Small cell lung cancer (SCLC) and neuroendocrine prostate cancer (NEPC) are types of neuroendocrine cancers, which develop in hormone-producing cells. SCLC is known for its rapid spread to other regions and lymph nodes in the chest. The five-year survival rate stands at 18% when it is diagnosed after it has spread beyond the lungs. NEPC, while rare, is highly lethal and lacks effective standard treatments. It may appear as a new cancer, referred to as “de novo,” or develop from more common prostate adenocarcinoma, often due to the effects of treatments like hormone therapy or chemotherapy. NEPCs are challenging to detect and usually require biopsies for diagnosis, posing an increasing challenge in prostate cancer management. However Now, a new imaging technology has been shown to enhance the detection of metastatic SCLC and NEPC, which conventional imaging methods might miss.

This advanced imaging method, developed at Memorial Sloan Kettering Cancer Center (MSK, New York, NY, USA), utilizes a radioactive tracer designed to bind to a specific cancer cell ligand known as DLL3, enhancing the visibility of these cells on PET scans. DLL3 is predominantly expressed in aggressive forms of SCLC and NEPC, aiding in the identification of patients who could benefit from new DLL3-targeting drugs currently under clinical evaluation. Furthermore, researchers are exploring ways to couple these drugs with radioactive materials to create a targeted treatment that spares healthy cells while eliminating cancer cells.

Named [89Zr]Zr-DFO-SC16.56, this imaging agent is a significant advancement in the field of theranostics, which combines diagnostic and therapeutic capabilities in a single agent. The imaging agent is injected into the body by a nuclear medicine physician, followed by its absorption by cancer cells that express DLL3. This process allows physicians to use PET scans to determine the extent of the cancer and guide treatment decisions. This agent not only detects minute metastases to the brain but may also be applicable to other cancers like thyroid cancer and neuroblastoma. Initial results from a pilot study published in The Lancet Oncology have shown that [89Zr]Zr-DFO-SC16.56 reliably identifies cancer cells with DLL3 in 18 patients, without raising safety issues. Plans are underway to further evaluate this agent in a larger cohort, with MSK receiving multiple grants to advance and validate this DLL3-focused technology.

“DLL3-targeting technology could be the next generation of theranostics, guiding new treatments for patients with small cell lung cancer or neuroendocrine prostate cancers who otherwise would have run out of options,” said MSK radiochemist Jason S. Lewis, PhD. 

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