DOTA-MGS5
A stabilised minigastrin peptide for scanning medullary thyroid cancer and other tumours that carry the gastrin receptor
DOTA-MGS5 is a minigastrin analogue redesigned at its receptor-binding end so that enzymes in the blood break it down less. It binds the cholecystokinin-2 (gastrin) receptor, found in large amounts on medullary thyroid cancer, some lung neuroendocrine tumours and small cell lung cancer. A 12-patient phase 1/2a study of the gallium-68 version found it safe and good at showing medullary thyroid cancer, but of little use in gut and pancreatic neuroendocrine tumours. Lutetium-177 DOTA-MGS5 has been given to single patients. It is not approved.
Used in human trials: 180 MBq, Single injection, Intravenous (Gallium-68 DOTA-MGS5 PET, phase 1/2a (12 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?
Gastrin and the smaller minigastrin bind the cholecystokinin-2 receptor (CCK2R), which medullary thyroid cancer and several other tumours carry in large numbers. Radiolabelled minigastrins have been tried as tracers for years, but they were broken down quickly in the blood or built up in the kidneys. DOTA-MGS5, described in 2019, swaps two residues at the receptor-binding end for unnatural ones, N-methylnorleucine and 1-naphthylalanine. In mice its lutetium form stayed at least 70% intact in blood for an hour, and tumours took up about a fifth of the injected activity per gram.
A note on the structure: the 2019 design paper and the 2023 clinical report end the peptide at 1-naphthylalanine amide, and PubChem's formula fits that version. Two 2025 trial abstracts print an extra phenylalanine after it; this page follows the design paper.
In people, the gallium-68 PET tracer came first. A retrospective look at six patients with advanced medullary thyroid cancer found 87 suspicious lesions, with uptake higher two hours after injection than at one. The prospective phase 1/2a pilot study then gave 180 MBq to 12 patients, six with medullary thyroid cancer and six with other neuroendocrine tumours. It was well tolerated, with minor reactions in three; most of the tracer left the blood within hours through the kidneys. In medullary thyroid cancer it found about as many lesions as the standard F-DOPA scan, with higher uptake; in two lung neuroendocrine tumours it showed 26 lesions, but in gut and pancreatic tumours it lit up only 1 of 21.
The therapy version is at the single-patient stage. A first patient-specific dosimetry study in a patient with small cell lung cancer calculated a mean tumour dose of 12.5 Gy per GBq with low predicted toxicity, and a 2026 report describes a patient with extensive small cell lung cancer who received four cycles totalling 17.2 GBq and whose symptoms improved. In tissue samples, 16 of 42 small cell lung cancers had moderate to high receptor levels. DOTA-MGS5 is made in hospital radiopharmacies and given in nuclear-medicine departments; it has no FDA or EMA approval and is not a product for personal use.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Mechanism of Action
DOTA-MGS5 is a carrier. Its peptide end binds the cholecystokinin-2 receptor and is taken into the cell; the metal in its DOTA ring is imaged (gallium-68) or irradiates the tumour (lutetium-177).
Built to resist enzymes
N-methylnorleucine and 1-naphthylalanine at the C-terminus made the indium-111 and lutetium-177 forms far more stable in blood and tissue extracts over 24 hours (2019 study).
CCK2 receptor uptake
Taken up by over 60% of receptor-bearing cells at 4 hours, with negligible uptake in cells lacking the receptor (2019 study).
Gallium-68 PET
Cleared quickly from blood, mainly through the kidneys; the bladder wall, stomach wall and kidneys received the highest doses (2025 study).
Published Research
These are the studies of DOTA-MGS5 read from their PubMed abstracts on October 29, 2026: five reports in patients (two papers from one 12-patient phase 1/2a study, a six-patient retrospective series and two lutetium-177 reports that each include one patient), and two studies in cells and animals.
Phase 1/2a: safety and radiation dose, 12 patients
Twelve patients with medullary thyroid cancer or other neuroendocrine tumours received a single 180 MBq injection. Minor drug reactions occurred in three. Less than 21% of the activity remained in blood at about 3.5 hours and over 40% was in the urine by 3 hours. The effective dose was 0.023 mSv per MBq, and scans at 1 and 2 hours worked best.
Phase 1/2a: how well it finds tumours
In medullary thyroid cancer, four of six patients had positive lesions; the tracer found 48 lesions against 51 with F-DOPA, with higher uptake (mean SUVmax 7.2 against 4.7). In two lung neuroendocrine tumours it showed 26 lesions; in four gut and pancreatic tumours it showed only 1 of 21 lesions seen with gallium-68 DOTATOC.
First six patients with medullary thyroid cancer
A retrospective analysis of six patients found 87 lesions judged malignant: 2 local recurrences, 8 lymph node, 27 liver and 50 bone lesions. Uptake was higher at 2 hours than at 1 hour (mean SUVmax 7.2 against 6.0).
Lutetium-177 version: production and first dosimetry
Five automated batches met quality specifications at over 98% radiochemical purity. Mouse data supported treatment, and dosimetry in one patient with small cell lung cancer gave a mean of 12.5 Gy per GBq to measurable tumours (range 1.2 to 28) with a low predicted risk of toxicity.
