Summary: A new molecular imaging agent, 18F-AlF-RESCA-T4, enables precise visualization of the Trop2 biomarker in various cancers, aiding diagnosis, personalized treatment planning, and differentiation of cancer from inflammation, as demonstrated in preclinical and pilot clinical trials.

Key Takeaways

  • Trop2 Biomarker Significance: Trop2 is a critical biomarker involved in various cancers, including triple-negative breast cancer, colorectal cancer, and non–small cell lung cancer, making it a key target for diagnostic and therapeutic advancements.
  • Radiotracer Development: Two novel Trop2-targeted radiotracers, 18F-AlF-RESCA-T4 and 18F-AlF-RESCA-RT4, were developed, with 18F-AlF-RESCA-T4 demonstrating superior performance and lower kidney accumulation in preclinical and pilot clinical trials.
  • Precision Medicine Potential: PET/CT imaging with 18F-AlF-RESCA-T4 enhances the ability to visualize Trop2 expression, aiding in identifying Trop2-positive tumors and advancing personalized cancer treatment strategies.

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A new molecular imaging agent can accurately identify a crucial biomarker found among many different types of cancer. Precise visualization of the trophoblast cell surface antigen 2 (Trop2) biomarker can provide physicians with valuable insights for diagnosis, development of a personalized treatment plan, and response assessment. This research was published in the December issue of The Journal of Nuclear Medicine. 

Next-Gen Cancer Diagnostics

Trop2 has garnered interest among cancer researchers recently due to the significant role it plays in cell self-renewal, proliferation, transformation, and organ development. It is commonly found in triple-negative breast cancer, colorectal cancer, gastric carcinoma, pancreatic cancer, and non–small cell lung cancer, among other solid tumors.

“Trop2 is an emerging biomarker for developing next-generation diagnostic and therapeutic agents for solid tumors and has the potential to be a game-changer for cancer treatment,” says Weijun Wei, MD, PhD, associate research professor in the department of nuclear medicine at Renji Hospital School of Medicine at Shanghai Jiao Tong University in China. “However, efficiently visualizing Trop2 expression and selecting patients who might benefit from Trop2-targeted therapies is a clinical challenge.”

Trop2 Imaging Benefits

To further the research on Trop2, Wei and colleagues developed two novel Trop2-targeted radiotracers: 18F-AlF-RESCA-T4 and 18F-AlF-RESCA-RT4. Preclinical imaging and blocking studies were performed on tumor-bearing mice to determine safety and efficacy. A pilot clinical trial including three patients with suspected lung cancer was also conducted. This trial included a head-to-head comparison of PET/CT imaging with 18F-AlF-RESCA-T4, 18F-AlF-RESCA-RT4, and a previously developed radiotracer, 68Ga-NOTA-T4.

Prominent tumor uptake was observed with both 18F-AlF-RESCA-T4 and 18F-AlF-RESCA-RT4, however the latter showed substantially reduced kidney accumulation. In the clinical trial’s head-to-head comparison, 18F-AlF-RESCA-T4 performed best. Initial 18F-AlF-RESCA-T4 immuno-PET/CT imaging demonstrated the ability to visualize Trop2 expression in suspected lung cancer patients; it was also able to differentiate lung inflammation, such as tuberculosis, from cancer.

“PET imaging with 18F-AlF-RESCA-T4 will allow physicians to identify patients with Trop2-positive tumors so they can receive Trop2-targeted treatments,” says Wei. “This is the cornerstone of precision medicine: selecting the right treatment for the right patient.”

Featured image: [18F]AlF-RESCA-T4 immuno-PET/CT imaging of patient with primary lung cancer. (A–C) Maximum-intensity projection (A) and fusion images (B and C) of [18F]AlF-RESCA-T4 immuno-PET/CT. Yellow arrowhead indicates presence of left hilar occupancy and lymph node in fusion image. Blue arrowhead indicates presence of distal lung atelectasis. Physiologic uptake of [18F]AlF-RESCA-T4 by normal organs and tissues is indicated by red arrows. (D) Histologic examination of resected left hilar mass showed intense Trop2 staining. IHC = immunohistochemistry.