A novel solid phase synthesis of an estradiol derivative and preclinical evaluation for targeting estrogen-receptor positive breast cancer
Year: 2025
Type: article
Abstract: [ 18 F]-Fluoroestradiol, which is recently approved by the FDA, is a well-recognized estrogen receptor radiopharmaceutical in nuclear medicine to investigate both primary and metastatic breast cancers. This study introduces an innovative and effective method for synthesizing the DOTA-coupled estradiol derivative and evaluating its preclinical potential. 68 Ga/ 177 Lu-labeled estradiol derivative was evaluated in vitro for its stability in human plasma, and binding capacity was determined using the ER-positive MCF-7 breast cancer cell line. In vivo, biodistribution and tumor targeting were conducted in ER-positive MCF-7 tumor-bearing nude mice. DOTA conjugated estradiol was prepared conveniently using solid-phase synthesis, and its radiolabeling with both 68 Ga and 177 Lu resulted in the formation of one major product, with high labeling efficiency (≥ 90%). Also, a high stability of the radiotracer was found in human plasma. The radiolabeled estradiol derivative exhibited a nanomolar affinity (< 20 nM) specific to the MCF-7 cell line. In the MCF-7 tumor xenograft model, the radioestradiol derivative displayed fast clearance from the blood and excretion mainly by the renal system. A rapid accumulation of 3.79% IA/g was observed in the MCF-7 tumors at 1 h p.i., whereas a low to moderate retention of radioactivity was seen in the normal organs, including the heart, lungs, liver, stomach, spleen, intestines, and kidneys (< 5% ID/g). The receptor specificity of the radioestradiol was confirmed by the receptor-blocking assay. The rapid and efficient targeting of tumors, along with the favorable pharmacokinetics, emphasizes the potential of radioestradiol for targeting tumors. Additionally, PET imaging demonstrated good visualization of MCF-7 tumors in nude mice. Our results indicate that the 68 Ga/ 177 Lu-labeled estradiol derivative could serve as a promising radiopharmaceutical option for the effective targeting of MCF-7 tumors.
Source: Scientific Reports
Author: Subhani M. Okarvi
Institution: King Faisal Specialist Hospital & Research Centre
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W4413309277