Novel Radiotracer Identifies Critical Cancer Biomarker, Opens Door to New Therapeutic Target for Solid Tumors

Reston, VA (December 17, 2024)—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.

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,” said 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.”

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,” noted Wei. “This is the cornerstone of precision medicine: selecting the right treatment for the right patient.”

Figure 5. [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.

The authors of “Immuno-PET/CT Imaging of Trop2 with [¹⁸F]AlF-RESCA-T4 Differentiates Lung Cancer from Inflammation” include Wei Huang, You Zhang, Shuxian An, Xinbing Pan, Xinyuam Zhou, Hongda Shao, Gang Huaung, Jianjun Liu, and Weijun Wei, Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China; Min Cao, Department of Thoracic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Yanfei Wu, Yihui Guan, and Fang Xie, Department of Nuclear Medicine and PET Center, Huashan Hospital, Fudan University, Shanghai, China; and Fabrizia Gelardi and Arturo Chiti, Università Vita-Salute San Raffaele, Milan, Italy, and Nuclear Medicine Department, IRCCS San Raffaele, Milano, Italy.

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