Advancing Radiotheranostics at Duke Through Prostate, Neuroendocrine Cancer Research
Published
Radiotheranostics is a rapidly evolving field that combines targeted imaging and therapy using radiolabeled molecules. At Duke Cancer Institute, researchers are exploring new opportunities for this therapeutic approach in prostate and neuroendocrine cancer care through strategic clinical trials and interdisciplinary collaboration.
Neuroendocrine Cancer: Building on a Legacy of Innovation
Michael Morse, MD, medical oncologist with the DCI Gastrointestinal Cancer disease program, has had a longstanding collaboration with the Division of Nuclear Medicine and Radiotheranostics, particularly with nuclear medicine specialist Terence Wong, MD, PhD. Morse, Wong, and their teams have worked together integrating imaging and radiopharmaceutical treatment of neuroendocrine tumors (NETs).
Duke was one of the early leaders in this research through work with I-131 MIBG, a radiolabeled compound previously used for treating neuroendocrine tumors, pheochromocytomas, and paragangliomas.
More recently, Duke participated in the NETTER-1 trial which led to the FDA approval of Lu177-dotatate (Lutathera®) for gastroenteropancreatic NETs. The institution played a key role in subsequent compassionate use programs and has since become one of the leading centers in the Southeast for Lutathera® administration.
More recently, Duke has been a top U.S. recruiter for the COMPOSE trial, a study comparing ITM-11, a novel lutetium-based therapy, to standard for patients with intermediate and high-grade neuroendocrine tumors.
Morse also highlighted Duke’s opening of the BELU-RE trial, a national study evaluating Lutathera® in patients with pulmonary NETs, a group currently excluded from the FDA-approved indication of this drug. He said the growing interest in radioligands based on alpha emitters like Actinium-225 and Lead-212 offers higher energy and more potent DNA damage than traditional beta emitters.
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“Duke’s involvement in radiotheranostics clinical research has given our patients early access to these drugs which are assuming an increasingly important role in neuroendocrine tumor therapy.”
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Michael Morse
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Medical Oncologist, DCI Gastrointestinal Cancer disease program
Prostate Cancer: Expanding the Boundaries of Radioligand Therapy
In the prostate cancer space, Daniel George, MD, co-chair of the DCI Center for Prostate and Urologic Cancers, is leading efforts to expand the use of radioligand therapies beyond their current FDA-approved indications.
“For men with castration-resistant metastatic prostate cancer, the clock is ticking,” George said. “Their average survivals are around three years. Radioligand therapies deliver lethal radiation specifically to tumors, which can improve patient outcomes.”
Vipivotide tetraxetan (PLUVICTO®) is currently approved for treatment of patients with metastatic castration-resistant prostate cancer, but the institution is exploring ways to enhance its efficacy and broaden its application. One strategy involves combining PLUVICTO® with DNA repair inhibitors, aiming to prevent cancer cells from recovering from radiation-induced damage.
Another promising avenue is the use of Actinium-225, an alpha emitter that delivers significantly more radiation per molecule than the beta emitting lutetium-177, potentially improving cell kill rates with greater precision.
Researchers at Duke are also investigating alternative targets like KLK2, a prostate cancer surface bound molecule like PSA, through trials that combine KLK2-targeted radioligands with chemotherapy or use them in post- PLUVICTO® settings. These studies aim to address unmet needs in patients with resistant or heavily pretreated cancers.
The institution is also preparing to launch trials in high-risk localized prostate cancer, administering radioligand therapy prior to prostatectomy. This approach could offer curative potential by eradicating microscopic disease beyond the surgical field, potentially reducing the need for hormonal therapy.
Additionally, Duke investigators will explore radiotheranostics in kidney cancer, targeting CA-9 with novel imaging and therapeutic agents currently under FDA review.
A Vision for the Future
Morse and George emphasized the importance of adaptive and personalized approaches to radiotheranostics. As trials evolve, research teams will look at refining dosing strategies, tailoring treatments based on tumor response, and leveraging advanced imaging to guide therapy decisions.
“These studies are more complicated and require a lot of coordination,” George said. “They require specialized infrastructure and expertise only available at centers of excellence like Duke.”