First lutetium-177 treatment in small cell lung cancer
In cells, lutetium-177 DOTA-MGS5 was taken inside and reduced survival with rising activity. In 42 tumour samples, 16 had moderate to high receptor levels. A patient with extensive small cell lung cancer, positive on gallium-68 PET, received four cycles totalling 17.2 GBq, and symptoms improved.
Design and mouse studies
Labelled with indium-111, gallium-68 or lutetium-177, DOTA-MGS5 resisted enzyme breakdown, kept receptor affinity, and was taken up by over 60% of receptor-positive cells at 4 hours. In mice, tumours with the receptor took up about 20% of the injected activity per gram, with tumour-to-kidney ratios of 4 to 6.
Preclinical package for the first trial
Automated gallium-68 production met European Pharmacopoeia-based specifications. The tracer bound only its target receptor in cells, mouse data predicted about 0.01 mSv per MBq in humans, and a rat toxicity study set a maximum starting peptide amount of 50 µg.
Dosing Data
DOTA-MGS5 has no approved label. It is dosed by radioactivity and injected into a vein in a nuclear-medicine department. The rows below are the activities stated in the human studies carded above.
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.
Side Effects & Contraindications
Reported Side Effects
From the human studies above.
Contraindications & Cautions
No approved label exists, so there are no official contraindications. Points from the studies:
Legal Status
DOTA-MGS5 is investigational in every jurisdiction checked.
Frequently Asked Questions
?What is DOTA-MGS5?
A minigastrin analogue with two unnatural amino acids at its receptor-binding end and a DOTA chelator, made to carry gallium-68 or lutetium-177 to tumours with the cholecystokinin-2 receptor.
?Which tumours does it show?
In the first trial it showed medullary thyroid cancer and lung neuroendocrine tumours well, but very few gut or pancreatic neuroendocrine tumours.
?How much is injected for a scan?
About 180 MBq of gallium-68 DOTA-MGS5 in the phase 1/2a study, imaged one and two hours later.
?Is DOTA-MGS5 approved?
No. It is investigational; the treatment version has been given only to single patients so far.
References
- [other] PubChem CID 162659624, DOTA-MGS5: formula C70H92N14O20, molecular weight 1449.6. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/162659624
- [clinical-trial] von Guggenberg E, et al. "Safety, Biodistribution, and Radiation Dosimetry of the (68)Ga-Labeled Minigastrin Analog DOTA-MGS5 in Patients with Advanced Medullary Thyroid Cancer and Other Neuroendocrine Tumors." J Nucl Med, 2025;66(2):257-263. PMID: 39819687.
- [clinical-trial] Uprimny C, et al. "Diagnostic Performance of the (68)Ga-Labeled Minigastrin Analog DOTA-MGS5 in Patients with Advanced Medullary Thyroid Cancer and Other Neuroendocrine Tumors." J Nucl Med, 2025;66(10):1581-1588. PMID: 40876951.
- [pubmed] von Guggenberg E, et al. "Preliminary Clinical Experience with Cholecystokinin-2 Receptor PET/CT Using the (68)Ga-Labeled Minigastrin Analog DOTA-MGS5 in Patients with Medullary Thyroid Cancer." J Nucl Med, 2023;64(6):859-862. PMID: 36657979.
- [pubmed] Zavvar TS, et al. "Radiopharmaceutical formulation and preliminary clinical dosimetry of [(177)Lu]Lu-DOTA-MGS5 for application in peptide receptor radionuclide therapy." Eur J Nucl Med Mol Imaging, 2025;52(4):1321-1331. PMID: 39643727.
- [pubmed] Zavvar TS, et al. "Paving the Way for CCK2R-Targeted Peptide Receptor Radionuclide Therapy with [(177)Lu]Lu-DOTA-MGS5 in Patients with Small Cell Lung Cancer." Pharmaceutics, 2026;18(1). PMID: 41599245.
- [pubmed] Klingler M, et al. "DOTA-MGS5, a New Cholecystokinin-2 Receptor-Targeting Peptide Analog with an Optimized Targeting Profile for Theranostic Use." J Nucl Med, 2019;60(7):1010-1016. PMID: 30530828.
- [pubmed] Hörmann AA, et al. "Radiopharmaceutical Formulation and Preclinical Testing of (68)Ga-Labeled DOTA-MGS5 for the Regulatory Approval of a First Exploratory Clinical Trial." Pharmaceuticals (Basel), 2021;14(6). PMID: 34208516.
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT06155994 (phase 1/2, gallium-68 DOTA-MGS5 PET/CT in advanced neuroendocrine tumours, completed).
Sources & Citations
Studies were read from their PubMed records on October 29, 2026. Regulatory status comes from Drugs@FDA and the EMA medicines list (searched October 28, 2026) and the trial listing from ClinicalTrials.gov. Formula and weight are PubChem's. 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. Consult a licensed healthcare provider before making health decisions.