboxylation by aromatic-L-amino-acid decarboxylase (AADC) PMID 30519867 / DOI 10.1007/s00259-018-4207-9; PMID 39384519 / DOI 10.1053/j.semnuclmed.2024.09.004
Clinical application
Parkinsonian syndromes; neuroendocrine tumours; congenital hyperinsulinism; glioma PMID 39384519 / DOI 10.1053/j.semnuclmed.2024.09.004
Theranostic pair

Regulatory status

FDA
Yes — 2019; Fluorodopa F 18; The Feinstein Institute for Medical Research; NDA 200655 Drugs@FDA, NDA 200655, approved 2019-10-10 — https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process&searchTerm=fluorodopa
EMA (centralised)
No EMA medicines register — no centrally authorised medicine containing fluorodopa (18F); search: https://www.ema.europa.eu/en/medicines?search_api_fulltext=fluorodopa
Other approvals
Not centrally authorised by EMA, but holds national marketing authorisations in multiple EU/EEA member states (national / decentralised / mutual-recognition procedures). Example (official national register): France — IASOdopa, fluorodopa (18F), marketing authorisation active since 16/11/2006, holder Curium Austria GmbH.
Brand names
Fluorodopa F 18 (US)

Clinical use

Typical injected activity
185-200 MBq PMID 30519867 / DOI 10.1007/s00259-018-4207-9 (Joint EANM/EANO/RANO/SNMMI practice guideline for PET imaging of gliomas with radiolabelled amino acids and FDG, v1.0 -- 'Administered activity in adults' table)
Uptake time
10-30 min post-injection for brain-tumour imaging (EANM/EANO/RANO glioma guideline) PMID 30519867 / DOI 10.1007/s00259-018-4207-9

Reported in the literature. Not a dosing recommendation.

