AlF-NOTA-octreotide
A fluorine-18 octreotide tracer that matched, then beat, gallium-68 scans for neuroendocrine tumours in a multicentre trial
AlF-NOTA-octreotide is octreotide, the long-acting somatostatin drug, fitted with a small cage that grips fluorine-18 bound to aluminium. Injected before a PET scan, it collects on the somatostatin receptors that neuroendocrine tumours carry and shows where they are. Fluorine-18 is made in cyclotrons in large batches, so the tracer avoids the supply limits of the gallium-68 agents now standard. A Belgian-led trial found it detected more tumour lesions than gallium-68 tracers, and Chinese centres use it for rarer tumours. It is not approved anywhere.
Used in human trials: 4 MBq/kg, Single bolus injection, Intravenous (Trial: safety and dosimetry, 6 volunteers and 6 patients) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Somatostatin receptor PET is the standard way to image well-differentiated neuroendocrine tumours, which grow from hormone-making cells and usually carry many somatostatin receptors. The usual tracers are octreotide-type peptides carrying gallium-68. Gallium-68 comes from a generator that yields only a few doses a day, which limits how many patients a centre can scan and makes the scans expensive. Fluorine-18, the isotope in ordinary FDG scans, can be made in large amounts by a cyclotron and shipped, so researchers have looked for ways to attach it to somatostatin peptides.
AlF-NOTA-octreotide does it with aluminium. Fluorine-18 binds aluminium tightly, and the aluminium-fluoride unit is then held by NOTA, a ring-shaped chelator attached to octreotide. A Leuven group published an automated production method that meets good manufacturing practice: about 40 minutes per run, roughly 10.8 GBq per batch, and a product stable for at least six hours, enough to supply distant PET centres. In rats it collected specifically in receptor-rich organs. A cousin, SiTATE, reaches fluorine-18 by silicon chemistry instead.
Human testing followed a standard path. In 2020 the first prospective trial gave 4 MBq/kg to six healthy volunteers and six patients: the injection was safe and well tolerated, the effective dose was 22.4 µSv per MBq, with the spleen, bladder wall and kidneys receiving the most, and the pattern of normal uptake matched gallium-68 DOTATATE. Tumour uptake values were lower than with DOTATATE, but contrast against background and the share of lesions found were similar.
The decisive study was a prospective multicentre trial in 75 patients who had a routine gallium-68 DOTATATE or DOTANOC scan within three months. Scored by masked readers, AlF-NOTA-octreotide found 4,278 lesions against 3,454, a mean detection ratio of 91.1% against 75.3%, clearing the pre-set non-inferiority margin and showing superiority, with higher tumour-to-background contrast; bone was the one site where it was not ahead. In the same patients it changed TNM stage in 13% and management in 13%, every change caused by extra lesions it found, and simultaneous MRI confirmed more than 90% of the lesions only it detected as real. Readers agreed with each other as well as with gallium-68 scans and rated its images higher.
Leuven moved it into routine use in 2023. In 288 patients and 322 scans over ten months, the mean injected activity was about 209 MBq and uptake was strong across tumour grades and sites, including grade 3 tumours and lung tumours. Chinese centres report the same tracer in very different settings: in high-grade tumours and carcinomas it was positive in 93% of 42 patients and complemented FDG PET; in tumour-induced osteomalacia, a rare bone disease caused by small hormone-secreting tumours, scans were positive in 14 of 17 patients, and removing the tumours found brought phosphate back to normal; and in children with neuroblastoma it found far more bone metastases than MIBG scintigraphy, with uptake matching receptor staining in the tissue.
Uptake is not specific to tumours. Spleen, adrenals, kidneys, pituitary and liver take it up normally, and fractures, inflammation and other benign lesions can too, so findings are read with the clinical picture; a case report describes uptake in a gastrointestinal stromal tumour mistaken for a pancreatic neuroendocrine tumour. Despite the trial results, it has no FDA or EMA approval, and in the US the approved somatostatin receptor PET agents remain gallium-68 dotatate and copper-64 dotatate.
Mechanism of Action
AlF-NOTA-octreotide carries fluorine-18 to somatostatin receptors, so receptor-rich tumours show on a PET scan.
Somatostatin receptor binding
The octreotide core binds somatostatin receptors, mainly subtype 2; uptake tracked SSTR2 staining in neuroblastoma tissue.
