Small animal PET imaging with the 68Ga-labeled pH (low) insertion peptide-like peptide YJL-4 in a triple-negative breast cancer mouse model

• Main Authors: YueHua Chen (Author), ShuangShuang Song (Author), YanQin Sun (Author), FengYu Wu (Author), GuangJie Yang (Author), ZhenGuang Wang (Author), MingMing Yu (Author)
• Format: Book
• Published: SpringerOpen, 2024-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/s41181-024-00267-x; 2365-421X
• Keywords: Triple-negative breast cancer; Tumor microenvironment; pH (low) insertion peptides; 68Ga; Small animal PET/CT; Molecular imaging; Medical physics. Medical radiology. Nuclear medicine; R895-920; Therapeutics. Pharmacology; RM1-950
• Source: EJNMMI Radiopharmacy and Chemistry, Vol 9, Iss 1, Pp 1-14 (2024)

Abstract Background The aim of this study was to prepare a novel 68Ga-labeled pH (low) insertion peptide (pHLIP)-like peptide, YJL-4, and determine its value for the early diagnosis of triple-negative breast cancer (TNBC) via in vivo imaging of tumor-bearing nude mice. The novel peptide YJL-4 was designed using a template-assisted method and synthesized by solid-phase peptide synthesis. After modification with the chelator 1,4,7‑triazacyclononane-N,N',N"-triacetic acid (NOTA), the peptide was labeled with 68Ga. Then, the biodistribution of 68Ga-YJL-4 in tumor-bearing nude mice was investigated, and the mice were imaged by small animal positron emission tomography (PET). Results The radiochemical yield and radiochemical purity of 68Ga-YJL-4 were 89.5 ± 0.16% and 97.95 ± 0.06%, respectively. The biodistribution of 68Ga-YJL-4 in tumors (5.94 ± 1.27% ID/g, 6.72 ± 1.69% ID/g and 4.54 ± 0.58% ID/g at 1, 2 and 4 h after injection, respectively) was significantly greater than that of the control peptide in tumors at the corresponding time points (P < 0.01). Of the measured off-target organs, 68Ga-YJL-4 was highly distributed in the liver and blood. The small animal PET imaging results were consistent with the biodistribution results. The tumors were visualized by PET at 2 and 4 h after the injection of 68Ga-YJL-4. No tumors were observed in the control group. Conclusions The novel pHLIP family peptide YJL-4 can adopt an α-helical structure for easy insertion into the cell membrane in an acidic environment. 68Ga-YJL-4 was produced in high radiochemical yield with good stability and can target TNBC tissue. Moreover, the strong concentration of radioactive 68Ga-YJL-4 in the abdomen does not hinder the imaging of early TNBC.