Published syntheses

ModuleCassettePurificationYield %RCP %Precursor / supplierSource
Neptis Perform
ORA
vendor cassetteHPLC9.60% ± 3.61%
yes
>95%41437980
2025 Front Nucl Med
[18F]FDOPA was produced routinely via automated nucleophilic synthesis using the NEPTIS® Perform synthesizer module (ORA, Belgium) equipped with a commercially available cassette-based chemistry setup (ABX, Germany). — The decay corrected yield of [18F]FDOPA (n = 26) were 9.60% ± 3.61%.
TRACERlab FX N Pro
GE HealthCare
custom manifoldHPLC+SPE5.2 ± 0.5%
no
>99%3,4-OMOM-6-(BPin)DOPA(Boc)2-OtBu (8)
WuXi AppTec
39064920
2024 Molecules
these conditions were translated to the commercially available automated synthesis module TRACERlab FX N Pro (GE Healthcare) — The radiotracer was obtained with an activity yield (AY; isolated, not decay-corrected) of 5.2 ± 0.5% (n = 3)
In-house / custom built
in-house
custom manifoldHPLC+SPE3,4-OMOM-6-(BPin)DOPA(Boc)2-OtBu (8)
WuXi AppTec
39064920
2024 Molecules
Radiosynthesis was performed on...remote-controlled apparatus (in-house development)
Manual synthesiscustom manifoldHPLC30±3Boc2-6-Me3Sn-DOPA(MOM)2-OMe36214204
2023 Chemistry
Optimized procedure for radiofluorination of stannyl precursors: [18F]F− was loaded onto a QMA carbonate cartridge — Subsequent deprotection and HPLC isolation delivered the desired tracer in good AYs of 30±3 %.
Raytest SynChrom
Elysia-Raytest
custom manifoldHPLC+SPE15%≥97%ABX 1336, (S)-3-(5-Formyl-4-methoxymethoxy-2-nitro-phenyl)-2-(trityl-amino)-propionic acid tert-butyl ester
ABX
36678506
2022 Pharmaceuticals (Basel)
The synthesis and its modifications were carried out using a Raytest Synchrom R&D module. — with a radiochemical yield (RCY) of 15%, radiochemical purity (RCP) ≥ 97%, and enantiomeric purity (ee) ≥ 96%.
Neptis (model not stated)SPE11.8 ± 3.2%
yes
>95%ABX nitro precursor35607634
2022 Nucl Med Mol Imaging
NEPTIS module and a commercially available cassette based chemistry — The decay uncorrected yield were 5.5 ± 1.5% (n = 33) which corresponds to a decay corrected yield of 11.8 ± 3.2% (n = 33).
FASTlab 2SPE9.3-9.8%
no
>99.9%34513282
2021 Am J Nucl Med Mol Imaging
using a GE Fastlab 2 module — The uncorrected radiochemical yields of [18F]FDOPA were 9.3-9.8% with a total synthesis time of ~140 min.
31 ± 3%34018059
2021 EJNMMI Radiopharm Chem
AllinOne (AiO)
Trasis
vendor cassetteHPLC> 35%nitroveratraldehyde 1133689056
2021 EJNMMI Radiopharm Chem
The process was performed in a Trasis (Ans, Belgium) AllInOne automatic synthesis module cassette-based and provides 6-[18F]FDOPA with reproducible results — yielding 6-[18F]FDOPA with RCYs > 35%, Am 129,5 Gbq/μmol and ee of 97%
TRACERlab MX
GE HealthCare
SPE> 95%33689056
2021 EJNMMI Radiopharm Chem
The nucleophilic based method was firstly implemented in 2013 by Martin et al. to a GE (Chicago, Illinois, United States) TRACERlab MXFDG automated module
IBA IFP
IBA
vendor cassetteSPE20 ± 5%chiral precursor 37 (ABX 1336)
ABX
33689056
2021 EJNMMI Radiopharm Chem
The same process, using the non-carried precursor (ABX 1336) was also developed for an IBA (Louvain-la-neuve, Belgium) module within a set of disposable cassettes (IFP-“Integrated Fluidic Processor”) — with 20 ± 5% RCY and > 99% ee
iPHASE FlexLab
iPHASE Technologies
5-7%> 99%33689056
2021 EJNMMI Radiopharm Chem
The same method was performed in an automated model iPHASE FlexLab Module (Australia) by Ya-Yao Huang — RCY between 5 and 7% in 110 min
Modular-Lab Standard
Eckert & Ziegler
20 ± 1%33689056
2021 EJNMMI Radiopharm Chem
Pretze et al. (Pretze et al., 2017) evaluated the multistep synthesis based on cPTC and ABX methods using an Eckert&Ziegler (Berlin, Germany) modular-Lab Standard module — RCY of 20 ± 1%, Am up to 2.2 GBq/μmol and ee > 96%
TRACERlab MX
GE HealthCare
8-12%>95%33689056
2021 EJNMMI Radiopharm Chem
In 2013, Martin’s group automated this method for the GE TRACERLab MXFDG — reproducible RCY’s between 8 and 12%, in 100 min of reaction
TRACERlab MX
GE HealthCare
33689056
2021 EJNMMI Radiopharm Chem
Recently, Mossine et al. (Mossine, 2019) reported the automation of a copper-mediated, one-pot, high molar activity of 6-[18F]FDOPA using a GE TRACERlab MXFN
In-house / custom builtcustom manifoldHPLC9.3 ± 4.2%
no
97.4 ± 1.4%trimethylstannyl-precursor 2
ABX
34117961
2021 EJNMMI Radiopharm Chem
The synthesis is carried out using a custom-build synthesis platform — [18F]1 is obtained in a non-decay corrected (n.d.c.) RCY of 9.3 ± 4.2%, 45 min from the end of the second bombardment.
TRACERlab MX
GE HealthCare
vendor cassetteSPE5.6 ± 0.3%
no
98.4 ± 0.16%nitro-precursor 4
ABX
34117961