Aluminium-fluoride labelling
Fluorine-18 bound to aluminium is captured by the NOTA ring, so the tracer can be made in batches by an automated synthesiser.
Distribution and clearance
Normal uptake is high in spleen, adrenals, kidneys and pituitary; it leaves in urine, so the bladder wall and kidneys get much of the dose.
Published Research
These are studies of AlF-NOTA-octreotide read from their PubMed abstracts: the phase 1 and multicentre trials from Leuven with their secondary analyses, routine-use and biodistribution series, Chinese studies in high-grade tumours, osteomalacia and neuroblastoma, a case report and the production method.
First trial: safety, dosimetry and a first comparison
Six healthy volunteers and six patients received 4 MBq/kg. It was safe and well tolerated; the spleen received the highest dose (0.159 mGy/MBq) and the effective dose was 22.4 µSv/MBq. Tumour SUVmax was lower than with gallium-68 DOTATATE (12.3 against 18.3), but tumour-to-background ratio and detection ratio (90.1% against 86.0%) did not differ significantly.
Multicentre non-inferiority trial
75 patients with a recent gallium-68 DOTATATE or DOTANOC scan were imaged 2 hours after 4 MBq/kg. It found 4,278 lesions against 3,454; mean detection ratio was 91.1% against 75.3%, a 15.8-point difference whose lower confidence limit cleared the −15% non-inferiority bound. Bone was the exception (−2.8%), and tumour-to-background ratio was higher (31.7 against 25.1).
Effect on staging and treatment
In the same 75 patients a multidisciplinary board reviewed each scan blind. Using this tracer instead of gallium-68 changed TNM stage in 10 (7 up, 3 down) and management in 10 (7 major changes), every difference due to extra lesions it detected; 86.7% saw no change.
Checked against simultaneous MRI
Ten patients had whole-body PET/MRI with this tracer and a standard gallium-68 DOTATATE PET/CT. Detection ratio was 99.1% against 91.4%, and MRI confirmed 96.2% of its 193 lesions, including 91% of the 33 lesions found only on its scan.
Reader agreement
Five readers assessed the 75 trial patients' scans. Agreement on lesion characterisation (0.921 against 0.934), lesion counts and Krenning scores was nearly identical for both tracers, and its images scored higher for overall quality (4.22 against 3.86).
Routine use in 288 patients
All somatostatin receptor scans at one centre from March 2023 to January 2024: 322 scans, 4,677 lesions. Mean injected activity was 208.5 MBq with about 121 minutes of uptake time. Grade 3 tumours (mean SUVmax 19.0) took up as much as low-grade ones, as did lung tumours; gastric tumours had the highest values.
Normal biodistribution in 162 patients
High physiological uptake in the spleen, adrenals, kidneys, pituitary and liver; moderate in the pancreatic uncinate process, prostate, thyroid and uterus. Neuroendocrine tumours took up more than fractures, inflammation and other benign lesions, though the ranges overlapped, and uptake related to tumour grade.
High-grade tumours and carcinomas
In 42 patients with grade 3 tumours or carcinomas it was positive in 92.9%, with uptake above liver in two-thirds. In 36 who also had FDG PET, each tracer found lesions the other missed (109 against 56); together they found 89.1% of 678 lesions.
Gut and pancreatic tumours against FDG
In 37 patients with paired scans it upstaged the T stage in two-thirds of those being staged and was better in half of those being restaged. It was more sensitive than FDG for lesions under 2 cm, including those of 0.5 cm or less, with median SUVmax 11.3 against 2.1.
Finding the tumour in osteomalacia
In 17 patients with suspected tumour-induced osteomalacia, scans were positive in 14, and surgery removed confirmed causative tumours, after which phosphate normalised. Sensitivity was 87.5%, specificity 100%; findings changed management in 88.2%.
Neuroblastoma against MIBG
In 74 children treated for neuroblastoma, detection per patient was similar, but per lesion it found 95.6% against 56.6% for MIBG SPECT/CT overall and 96.4% against 56.6% for bone metastases.
Neuroblastoma tissue check
In 71 biopsied lesions, uptake was higher in neuroblastoma than in ganglioneuroblastoma or ganglioneuroma, 77.9% of PET-positive lesions were SSTR2-positive by staining, and uptake correlated with the staining scores (rho 0.43 to 0.60) in neuroblastoma only.
