FAPI radiotracers

FAPI-04, FAPI-46, FAPI-74 (quinoline-based inhibitors); Ga-68 FAPI, F-18 FAPI-74, Lu-177 FAPI-46; FAP-2286 (a true cyclic peptide; Lu-177 FAP-2286 and Ga-68 FAP-2286); "FAP ligands"

Oncology & imaging

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: FAPI-04/46/74: quinoline-based small-molecule inhibitors (peptidomimetics) of fibroblast activation protein (FAP), with DOTA or related chelators. FAP-2286: cyclic peptide FAP ligand with DOTA. Labelled with Ga-68 or F-18 for PET, Lu-177/Y-90/Ac-225 for experimental therapy
Mechanism: Binds FAP, a protease on the surface of cancer-associated fibroblasts in the stroma of most solid tumours (and in some fibrotic and inflamed tissues); the isotope images or irradiates the tumour's supportive tissue rather than the cancer cells themselves
Routes studied: Intravenous only
Half-life: Ga-68 68 min; F-18 110 min; Lu-177 6.65 days. FAPI small molecules clear from blood very fast (minutes to hours) with short tumour retention — the limiting problem for therapy. FAP-2286 was designed for longer retention
Storage: Hospital or investigational radiopharmacy only
Regulatory status: Not approved anywhere; Ga-68 FAPI-46 and F-18 FAPI-74 in Phase 2/3 imaging trials; registration applications †

Doses are as reported in studies or by the community — never recommendations.

1What it is

Fibroblast activation protein is an enzyme that sits on activated fibroblasts: the supportive cells that build up around most cancers, in healing wounds, in arthritic joints and in scarring organs. Healthy adult tissue has almost none. In the late 2010s a group in Heidelberg converted a known FAP inhibitor into a chelator-bearing tracer, giving "FAPI" compounds that light up the stroma of a tumour on PET within minutes. Because more than 90% of epithelial cancers have FAP-rich stroma, the hope is for a near-universal cancer tracer that works where FDG PET is weak (low-grade tumours, brain, liver, peritoneum, high-background organs). Many institutional studies followed, and sponsored programmes are now running registration-aimed trials of Ga-68 FAPI-46 (in pancreatic cancer and others) and F-18 FAPI-74.

FAP-2286 is a different chemical entity — a cyclic peptide discovered by phage display — designed for the longer tumour retention a therapeutic needs.

2How it's thought to work

Stromal, not tumour-cell, targeting. uptake reflects how much activated stroma a tumour has, so dense desmoplastic cancers (pancreas, cholangiocarcinoma, gastric, breast lobular) light up strongly while some lymphomas and seminoma do not.

Fast kinetics. FAPI binds and dissociates quickly, giving sharp early images with low background. For therapy that is a drawback: much of the activity has left the tumour within a day.

Non-cancer uptake. fibrosis, healing fractures, arthritis, pancreatitis, myocardial injury after infarction and IgG4 disease all show uptake. This is a research opportunity (imaging fibrosis) and a diagnostic pitfall.

Therapeutic concept. irradiating the stroma could damage the tumour's scaffold and the cancer cells adjacent to it via beta-particle crossfire.

A ligand of fibroblast activation protein, which sits on the stroma around a tumour rather than on the tumour cell. Uptake reflects how much activated stroma there is, so dense cancers light up strongly.Schematic — not to scale

3What the research shows

Pan-cancer PET imaging

The first large series (80 patients, 28 tumour types) showed high uptake in sarcoma, oesophageal, breast, cholangiocarcinoma, lung and pancreatic cancers with very low background (Kratochwil 2019, J Nucl Med). Many prospective single-centre comparisons with FDG PET have followed; a 2021 systematic review reported higher sensitivity for primary tumours and metastases in several cancers, particularly gastric, pancreatic and peritoneal disease (Sollini 2021, Eur J Nucl Med Mol Imaging). Most studies are small and from a few centres. [2][4]

Graded B (Phase 2 ongoing)

Pancreatic cancer

Prospective studies report FAPI PET upstaging or changing management in a meaningful minority of patients compared with CT and FDG; a sponsored US Phase 2 of Ga-68 FAPI-46 in pancreatic cancer received FDA clearance to proceed (clinicaltrials.gov; trade press 2023–2024) †.

Radiotherapy planning and treatment response

Pilot studies in head and neck, lung and glioblastoma show FAPI PET altering target volumes; the clinical benefit is untested.