2021 EJNMMI Radiopharm Chem
The automated synthesis of [18F]1 is performed on a GE Tracerlab MX module — [18F]1 is obtained in a non-decay corrected RCY of 5.6 ± 0.3%, 95 min from EOB.
AllinOne (AiO)
Trasis
vendor cassetteHPLC30 ± 8%
no
99.8 ± 0.5%nitroveratraldehyde 734117961
2021 EJNMMI Radiopharm Chem
[18F]1 is synthesized using the Trasis AllinOne (AiO) automated radiochemistry module — [18F]1 is obtained in a non-decay corrected RCY of 30 ± 8%, 70 min from EOB.
33664973
2021 Neurooncol Pract
34053336
2021 J Cereb Blood Flow Metab
In-house / custom builtcustom manifoldHPLC+SPE54 ± 5%
yes
N,N,O,O'-tetraBoc-6-(SnMe3)DOPA-OEt
ABX
29244780
2017 Molecules
All automated radiosyntheses were carried out in a home-made synthesis module. — 6-[18F]FDOPA in a high RCY of 54 ± 5% (n = 5)
HPLC7±1 %nickel complex 4 a26478840
2015 ChemistryOpen
26478831
2015 ChemistryOpen
Raytest SynChrom
Elysia-Raytest
HPLC15 ± 5 %97 ± 36-trimethylstannyl-L-DOPA
ABX
29564384
2017 EJNMMI Radiopharm Chem
the synthesis module (Raytest, Synchrom FDOPA F2, see schematic overview in Fig. 1) — FDOPA-Lower 20Ne(d,α)18F single-shoot68 15 ± 5 8.5 ± 3.3 97 ± 3 526 ± 192
Raytest SynChrom
Elysia-Raytest
HPLC23 ± 4 %97 ± 36-trimethylstannyl-L-DOPA
ABX
29564384
2017 EJNMMI Radiopharm Chem
the synthesis module (Raytest, Synchrom FDOPA F2, see schematic overview in Fig. 1) — FDOPA-Higher 18O(p,n)18F double-shoot42 23 ± 4 121 ± 27 97 ± 3 4521 ± 967
42089130
2026 Neuro Oncol
TRACERlab FX FN
GE HealthCare
custom manifoldHPLC+SPE6 ± 1%>99%FDOPA BPin precursor (1)
ABX
32269382
2020 Nat Protoc
General Electric (GE) TRACERLab FXFN synthesis module — 3.85 ± 0.59 GBq, 104 ± 16 mCi, 6 ± 1% based upon approximately 66.6 GBq (1800 mCi) of starting [18F]fluoride
TRACERlab FX FN
GE HealthCare
custom manifoldHPLC+SPE5 ± 1%>98%FDOPA BPin precursor (1)
ABX
32269382
2020 Nat Protoc
This pre-purification requires a modified TRACERlab FXFN synthesis module (see Supplementary Figure 2 for configuration and Supplementary Method 1 for timelist) — 2.26 ± 0.48 GBq, 61 ± 13 mCi, 5 ± 1% based upon 45.6 ± 11.0 GBq (1232 ± 298 mCi) of starting [18F]fluoride
37026455
2023 J Cereb Blood Flow Metab
TRACERlab FX FNHPLC6 ± 1%>99%BPin precursor 1
ABX
31536095
2019 Org Biomol Chem
TRACERLab FXFN synthesis module — the activity yield (AY) was 6 ± 1%, based upon 1.8 Ci of [18F]fluoride
42620272
2026 Front Endocrinol (Lausanne)
Iason GmbH
42422425
2026 Front Endocrinol (Lausanne)
The radiochemical synthesis of [18F]fluoro-L-3,4-dihydroxyphenylalanine (18FDOPA) was commercially sourced from IASON GmbH (Graz, Austria).
39351526
2024 Front Endocrinol (Lausanne)
38871836
2024 Diabetologia
38341198
2024 BMJ Case Rep
HPLC15 ± 3%95.8 ± 1.4%nucleophilic precursor33153893
2021 Appl Radiat Isot
purified using in-built preparative HPLC on FX2N module — [18F]fluorodopa was synthesized with high radiochemical purity of 95.8 ± 1.4% with 15 ± 3% yield.
10~14%
yes
>95%32113705
2020 Appl Radiat Isot
iPHASE FlexLab module — Decay-corrected radiochemical yield (RCY) of [18F]FDOPA synthesized by this method was 10~14% (n = 7)
20±1%>98%AB133627886621
2017 Nucl Med Biol
an Ecker&Ziegler Modular-Lab Standard module — [18F]F-DOPA could be produced fully automated within 114min in RCYs of 20±1%
27943464
2017 Chemistry
HPLC36.3 ± 3.0%
yes
26011311
2015 J Labelled Comp Radiopharm
on a GE FASTlab synthesizer — [(18)F]FDOPA and [(18)F]FTYR were produced in 36.3 ± 3.0% (n = 8) and 50.5 ± 2.7% (n = 10) FASTlab radiochemical yield (decay corrected)
HPLC25851249
2015 Ann Nucl Med
Automatic synthesis of (18)F-FDOPA was based on the electrophilic method using TRACERlab FXFE module.
HPLC21344169
2011 Ann Nucl Med
>= 95%19433364
2009 Appl Radiat Isot
In a home-made automatic synthesizer, 9064+/-3076 MBq of [(18)F]FDOPA were produced within 120 min from EOB (n=5).
HPLC22%(2S,5S)-tert-butyl-5-(4-benzyloxy-2-fluoro-5-formylbenzyl)-2-tert-butyl-3-methyl-4-oxoimidazolidine-1-carboxylate19759110
2009 J Nucl Med
18344441
2008 J Nucl Med
HPLC25±3%
yes
N-formyl-3,4-di-tert-butoxycarbonyloxy-6-(trimethylstannyl)-L-phenylalanine ethyl ester18278215
2008 Nuklearmedizin
The TRACERlab Fx FDOPA module (GE Medical Systems) was used for the preparation of 6-[(18)F]fluoro-L-DOPA. — 6-[(18)F]fluoro-L-DOPA purified by HPLC was obtained in decay-corrected radiochemical yields of 25+/-3%
15693650
2005 Radiol Clin North Am
HPLC2-(2-Fluoro-4, 5-dimethoxybenzyl)-N-(diphenylmethylene) glycine tert-butyl ester (8)12579971
2001 Yao Xue Xue Bao
greater than 97%11065151
2000 Nucl Med Commun
The radiosynthesis was performed by the Scanditronix Anatech RB III robotic system.