A false lead in the pancreas
A 45-year-old man scanned for a suspected pancreatic neuroendocrine tumour had an avid mass below the pancreatic head that proved, after surgery, to be a low-risk gastrointestinal stromal tumour.
Automated GMP production
Three validation runs on an automated synthesiser gave 10.8 GBq per batch in 40 minutes at 26% yield, with radiochemical purity of 96% held for 6 hours. In healthy rats it was stable in the body and concentrated in receptor-expressing organs.
Dosing Data
AlF-NOTA-octreotide has no approved label. These are radioactive activities given in published human studies, each a single injection before a PET scan.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no regulator's label that says in what form AlF-NOTA-octreotide is supplied. It is a radioactive drug: the next part says where it is prepared and given.
Mixing a vial: a worked example
Nothing to mix at home, and no syringe units to work out: AlF-NOTA-octreotide is a radioactive drug, prepared and given in nuclear-medicine departments, and its dose is an amount of radioactivity (MBq or GBq), not a weight.
This page's dosing note: “AlF-NOTA-octreotide is dosed by radioactivity, by body weight in the trials, and produced in a radiopharmacy before the scan; no reconstitution maths applies.”
Source: this page's own note in Dosing Data below; the amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label on file says how AlF-NOTA-octreotide is stored. It is a radioactive drug held by the nuclear-medicine department that prepares and gives it (see the part above); the home rules for a mixed vial in the mixing guide do not apply to it.
How it is taken
As it was given in human studies: Intravenous (Single bolus injection; Trial: safety and dosimetry, 6 volunteers and 6 patients).
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Trial: safety and dosimetry, 6 volunteers and 6 patients: Scans up to 300 minutes after injection; Trial: multicentre comparison with gallium-68 tracers, 75 patients: Whole-body PET 2 hours later; Study: routine scans, 288 patients: PET about 2 hours later.
When effects appear: unknown; no source on this page gives a time to effect for AlF-NOTA-octreotide. Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Safe and well tolerated in six volunteers and six patients (PMID 32617641); Radiation exposure: an effective dose of 22.4 µSv per MBq, with the spleen, bladder wall and kidneys receiving the most (PMID 32617641); Uptake in benign lesions such as fractures and inflammation, which can be mistaken for tumour (PMID 34231107). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping AlF-NOTA-octreotide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the studies above”).
Interactions
Unknown: a PubMed search for human interaction studies of AlF-NOTA-octreotide (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of AlF-NOTA-octreotide products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against AlF-NOTA-octreotide's expected mass, 1,304.5 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: In Clinical Trials (Not approved: Drugs@FDA and the EMA medicines list hold no record (searched October 29, 2026)). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the studies above.
Contraindications & Cautions
No approved label exists, so there are no official contraindications. Points from the studies above:
Legal Status
AlF-NOTA-octreotide is an investigational PET tracer, not approved by FDA or the EMA.
Frequently Asked Questions
?What is AlF-NOTA-octreotide?
A PET tracer: octreotide with a NOTA chelator that holds fluorine-18 bound to aluminium. It shows where tumours carrying somatostatin receptors are.
?Why use fluorine-18 instead of gallium-68?
Fluorine-18 is made in cyclotrons in large batches and lasts long enough to ship, while gallium-68 comes from small generators that yield a few doses a day. One automated run produced about 10.8 GBq.
?Is it as good as gallium-68 scans?
In a 75-patient multicentre trial it found more lesions than gallium-68 DOTATATE or DOTANOC (91.1% against 75.3% detection ratio), meeting its non-inferiority goal, though not in bone.
?Is it approved?
No. FDA and the EMA hold no record of it. It is used in studies, in routine care at University Hospitals Leuven since 2023, and in clinical series from Chinese hospitals.
?What else is it used for?
Locating the small tumours behind tumour-induced osteomalacia, imaging neuroblastoma in children, and high-grade neuroendocrine tumours alongside FDG PET.
References
- [other] PubChem CID 171934829 (NOTA-Octreotide): formula C61H85N13O15S2, molecular weight 1304.5 (the unlabelled conjugate). Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/171934829
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT04552847 (phase 2/3, neuroendocrine tumours, completed); NCT03883776 (phase 1, completed).
