- Researchers have identified a new radioactive agent called CB-2PA-NT as a promising candidate for a combined therapeutic-diagnostic theranostic strategy.
- The substance targets neurotensin receptors found in a variety of cancers and exhibits high uptake and retention within tumors while maintaining distinct differentiation from surrounding tissue.
- With regulatory approval pending, the researchers hope to conduct human imaging studies with CB-2PA-NT in the near future, which could have implications for personalized medicine for cancer patients. may give.
The University of North Carolina and the University of Wisconsin have teamed up to develop a new anticancer drug candidate called CB-2PA-NT that has broad applications.
This study lays the groundwork for future studies using CB-2PA-NT for human imaging, although regulatory approval is still required to initiate these studies.
New research results presented at the Annual Meeting of the Society for Nuclear Medicine and Molecular Imaging (SNMMI 2023) position CB-2PA-NT as a promising candidate for innovative therapeutics.
Finding the right treatment requires a correct diagnosis. Accurate diagnosis is even more important in the era of personalized medicine, where treatments can be customized according to individual biomarkers.
This is especially true in the field of oncology, where obtaining an accurate diagnosis is extremely important.
Theranostics presents a powerful strategy in the fight against cancer that combines two key elements. This involves identifying cancer cells throughout the body and using special radiation to remove the cancer cells.
Positron Emission Tomography (PET) is used to pinpoint cancer, followed by drug administration to eradicate the cancer. Therapeutic precision of Theranostics greatly reduces the chance of damaging adjacent healthy tissue.
CB-2PA-NT has great potential to advance the field of precision medicine by specifically targeting neurotensin receptors (NTSR) found in various types of cancer.
NTSR is a receptor that is found at high levels on various types of cancer including lung, colorectal, breast, pancreatic and prostate cancer.
Scientists have worked to create radioactive substances that can specifically bind to one of these receptors, NTSR1.
However, previous attempts to produce these substances have had limited success in how well they are taken up and retained by tumors.
Xinrui Ma, a postdoctoral fellow at the University of North Carolina at Chapel Hill and one of the study authors, explained the key findings: medical news today.
“this [study] The abstract reports on new therapeutics that target neurotensin receptor 1 (NTSR1) and their applications in cancer imaging and therapy,” Ma explained.
“So far, several groups, including ours, have attempted to optimize NTSR1-related drugs. In fact, we have been working on this goal since 2012. , high liver uptake, and some drug agonism,” she noted. ligand and/or rapid washout. “
“Based on our previous research and experience, we found that the cross-linked propylamine moiety can significantly improve tumor uptake and retention,” added Ma.
“Compared to peptide-based ligands, tumor uptake was increased ten-fold while still being maintained.[ing] high contrast. More importantly, high uptake was maintained at 24 hours and he at 48 hours after injection,” the researchers emphasized.
“The significant improvement in tumor uptake and retention presents a unique opportunity to develop therapeutics for patient management. We have established collaborations to explore the therapeutic potential of these novel agents in various cancer types, including lung, colorectal and PSMA-negative prostate cancer.”
– Shinrui Ma
In their study, the researchers examined various NTSR1 antagonists to determine which one was the most effective for both imaging and therapeutic purposes.
Next, experiments were conducted to label these substances with radioactive markers. Using a technique called Western blotting, they confirmed that the NTSR1 receptor is indeed present in lung cancer cells (H1299 cells).
The researchers also tested the substance’s stability in both laboratory tests and live animals, and evaluated how well the substance binds to lung cancer cells in test-tube experiments.
Finally, they combined PET and CT imaging in small animals to study how substances are distributed throughout the body.
The results showed that the NTSR1 receptor was highly expressed in H1299 lung cancer cells, as confirmed by western blot. Among the NTSR1 antagonists, a substance called CB-2PA-NT showed strong binding ability to H1299 lung cancer cells.
Imaging studies in small animals confirmed that CB-2PA-NT was extensively taken up by tumors, exhibited a clear contrast between the tumor and surrounding tissue, and persisted for a long time within the tumor.
CB-2PA-NT stood out as the most promising substance when compared to other NTSR1 antagonists and was selected for further study.
If this therapeutic approach is successful, it may provide an effective method to accurately detect the presence of NTSR1 in various cancer types by imaging.
This could be of value for diagnosis, patient screening, and monitoring treatment progress. In addition, it may also serve as a radioactive material for therapeutic purposes.
Dr. Tejasab Sefrawat, a Yale University resident who was not involved in the project, said: MNT “Therapeutics is a nascent field for cancer diagnosis and treatment. It holds a lot of interest and potential. [the] Development of the whole field. This study has been successfully conducted and it is encouraging to note the promising preclinical results. ”
“Although the authors have already demonstrated results in animal models, [a] It is necessary to confirm the application to humans. Due to the high inter-species variability in such studies, we should all look forward to future human studies planned by the authors. “
Dr. Tejasab Sefrawat
“This study is important because it has the potential to provide personalized care to cancer patients,” said Professor Ma.
“From a disease perspective, NTSR was found to be overexpressed in prostate cancer, especially in PSMA-negative prostate cancer tissue,” she told us.
“This suggests that NTSR1-targeted theranostics may be an approach to prostate cancer in populations where PSMA-based strategies are unacceptable. , and may also be used in many lung, colorectal, breast and pancreatic cancers.”
– Shinrui Ma
“A wide range of patients may benefit from newly developed drugs,” Ma noted.
More work is needed, and the researchers are now awaiting regulatory approval to conduct the first human imaging study with CB-2PA-NT.
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