The novel cholecystokinin-2 receptor (CCK2R) ligand [111In]In-CP04 appears to be an effective and safe therapeutic alternative for patients with medullary thyroid cancer (MTC), according to a recently published study in the European Journal of Nuclear Medicine and Molecular Imaging.

Due to the growing incidence and the high mortality associated with MTC, there is a great interest in new therapies that could help improve the 10-year relative survival rate of patients with MTC not eligible for surgical treatment, noted Luka Lezaic, from the University Medical Centre Ljubljana in Slovenia, and colleagues.

CCK2R and gastrin receptors are known to be overexpressed in MTC cells. Therefore, CCK2R-seeking ligands could represent a promising therapeutic alternative for patients with MTC diagnosed with advanced disease, the authors noted.


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Hence, the trial aimed to assess the safety and pharmacokinetics of 1 of these ligands: [111In]In-CP04. 

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The initial phase of the trial included 4 patients that received a low mass amount of 10 μg of [111In]In-CP04 as a safety step. After it was well tolerated, patients received the potential therapeutic dose of 50 μg. 

In the second phase, 16 patients received the 50 μg dose; furthermore, patients were divided into an arm that received gelofusine coadministration and a second arm that did not.

In the 4 months after the beginning of phase 1, control visits with exhaustive physical examination, vital sign assessment, electrocardiogram, and extensive laboratory testing, were performed to determine the safety profile of [111In]In-CP04.

Researchers acquired biodistribution and dosimetry data through computed tomography and single-photon emission computed tomography images, as well as blood and urine collection at regular time intervals. Only 2 patients experienced adverse effects during infusion, namely tachycardia and flushing. There were no significant laboratory changes during the trial period.

Dosimetry assessment showed the highest dose to the urinary bladder, kidneys, and stomach. Blood clearance was bi-exponential with an α-half-life of 12 minutes vs 34 minutes and a β-half-life of 114 minutes vs 262 minutes with and without gelofusine, respectively. Gelofusine administration significantly reduced the absorbed dose to the kidney.

“Administration of [111In]In-CP04 in patients with recurrent MTC is safe, even when high peptide mass is administered in advanced cases with extensive disease,” the authors concluded.

Reference

Lezaic L, Erba P, Decristoforo C, et al. [111In]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. Published online November 5, 2022. doi:10.1007/s00259-022-05992-6