Development of Highly Potent Clinical Candidates for Theranostic Applications against Cholecystokinin-2 Receptor Positive Cancers
- Author(s)
- Corlett, A; Pinson, JA; Rahimi, MN; Van Zuylekom, J; Cullinane, C; Blyth, B; Thompson, PE; Hutton, CA; Roselt, PD; Haskali, MB;
- Details
- Publication Year 2023-08-10,Volume 66,Issue #15,Page 10289-10303
- Journal Title
- Journal of Medicinal Chemistry
- Publication Type
- Research article
- Abstract
- Peptide receptor radionuclide therapy (PRRT) is a promising form of systemic radiation therapy designed to eradicate cancer. Cholecystokinin-2 receptor (CCK(2)R) is an important molecular target that is highly expressed in a range of cancers. This study describes the synthesis and in vivo characterization of a novel series of (177)Lu-labeled peptides ([(177)Lu]Lu-2b-4b) in comparison with the reference CCK(2)R-targeting peptide CP04 ([(177)Lu]Lu-1b). [(177)Lu]Lu-1b-4b showed high chemical purity (HPLC >/= 94%), low Log D(7.4) (-4.09 to -4.55) with strong binding affinity to CCK(2)R (K(D) 0.097-1.61 nM), and relatively high protein binding (55.6-80.2%) and internalization (40-67%). Biodistribution studies of the novel (177)Lu-labeled peptides in tumors (AR42J and A431-CCK(2)R) showed uptake one- to eight-fold greater than the reference compound CP04 at 1, 24, and 48 h. Rapid clearance and high tumor uptake and retention were established for [(177)Lu]Lu-2b-4b, making these compounds excellent candidates for theranostic applications against CCK(2)R-expressing tumors.
- Publisher
- ACS Publications
- Keywords
- *Receptor, Cholecystokinin B/metabolism; Precision Medicine; Tissue Distribution; Cell Line, Tumor; Peptides/chemistry; *Neoplasms/drug therapy
- Department(s)
- Cancer Imaging; Laboratory Research
- PubMed ID
- 37493526
- Publisher's Version
- https://doi.org/10.1021/acs.jmedchem.3c00377
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-10-25 06:30:03
Last Modified: 2024-07-09 05:18:04