CP04
A minigastrin peptide built to carry a radioactive metal to medullary thyroid cancer, tested in 16 patients
CP04 is a synthetic version of minigastrin, a gut hormone fragment, with six D-glutamic acids at one end and a DOTA ring that holds a radioactive metal. It targets the cholecystokinin-2 receptor, which medullary thyroid cancer carries in large amounts. Labelled with indium-111 it was given to 16 patients in a European phase 1 trial, GRAN-T-MTC, which found it safe at both peptide amounts tested and positive on scans in 13. It is not approved anywhere.
Used in human trials: 10 µg or 50 µg peptide, Single injection at each step, Intravenous (Indium-111 CP04, medullary thyroid cancer, GRAN-T-MTC phase 1 (16 p...) 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?
Medullary thyroid cancer starts in the C-cells of the thyroid, the cells that make calcitonin. Once it has spread, scans often miss disease and treatment options are limited. Many of these tumours carry the cholecystokinin-2 receptor, also called the gastrin receptor, in large amounts, which makes it a target for the same 'find it, then irradiate it' approach used with somatostatin analogues in other neuroendocrine tumours. CP04 was chosen from a set of radiolabelled minigastrin analogues compared in a joint European project because, labelled with indium-111, it was stable, bound the receptor well, stayed in tumours and left little activity in the kidneys of animals.
The molecule is minigastrin with its natural L-glutamic acids swapped for six D-glutamic acids, plus a DOTA chelator. In rodents the swap gave better tumour-to-kidney ratios than the natural sequence, whose run of glutamic acids is linked to high kidney retention. Its methionine is prone to oxidation, so the freeze-dried kit made for the trial included methionine and gentisic acid as protectants; trace zinc in the filling process was another manufacturing hurdle. Rat and mouse toxicity tests set the safety margins for the first human doses.
GRAN-T-MTC gave indium-111 CP04 to 16 patients with advanced or metastatic medullary thyroid cancer, or a rapidly rising calcitonin, at two peptide amounts, 10 µg and 50 µg; the larger amount was the one considered suitable for later therapy. No serious adverse events occurred. Two patients had brief flushing and a fast heartbeat during injection, and a companion analysis found that the injection raised calcitonin about four to five times over baseline within minutes, as expected from a peptide that activates the receptor. Scans were positive in 13 of 16 patients, better than conventional imaging. Co-infusing Gelofusine, a gelatin plasma expander, roughly halved the radiation dose to the kidneys.
That is the whole human record: one phase 1 trial reported in two papers. The authors projected that a lutetium-177 version would deliver about 0.9 Gy to the kidneys per 7.4 GBq, but no therapy study with CP04 was found among the records read. CP04 is made in radiopharmacies and injected 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
CP04 is a carrier. The peptide end binds the cholecystokinin-2 receptor on tumour cells, and the metal in the DOTA ring is imaged or, in principle, irradiates the tumour.
CCK2 receptor binding
Receptor affinity and specific uptake into cells were the same whether it carried gallium-68 or lutetium-177; a docking model places the peptide's tail inside the receptor and the DOTA end outside (2018 study).
Receptor activation
Injected into patients it raised blood calcitonin within minutes and caused brief flushing in a few, consistent with its description as a receptor agonist (2025 study).
Imaging and kidney dose
Indium-111 CP04 scans found tumours in 13 of 16 patients; the bladder, kidneys and stomach wall received the highest doses (2023 study).
Published Research
These are the studies of CP04 read from their PubMed abstracts on October 29, 2026: two reports from one 16-patient phase 1 trial, two mouse and rat studies, and four laboratory papers on making and characterising it. Three records whose titles do not use the name (the calcitonin report, the enzyme-inhibitor study and the metal-labelling paper) are carded because their abstracts name CP04 as the agent tested.
GRAN-T-MTC phase 1 final results, 16 patients
Patients with advanced medullary thyroid cancer received indium-111 CP04 at 10 µg or 50 µg of peptide. There were no serious adverse events; two had transient tachycardia and flushing. The effective dose for 200 MBq was about 7 mSv at either amount. Gelofusine cut kidney dose by 53%. Scans were positive in 13 patients (81%) and outperformed conventional imaging.
Calcitonin and procalcitonin after injection
In the same 16 patients, calcitonin peaked at about 5.2 times baseline after the 10 µg amount and 4.1 times after 50 µg, and procalcitonin rose in parallel (r = 0.94). Mild, short side effects occurred in three injections. The authors suggest unlabelled CP04 could serve as a stimulation test.
Toxicity and dosimetry for trial approval
CP04 was well tolerated by mice and rats, with no observed adverse effect up to 89 µg/kg in rats. Indium-111 CP04 stayed over 70% intact in mouse blood at 5 minutes and reached about 9% of the injected dose per gram in receptor-positive tumours. Gelofusine lowered kidney uptake from 5.55 to 1.69%.
