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A new theranostatic agent may help improve the treatment of many forms of cancer. Image credit: Georgii Boronin/Getty Images.
  • Researchers have identified a new radioactive substance called CB-2PA-NT as a promising candidate for a theranostics strategy, combining therapy and diagnostics.
  • The substance, which targets neurotensin receptors found in various cancers, demonstrates high uptake and retention in tumors while maintaining a clear distinction from surrounding tissues.
  • With regulatory approval pending, researchers hope to conduct human imaging studies using CB-2PA-NT in the near future, which could impact personalized medicine for cancer patients.

The University of North Carolina and the University of Wisconsin have collaborated on developing a new anti-cancer drug candidate, called CB-2PA-NT, that may have a wide application.

This research lays the groundwork for future studies to use CB-2PA-NT in human imaging, although, regulatory approval is still needed before these studies can commence.

New study findings, presented at the Society of Nuclear Medicine and Molecular Imaging Annual Meeting (SNMMI 2023), position CB-2PA-NT as a promising candidate for an innovative theranostics strategy.

Finding the right treatment depends on the correct diagnosis. In the age of personalized medicine, where therapies can be customized according to a person’s specific biomarkers, an accurate diagnosis is even more essential.

This is particularly evident in the field of oncology, where the significance of obtaining a precise diagnosis is vital.

Theranostics presents a powerful strategy in the fight against cancer, combining two essential elements. It involves identifying cancer cells throughout the body and administering specialized radiation to eliminate them.

To pinpoint the cancer, positron emission tomography (PET) is employed, followed by the administration of medication to eradicate it. The remarkable precision of theranostics significantly lowers the likelihood of harming neighboring healthy tissues.

By specifically targeting neurotensin receptors (NTSRs) found in various types of cancer, CB-2PA-NT holds great potential for advancing the field of precision medicine.

NTSRs are receptors that are found at higher levels in different types of cancers such as lung, colorectal, breast, pancreatic, and prostate cancers.

Scientists have been working on creating radioactive substances that can specifically bind to NTSR1, one of these receptors.

However, previous attempts to make these substances have had limited success in terms of how well they are taken up and retained by tumors.

Xinrui Ma, a doctoral researcher at the University of North Carolina in Chapel Hill, and one of the study authors explained the key findings to Medical News Today.

“This [study] abstract reports a novel theranostic agent targeting neurotensin receptor 1 (NTSR1) and its application in cancer imaging and therapy,” Ma explained.

“Previously, several groups including us have tried to optimize NTSR1-related agents — in fact, we have been working on this target since 2012. However,” she noted, “challenges include low serum stability, high liver uptake, agonistic nature of some ligands and/or rapid washout.”

“Building on previous research and experience, we discovered that the cross-linked propylamine moiety can significantly improve tumor uptake and retention,” Ma added.

“Compared to the peptide-based ligand, the tumor uptake increased 10-fold while still maintain[ing] the high contrast. More importantly, the high uptake was maintained at 24 and 48 hours after injection,” highlighted the researcher.

“The greatly improved tumor uptake and retention provide us with a unique opportunity to develop theranostic agents for patient management. Indeed, we have established a close collaboration with Prof. Jonathan Engle’s group at U Wisconsin to explore the theranostic potential of these novel agents in various cancer types, including lung cancer, colorectal cancer, and PSMA-negative prostate cancer.”

– Xinrui Ma

In their study, the researchers examined a range of NTSR1 antagonists to determine which one would be most effective for both imaging and therapeutic purposes.

They then performed experiments to label these substances with a radioactive marker. They used a technique called western blot to confirm that the NTSR1 receptor was indeed present in the lung cancer cells (H1299 cells).

The researchers also tested the stability of the substances both in laboratory tests and in living animals and assessed how well the substances bound to the lung cancer cells in test tube experiments.

Finally, they used a combination of PET and CT imaging in small animals to study how the substances were distributed throughout the body.

The results showed that the NTSR1 receptor was highly expressed in the H1299 lung cancer cells, as confirmed by western blot. Among the NTSR1 antagonists, the substance called CB-2PA-NT showed a strong ability to bind to the H1299 lung cancer cells.

The imaging of small animals confirmed that CB-2PA-NT was taken up by the tumor in high amounts, showed a clear contrast between the tumor and the surrounding tissues, and remained in the tumor for a long time.

When compared to the other NTSR1 antagonists, CB-2PA-NT stood out as the most promising substance and was chosen for further investigation.

If this theranostic approach proves successful, it could offer an effective way to accurately detect the presence of NTSR1 in various types of cancer through imaging.

This would be valuable for diagnosis, patient screening, and monitoring the progress of treatment. Additionally, it could serve as a radioactive substance for therapy purposes.

Dr. Tejasav Sehrawat, a resident physician at Yale, who was not involved in the project, told MNT that “theranostics is a nascent field for diagnosing and treating cancers. There is a lot of interest and potential in [the] development of the field as a whole. This study is well performed and it’s encouraging to note the promising preclinical results.”

“While the authors have already proves their results in animal models, there is [a] need to confirm application in humans. There is high inter-species variability in such studies, so we should all look forward to results from the upcoming human studies that the authors have planned.”

Dr. Tejasav Sehrawat

Ma pointed out that “this research is significant because it may provide personalized medicine for cancer patients.”

“From a disease perspective, NTSR was found to be overexpressed in prostate cancer, particularly in PSMA-negative prostate cancer tissues,” she told us.

“This suggests that NTSR1-targeted theranostics could be an approach to prostate cancer in populations not amenable to PSMA-based strategies. NTSR-targeted theranostics could also be used for a large number of lung, colorectal, breast, and pancreatic cancers.”

– Xinrui Ma

“A broad spectrum of patients may benefit from the newly developed agents,” Ma pointed out.

More research is needed, and the researchers now await regulatory approval to conduct the first-ever human imaging studies using CB-2PA-NT.