First-in-human study of novel integrin receptor PET tracer
The first PET imaging study of its kind to show the viability of tumor angiogenesis imaging in humans with investigational Ga-68 NODAGA-Theranost has been conducted by researchers from the Theranostics Center for Molecular Radiotherapy and Molecular Imaging in Bad Berka, Germany, and other institutions including the National Cancer Institute and Advanced Imaging projects based in Boca Raton, Fla. Molecular Imaging has obtained an exclusive sneak-peek at the study.
Richard P. Baum, MD, PhD, chairman and clinical director for the Theranostics Center at Zentralklinik Bad Berka, and colleagues evaluated the tracer for its ability to find new vasculature developing in and around tumors. Ga-68 NODAGA-Theranost is able to plug into angiogenesis by binding to avb3 integrin receptors.
“Integrins play a vital role in angiogenesis, leukocyte function and tumor growth and are potential targets for therapeutic agents, demonstrating an anti-proliferative effect on tumor growth and the selective inhibition of endothelial αvb3 integrin; also, they have been shown to increase the effectiveness of combination regimens such as chemotherapy and radiochemotherapy,” wrote Baum et al. “The αvb3 integrin is significantly over-expressed in certain types of tumor cells and in almost all tumor vasculature.”
In this study, the authors present the feasibility of integrin-receptor peptidomimetic PET imaging for non small cell lung cancer (NSCLC) and breast cancer patients.
“Integrins play a vital role in angiogenesis, leukocyte function and tumor growth and are potential targets for therapeutic agents, demonstrating an anti-proliferative effect on tumor growth and the selective inhibition of endothelial αvb3 integrin; also, they have been shown to increase the effectiveness of combination regimens such as chemotherapy and radiochemotherapy,” wrote Baum et al. “The αvb3 integrin is significantly over-expressed in certain types of tumor cells and in almost all tumor vasculature.”
The researchers imaged two patients with PET/CT and Ga-68 NODAGA-Theranost. One subject was a 61-year-old male with neuroendocrine neoplasm of the lung and the other a 28-year-old female with breast cancer and metastases to the liver. Scans were obtained 60 minutes following injection of the tracer.
Results of the study showed that the investigational Ga-68 conjugated tracer was able to detect 25 integrin avb3 positive tumors compared to the 12 caught with F-18 FDG PET/CT. Some tumors showed no uptake of Ga-68 NODAGA-Theranost, indicating a lack of neovasculature.
This kind of specificity could inform researchers and clinicians about the potential grade and aggressiveness of tumors, as well as therapeutic response for patients in treatment.
“To the best of our knowledge, this is the first report on the ability of Ga-68 NODAGA-Theranost to detect solid tumors in humans, establish the absence of neovascularization and predict anti-tumor effect,” the researchers wrote.
Ga-68 NODAGA-Theranost is not yet approved by the FDA. More clinical trials in larger patient populations will need to be conducted before this technique could be translated to general clinical practice.