- [clinical-trial] Pauwels E, et al. "[(18)F]AlF-NOTA-octreotide PET imaging: biodistribution, dosimetry and first comparison with [(68)Ga]Ga-DOTATATE in neuroendocrine tumour patients." Eur J Nucl Med Mol Imaging, 2020;47(13):3033-3046. PMID: 32617641.
- [clinical-trial] Pauwels E, et al. "(18)F-AlF-NOTA-Octreotide Outperforms (68)Ga-DOTATATE/NOC PET in Neuroendocrine Tumor Patients: Results from a Prospective, Multicenter Study." J Nucl Med, 2023;64(4):632-638. PMID: 36265911.
- [clinical-trial] Leupe H, et al. "Clinical impact of using [(18)F]AlF-NOTA-octreotide PET/CT instead of [(68)Ga]Ga-DOTA-SSA PET/CT: Secondary endpoint analysis of a multicenter, prospective trial." J Neuroendocrinol, 2024;36(8):e13420. PMID: 38837825.
- [clinical-trial] Boeckxstaens L, et al. "Prospective comparison of [(18)F]AlF-NOTA-octreotide PET/MRI to [(68)Ga]Ga-DOTATATE PET/CT in neuroendocrine tumor patients." EJNMMI Res, 2023;13(1):53. PMID: 37261615.
- [clinical-trial] Leupe H, et al. "Comparison of inter- and intraobserver agreement between [(18)F]AlF-NOTA-octreotide and [(68)Ga]Ga-DOTA-SSA PET/CT." EJNMMI Rep, 2025;9(1):17. PMID: 40369319.
- [pubmed] Leupe H, et al. "Evaluation of [¹⁸F]AlF-NOTA-octreotide PET/CT in routine clinical use: a retrospective analysis in 288 neuroendocrine tumor patients." Eur J Nucl Med Mol Imaging, 2026;53(11):6569-6582. PMID: 42332192.
- [pubmed] Hou J, et al. "Biodistribution of (18)F-AlF-NOTA-octreotide in Different Organs and Characterization of Uptake in Neuroendocrine Neoplasms." Mol Imaging Biol, 2021;23(6):827-835. PMID: 34231107.
- [pubmed] Hou G, et al. "¹⁸F-AlF-NOTA-octreotide PET/CT in high-grade G3 neuroendocrine tumors and neuroendocrine carcinomas: diagnostic performance and complementarity with ¹⁸F-FDG PET/CT." Eur J Nucl Med Mol Imaging, 2026;53(4):2351-2361. PMID: 41134321.
- [pubmed] Chen D, et al. "The clinical benefits of [(18)F]AlF-NOTA-octreotide PET/CT in staging and restaging patients with gastroenteropancreatic neuroendocrine neoplasms: comparison of [(18)F]FDG PET/CT." BMC Med Imaging, 2025;25(1):280. PMID: 40646449.
- [pubmed] Long T, et al. "Utility of 18F-AlF-NOTA-Octreotide PET/CT in the Localization of Tumor-Induced Osteomalacia." J Clin Endocrinol Metab, 2021;106(10):e4202-e4209. PMID: 33864458.
- [pubmed] Liu Y, et al. "Superior lesion detection with (18)F-AlF-NOTA-octreotide PET/CT compared to (123)I-MIBG SPECT/CT in neuroblastoma." Quant Imaging Med Surg, 2025;15(8):6948-6958. PMID: 40785938.
- [pubmed] Liu Y, et al. "Pathological validation of (18)F-AlF-NOTA-octreotide PET/CT for neuroblastoma." Sci Rep, 2025;15(1):34802. PMID: 41053346.
- [pubmed] Xu X, et al. "Uptake of (18)F-AlF-NOTA-octreotide PET/CT in gastrointestinal stromal tumors." EJNMMI Rep, 2026;10(1). PMID: 42026400.
- [pubmed] Tshibangu T, et al. "Automated GMP compliant production of [(18)F]AlF-NOTA-octreotide." EJNMMI Radiopharm Chem, 2020;5(1):4. PMID: 31997090.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Regulatory and registry status comes from Drugs@FDA (openFDA), the EMA medicines list and ClinicalTrials.gov, searched the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.