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.

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.”