Precursor

Common precursor
Nucleophilic route: protected nitro-precursor (e.g. nitro-aldehyde 'ABX 1336', (S)-3-(5-formyl-4-methoxymethoxy-2-nitro-phenyl)-2-(trityl-amino)-propionic acid tert-butyl ester) or nitroveratraldehyde; electrophilic route: enantiopure trimethylstannyl precursor PMID 34117961 / DOI 10.1186/s41181-021-00135-y; PMID 36678506 / DOI 10.3390/ph16010010
Suppliers seen in the literature
ABX advanced biochemical compounds (Radeberg, Germany)
Cited suppliers in indexed syntheses
ABX, Iason GmbH, WuXi AppTec
Typical final purification
HPLC (electrophilic route); SPE possible (nucleophilic)

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Quality control Pharmacopoeial monograph

Ph. Eur. monograph
1918 (electrophilic route); 2481 (nucleophilic route)
USP monograph
USP monograph: Fluorodopa F 18 Injection (referenced in FDA product labelling; not independently verified — USP-NF index is subscription-only)
AppearancepHRCP HPLCHPLC UVHPLC ECDResidual solvents (GC)Radionuclidic (HPGe)Half-lifeActivityEndotoxins (LAL)SterilityFilter integrity
How this set was arrived at. Base set per Ph. Eur. 0125. Related substances + [18F]fluoride by HPLC; catecholamine structure -> ECD (per draft note). FIX: 'Kryptofix' applies to the NUCLEOPHILIC route only (monograph 2481); the ELECTROPHILIC route (1918) uses no aminopolyether. Residual solvents (GC) apply to both routes.

Tests listed by reference only. Monograph texts are copyrighted and are not reproduced here. How these are derived

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Notes

Carbidopa premedication common. Both electrophilic and nucleophilic routes in clinical use.