Graded B/C

Non-oncological imaging (cardiac fibrosis, IgG4 disease, arthritis)

Small prospective studies demonstrate uptake in post-infarct myocardium and fibrotic lung; prognostic value is being studied.

Graded B (small series, Phase 1)

Radioligand therapy

Lu-177 and Y-90 FAPI-46 in end-stage sarcoma and pancreatic cancer showed feasibility, modest responses and short tumour retention in small case series (Ferdinandus 2022, J Nucl Med). Lu-177 FAP-2286's Phase 1 (LuMIERE) reported tolerable safety and prolonged tumour retention with early signs of activity (Baum 2022, J Nucl Med — first-in-human; LuMIERE interim data †). [5][6]

4Reported side effects and interactions

Literature-reported

Literature (imaging). no significant adverse events reported across thousands of research scans; the main issues are interpretive (false positives from fibrosis, inflammation, healing bone, degenerative joints and uterine or breast physiological uptake).

Literature (therapy). limited data; haematological toxicity and fatigue in small series. FAP-2286 Phase 1 reported manageable toxicity, mostly haematological †. Because FAP is expressed in healing tissue, theoretical concerns include impaired wound healing and effects on bone marrow stroma with repeated cycles.

Community-reported

Community use. essentially none documented.

Interactions. none established. Recent surgery, radiotherapy or chemotherapy increase stromal/fibrotic uptake and can confound reading.

Markers researchers commonly monitor

No treatment markers apply to diagnostic use. In therapy trials:

Marker	Why it's watched
CBC	FAP is present on bone-marrow stromal cells; marrow toxicity is the main anticipated risk with Lu-177 FAPI or FAP-2286.
Creatinine/eGFR	renal excretion of the tracers.
Tumour markers specific to the cancer (CA19-9 in pancreatic, CEA, etc.)	response assessment alongside imaging.
Dosimetry after the first cycle	tumour retention time is the central question for FAPI therapy, so post-treatment imaging is built into protocols.
Wound healing status	a theoretical concern worth recording in trial populations.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Not applicable to individuals. Ga-68 FAPI tracers are labelled on site from generator eluate or produced under investigational kit protocols; F-18 FAPI-74 is cyclotron-produced and distributed. No calculator link is provided for this compound.

6Commonly studied alongside

FDG PET as the comparator in nearly every diagnostic study; PSMA ligands (#203) and DOTATATE (#201) as the theranostic models FAPI is trying to follow; RGD peptides (#207) as another stroma/vasculature-targeted class.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; Ga-68 FAPI-46 Phase 2 (pancreatic cancer and others) and F-18 FAPI-74 trials under IND; registration filing timing †
European Union	Not authorised; wide academic use under national compassionate or clinical-trial frameworks (notably Germany)
United Kingdom	Not licensed; research use
Australia	Not approved; research use at several centres
South Africa	Not registered; limited research use †
Sport (WADA)	Not listed

8Open questions

Will Ga-68 FAPI-46 or F-18 FAPI-74 reach approval, and for which indication, given that tumour-type-specific accuracy varies widely?
Can tumour retention be extended enough (FAP-2286, dimerised FAPIs, albumin-binding versions, alpha-emitters) to make therapy effective?
How to separate tumour stroma from benign fibrosis and inflammation on a scan.
Whether FAPI PET imaging of fibrosis (heart, lung, liver) has clinical value.

9References

1Lindner T et al. (2018). Development of quinoline-based theranostic ligands for the targeting of fibroblast activation protein. J Nucl Med. PubMed · DOI
2Kratochwil C et al. (2019). 68Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer. J Nucl Med. PubMed · DOI
3Giesel FL et al. (2019). 68Ga-FAPI PET/CT: biodistribution and preliminary dosimetry estimate of 2 DOTA-containing FAP-targeting agents in patients with various cancers. J Nucl Med. PubMed · DOI
4Sollini M et al. (2021). State-of-the-art of FAPI-PET imaging: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. PubMed · DOI
5Ferdinandus J et al. (2022). Initial clinical experience with 90Y-FAPI-46 radioligand therapy for advanced-stage solid tumors: a case series of 9 patients. J Nucl Med. PubMed · DOI
6Baum RP et al. (2022). Feasibility, biodistribution, and preliminary dosimetry in peptide-targeted radionuclide therapy of diverse adenocarcinomas using 177Lu-FAP-2286: first-in-humans results. J Nucl Med. PubMed · DOI
7Zboralski D et al. (2022). Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy. Eur J Nucl Med Mol Imaging. PubMed · DOI

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

31 Oct 2026Profile published — awaiting medical review

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