For many people with lung cancer, the disease doesn’t stay confined to the lungs. Up to half of patients with non-small cell lung cancer, and as many as 80 percent of patients with small cell lung cancer, develop brain metastases throughout the course of their illness. These diagnoses can significantly affect quality of life, treatment options, and long-term outcomes.At Duke Cancer Institute (DCI), Laura Alder, MD, deputy director of medical oncology for the Duke Center for Brain and Spine Metastasis, is working to change how patients with brain metastases are represented in clinical research and, ultimately, how they are treated.Alder’s clinical and research career centers on two closely related priorities: lung cancer and brain metastases. After completing her fellowship at Duke, she joined the faculty and became deeply involved in multidisciplinary efforts to improve care for patients whose cancer has spread to the brain or spine.“Brain metastases have a huge impact on a patient’s trajectory,” Alder said. “They affect quality of life, treatment decisions, and outcomes in very meaningful ways.”Clinical trials often represent the most promising treatment option for patients with advanced cancer, offering access to therapies that are not yet widely available. However, Alder notes that trial eligibility criteria have traditionally been narrow.“There’s been a longstanding concern that patients with brain metastases wouldn’t do well on clinical trials or could confound the results,” Alder said. “As a result, many trials exclude these patients entirely.”To address this gap, Alder collaborated with a multidisciplinary group of researchers on a publication focused on improving clinical trial inclusion for patients with lung cancer and brain metastases. The work, published recently in Lung Cancer, builds on decades of research led by Paul Sperduto, MD, PhD, adjunct professor in the Duke Department of Radiation Oncology, who developed the Graded Prognostic Assessment (GPA).The GPA is a validated tool used to estimate survival in patients with brain metastases by accounting for factors such as age, performance status, disease burden, and tumor biology. For non-small cell lung cancer, the tool incorporates modern biomarkers, including genetic driver mutations, which can influence response to targeted immunotherapies.Paired with the eligibility quotient (EQ), which helps estimate conditional survival, these tools paint a more accurate and individualized picture of prognosis, one that challenges outdated assumptions.“What we see is that many of these patients actually have very good overall survival,” Alder said. “Our therapies are better, more precise, and more effective than ever before.”Alder said advances in imaging, MRI surveillance, and radiation techniques, such as stereotactic radiosurgery (SRS), also make it possible to closely monitor and manage brain metastases during treatment. These innovations further support the safe inclusion of these patients in trials.At Duke, efforts to improve clinical trial inclusivity extend beyond a single publication. Through the Duke Center for Brain and Spine Metastasis, clinicians and researchers regularly collaborate with pharmaceutical partners, advocate at national conferences, and engage in ongoing dialogue with industry leaders.“This has been a mission for many of us for years,” Alder said. “At every meeting, every podium, we’re making the case that these patients need to be included because that’s where the unmet need is.”Encouragingly, progress is being made. National organizations such as the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO), along with the U.S. Food and Drug Administration (FDA), have increasingly emphasized the importance of broader eligibility criteria in cancer trials.Alder hopes the framework outlined in the publication will be used prospectively in future trials, helping demonstrate that inclusion of patients with brain metastases is both safe and beneficial.“Our patients are living longer than ever before,” she says. “They deserve clinical trials that reflect the reality of their disease and give us the data we need to keep making progress.”
For many people with lung cancer, the disease doesn’t stay confined to the lungs. Up to half of patients with non-small cell lung cancer, and as many as 80 percent of patients with small cell lung cancer, develop brain metastases throughout the course of their illness. These diagnoses can significantly affect quality of life, treatment options, and long-term outcomes.At Duke Cancer Institute (DCI), Laura Alder, MD, deputy director of medical oncology for the Duke Center for Brain and Spine Metastasis, is working to change how patients with brain metastases are represented in clinical research and, ultimately, how they are treated.Alder’s clinical and research career centers on two closely related priorities: lung cancer and brain metastases. After completing her fellowship at Duke, she joined the faculty and became deeply involved in multidisciplinary efforts to improve care for patients whose cancer has spread to the brain or spine.“Brain metastases have a huge impact on a patient’s trajectory,” Alder said. “They affect quality of life, treatment decisions, and outcomes in very meaningful ways.”Clinical trials often represent the most promising treatment option for patients with advanced cancer, offering access to therapies that are not yet widely available. However, Alder notes that trial eligibility criteria have traditionally been narrow.“There’s been a longstanding concern that patients with brain metastases wouldn’t do well on clinical trials or could confound the results,” Alder said. “As a result, many trials exclude these patients entirely.”To address this gap, Alder collaborated with a multidisciplinary group of researchers on a publication focused on improving clinical trial inclusion for patients with lung cancer and brain metastases. The work, published recently in Lung Cancer, builds on decades of research led by Paul Sperduto, MD, PhD, adjunct professor in the Duke Department of Radiation Oncology, who developed the Graded Prognostic Assessment (GPA).The GPA is a validated tool used to estimate survival in patients with brain metastases by accounting for factors such as age, performance status, disease burden, and tumor biology. For non-small cell lung cancer, the tool incorporates modern biomarkers, including genetic driver mutations, which can influence response to targeted immunotherapies.Paired with the eligibility quotient (EQ), which helps estimate conditional survival, these tools paint a more accurate and individualized picture of prognosis, one that challenges outdated assumptions.“What we see is that many of these patients actually have very good overall survival,” Alder said. “Our therapies are better, more precise, and more effective than ever before.”Alder said advances in imaging, MRI surveillance, and radiation techniques, such as stereotactic radiosurgery (SRS), also make it possible to closely monitor and manage brain metastases during treatment. These innovations further support the safe inclusion of these patients in trials.At Duke, efforts to improve clinical trial inclusivity extend beyond a single publication. Through the Duke Center for Brain and Spine Metastasis, clinicians and researchers regularly collaborate with pharmaceutical partners, advocate at national conferences, and engage in ongoing dialogue with industry leaders.“This has been a mission for many of us for years,” Alder said. “At every meeting, every podium, we’re making the case that these patients need to be included because that’s where the unmet need is.”Encouragingly, progress is being made. National organizations such as the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO), along with the U.S. Food and Drug Administration (FDA), have increasingly emphasized the importance of broader eligibility criteria in cancer trials.Alder hopes the framework outlined in the publication will be used prospectively in future trials, helping demonstrate that inclusion of patients with brain metastases is both safe and beneficial.“Our patients are living longer than ever before,” she says. “They deserve clinical trials that reflect the reality of their disease and give us the data we need to keep making progress.”
