¹⁷⁷Lu-Labeled Heterodimeric Agent with High Stability Targeting Neovascularization for Tumor Radioligand Therapy

Area of Science:

• Nuclear medicine
• Oncology
• Radiopharmaceutical chemistry

Background:

• Radiopharmaceutical theranostics show promise for cancer diagnosis and treatment.
• Suboptimal tumor uptake and retention limit current radiopharmaceuticals.
• Previous precursor L6 exhibited instability under alkaline conditions due to NGR to iso-DGR rearrangement.

Purpose of the Study:

• To synthesize and evaluate a novel, more stable radiopharmaceutical precursor, XH02.
• To assess the in vitro and in vivo properties of radiolabeled XH02.
• To investigate the potential of XH02 for enhanced tumor targeting and therapeutic efficacy.

Main Methods:

• Synthesis and radiolabeling of the novel precursor XH02.
• In vitro and in vivo evaluation in BxPC-3 xenograft mouse models.
• Utilized PET/CT and SPECT/CT imaging for biodistribution and tumor accumulation assessment.

Main Results:

• XH02 demonstrated striking accumulation and retention within tumors.
• Radiolabeled XH02 showed exceptional tumor growth inhibition in BxPC-3 xenografts after two administration cycles.
• The agent exhibited minimal observed side effects in the preclinical study.

Conclusions:

• XH02 represents a promising advancement in radiopharmaceutical theranostics.
• The enhanced tumor uptake and retention of XH02 offer potential for improved cancer treatment.
• Further clinical translation and investigation of XH02 are warranted.