With an enzyme inhibitor in mice
Co-injecting phosphoramidon, which blocks neutral endopeptidase, made indium-111 CP04 more stable in mouse blood and nearly doubled tumour uptake at 4 hours (8.5 to 16.0% per gram). In this comparison the truncated analogue MG11 gained most from the inhibitor.
Freeze-dried kit for the first human trial
Kits holding 10 or 50 µg CP04 with ascorbic acid, gentisic acid and methionine labelled with indium-111 at over 94% radiochemical purity, stayed stable for more than 6 months, and the labelled product for over 4 hours. Methionine oxidation and trace zinc were the main problems solved.
How it sits in the receptor
Gallium and lutetium forms bound the receptor equally. A homology model put the peptide's C-terminal part inside the receptor and the DOTA-metal end outside, exposed to water, which would explain why the metal makes little difference to affinity.
Labelling with gallium, lutetium and yttrium
CP04 labelled with yttrium-90, lutetium-177 or gallium-68 at over 90% yield. Chromatography showed the gallium complex behaving differently from the lutetium and yttrium ones, suggesting different metal coordination, and revealed impurities including oxidised methionine.
Automated gallium-68 production
A synthesis module produced gallium-68 DOTA-CP04 reproducibly at over 70% decay-corrected yield, and the product met the acceptance criteria set for human injection.
Dosing Data
CP04 has no approved label. In the one human trial, indium-111 CP04 was injected into a vein in a nuclear-medicine department at two fixed peptide amounts; the radioactivity itself is not stated in the abstract beyond the 200 MBq used to express the effective dose.
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 phase 1 trial (16 patients).
Contraindications & Cautions
No approved label exists, so there are no official contraindications. Points from the studies:
Legal Status
CP04 is investigational in every jurisdiction checked.
Frequently Asked Questions
?What is CP04?
A DOTA-linked minigastrin analogue with six D-glutamic acids that binds the cholecystokinin-2 receptor, made to carry a radioactive metal to medullary thyroid cancer.
?Has it been tested in people?
Yes, in one phase 1 trial of 16 patients with medullary thyroid cancer. Indium-111 CP04 was safe at 10 µg and 50 µg and showed tumours in 13 of them.
?Why did patients flush after injection?
CP04 activates the receptor as well as binding it, and the injection briefly raised calcitonin; two patients had short-lived flushing and a fast heartbeat.
?Is CP04 approved?
No. It is investigational, and no treatment study with a therapeutic radionuclide has been published.
References
- [clinical-trial] Lezaic L, et al. "[(111)In]In-CP04 as a novel cholecystokinin-2 receptor ligand with theranostic potential in patients with progressive or metastatic medullary thyroid cancer: final results of a GRAN-T-MTC Phase I clinical trial." Eur J Nucl Med Mol Imaging, 2023;50(3):892-907. PMID: 36334104.
- [clinical-trial] Trofimiuk-Müldner M, et al. "Calcitonin and procalcitonin measurement after cholecystokinin-2/gastrin receptor agonist stimulation in patients with advanced medullary thyroid cancer: results from the GRAN-T-MTC study." Endokrynol Pol, 2025;76(3):321-330. PMID: 40586407.
- [pubmed] Maina T, et al. "Preclinical pharmacokinetics, biodistribution, radiation dosimetry and toxicity studies required for regulatory approval of a phase I clinical trial with (111)In-CP04 in medullary thyroid carcinoma patients." Eur J Pharm Sci, 2016;91:236-42. PMID: 27185299.
- [pubmed] Kaloudi A, et al. "Improving the In Vivo Profile of Minigastrin Radiotracers: A Comparative Study Involving the Neutral Endopeptidase Inhibitor Phosphoramidon." Cancer Biother Radiopharm, 2016;31(1):20-8. PMID: 26844849.
- [pubmed] Pawlak D, et al. "From preclinical development to clinical application: Kit formulation for radiolabelling the minigastrin analogue CP04 with In-111 for a first-in-human clinical trial." Eur J Pharm Sci, 2016;85:1-9. PMID: 26826279.
- [pubmed] Lipiński PFJ, et al. "Structural studies on radiopharmaceutical DOTA-minigastrin analogue (CP04) complexes and their interaction with CCK2 receptor." EJNMMI Res, 2018;8(1):33. PMID: 29663167.
- [pubmed] Maurin M, et al. "The radiometal makes a difference. Synthesis and preliminary characterisation of DOTA-minigastrin analogue complexes with Ga, Lu and Y." Nucl Med Rev Cent East Eur, 2015;18(2):51-5. PMID: 26315862.
- [pubmed] Haskali MB, et al. "Automated preparation of clinical grade [(68)Ga]Ga-DOTA-CP04, a cholecystokinin-2 receptor agonist, using iPHASE MultiSyn synthesis platform." EJNMMI Radiopharm Chem, 2019;4(1):23. PMID: 31659509.
- [registry] ClinicalTrials.gov API v2, read October 28, 2026: NCT03246659 (phase 1, radiolabelled CCK-2/gastrin receptor analogue in advanced medullary thyroid cancer, 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. 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.