Biotechnology

New theranostic agents target various types of cancer

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Chicago, Illinois (Embargo until 3:55 p.m. CDT, Tuesday, June 27, 2023)—A recently discovered radionuclide-based agent (CB-2PA-NT) has been shown to have high tumor uptake, sustained tumor retention, and high contrast in preclinical models, making it a prime candidate for novel theranostics approaches. Targeting the neurotensin receptors (NTSRs) present in a variety of cancer types, CB-2PA-NT has the potential to significantly expand the scope of precision medicine. This research was presented at the 2023 Society of Nuclear Medicine and Molecular Imaging Annual Meeting.

NTSR is overexpressed in a variety of cancer types, including lung, colorectal, breast, pancreatic, and prostate cancers. Recently, several attempts have been made to synthesize radiometal-labeled agents targeting the NTSR1 receptor. However, most of these attempts showed only moderate tumor uptake and retention.

“Based on previous research and experience, my colleagues and I found that cross-linked polyamine moieties can greatly enhance tumor uptake and maintain high contrast,” said Xinrui Ma, MPH, a doctoral student at the University of North Carolina at Chapel Hill. North Carolina. “In this study we tested a range of NTSR1 antagonists to see which would be most useful for imaging and therapeutic applications.”

A series of NTSR1 antagonists were synthesized with variable length propylamine linkers and different chelator (CB, NOTA, and DOTA), and radiolabeling reactions were carried out. Western blot was used to determine NTSR expression in a human lung cancer cell line (H1299). The in vitro and in vivo stability of the antagonist and its binding affinity to lung cancer cells were also assessed. Finally, small animal PET/CT imaging was used to evaluate the biodistribution properties of the agent.

NTSR1 was confirmed to have high expression in H1299 cells by western blot. CB-2PA-NT antagonists exhibit good binding affinity to H1299 cells, and small mammalian imaging confirmed prominent tumor uptake, high tumor-to-background contrast, and prolonged tumor retention. After comparison with other NTSR1 antagonists, CB-2PA-NT was identified as the leading agent for further evaluation.

“The success of this theranostic approach has the potential to provide accurate imaging-based methods to efficiently detect NTSR1 expression in various types of cancer for diagnosis, patient screening, and treatment monitoring, as well as radionuclide-based agents for therapy. This will ultimately lead to more personalized medicine for cancer patients,” said Ma.

To further explore the potential of this theranostic agent for patient management, University of North Carolina researchers have collaborated with the University of Wisconsin, and the first human imaging with CB-2PA-NT is expected to begin in the near future following regulatory approval. .

Abstract 382. “Synthesis and evaluation of 64Cu-labeled neurotensin receptor antagonists for theranostic applications.” Xinrui Ma, Muyun Xu, German Fonseca Cabrera, Zhanhong Wu, and Zibo Li, University of North Carolina, Chapel Hill, North Carolina; and Tao Zhang, Nanjing Medical University, Nanjing, China.

Link to Session

###

All abstracts of the 2023 SNMMI Annual Meeting can be found online.

About Society of Nuclear Medicine and Molecular Imaging
The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and medical organization dedicated to advancing nuclear medicine and molecular imaging—critical elements of precision medicine that allow diagnosis and treatment to be tailored to the individual patient to achieve the best outcome. results.

Representative PET images of the three main compounds in H1299 tumor mice at 24 h post injection at 10% ID/g scale.

Credit: Image courtesy X Ma et al., UNC, Chapel Hill.

Chicago, Illinois (Embargo until 3:55 p.m. CDT, Tuesday, June 27, 2023)—A recently discovered radionuclide-based agent (CB-2PA-NT) has been shown to have high tumor uptake, sustained tumor retention, and high contrast in preclinical models, making it a prime candidate for novel theranostics approaches. Targeting the neurotensin receptors (NTSRs) present in a variety of cancer types, CB-2PA-NT has the potential to significantly expand the scope of precision medicine. The research was presented at the Society for Nuclear Medicine and Molecular Imaging 2023 Annual Meeting.

NTSR is overexpressed in a variety of cancer types, including lung, colorectal, breast, pancreatic, and prostate cancers. Recently, several attempts have been made to synthesize radiometal-labeled agents targeting the NTSR1 receptor. However, most of these attempts showed only moderate tumor uptake and retention.

“Based on previous research and experience, my colleagues and I found that cross-linked polyamine moieties can greatly enhance tumor uptake and maintain high contrast,” said Xinrui Ma, MPH, a doctoral student at the University of North Carolina at Chapel Hill. North Carolina. “In this study we tested a range of NTSR1 antagonists to see which would be most useful for imaging and therapeutic applications.”

A series of NTSR1 antagonists were synthesized with variable length propylamine linkers and different chelator (CB, NOTA, and DOTA), and radiolabeling reactions were carried out. Western blot was used to determine NTSR expression in a human lung cancer cell line (H1299). The in vitro and in vivo stability of the antagonist and its binding affinity to lung cancer cells were also assessed. Finally, small animal PET/CT imaging was used to evaluate the biodistribution properties of the agent.

NTSR1 was confirmed to have high expression in H1299 cells by western blot. CB-2PA-NT antagonists exhibit good binding affinity to H1299 cells, and small mammalian imaging confirmed prominent tumor uptake, high tumor-to-background contrast, and prolonged tumor retention. After comparison with other NTSR1 antagonists, CB-2PA-NT was identified as the leading agent for further evaluation.

“The success of this theranostic approach has the potential to provide accurate imaging-based methods to efficiently detect NTSR1 expression in various types of cancer for diagnosis, patient screening, and treatment monitoring, as well as radionuclide-based agents for therapy. This will ultimately lead to more personalized medicine for cancer patients,” said Ma.

To further explore the potential of this theranostic agent for patient management, University of North Carolina researchers have collaborated with the University of Wisconsin, and the first human imaging with CB-2PA-NT is expected to begin in the near future following regulatory approval. .

Abstract 382. “Synthesis and evaluation of 64Cu-labeled neurotensin receptor antagonists for theranostic applications.” Xinrui Ma, Muyun Xu, German Fonseca Cabrera, Zhanhong Wu, and Zibo Li, University of North Carolina, Chapel Hill, North Carolina; and Tao Zhang, Nanjing Medical University, Nanjing, China.

Link to Session

###

All abstracts of the 2023 SNMMI Annual Meeting can be found online.

About Society of Nuclear Medicine and Molecular Imaging
The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and medical organization dedicated to advancing nuclear medicine and molecular imaging—critical elements of precision medicine that allow diagnosis and treatment to be tailored to the individual patient to achieve the best outcome. results.

SNMMI members set standards for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings, and leading advocacy on key issues affecting molecular imaging and therapy research and practice. For more information, visit www.snmmi.org.


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