The Future of Radiopharm Trials with Dr. Gary Ulaner

It was wonderful to have a chance to sit down and speak with Dr. Gary Ulaner, MD, PhD. Dr. Ulaner currently serves as the James & Pamela Muzzy Endowed Chair of Molecular Imaging and Therapy (MIT) at the Hoag Family Cancer Institute and Professor of Radiology and Translational Genomics at the University of Southern California. His perspective on advancements in radiopharmaceutical clinical trials gives us a glimpse into what patients can expect in terms of treatment in the near future.

Transcript

Meet Dr. Ulaner:

I received my MD and PhD in cancer biology from Stanford University, then completed a residency in diagnostic radiology and a fellowship in nuclear medicine at the University of Southern California. I then started a junior faculty position at the Memorial Sloan Kettering Cancer Center (MSKCC), where I was a member of the breast and myeloma disease management teams.

Over 11 years at MSKCC, I rose from assistant to associate on the tenure track. Then in 2020, I was recruited to the Hoag Family Cancer Institute to establish a new molecular imaging and therapy clinic, the first in Orange County, California.

Over the last four years, our clinic has opened 28 clinical trials including phase 1, 2, 3, and 4 studies for patients with breast, prostate, neuroendocrine myeloma and pancreatic malignancies, as well as basket trials covering multiple solid tumors. These trials emphasize molecular imaging and molecularly targeted therapy with novel radiopharmaceuticals such as fluorine-18, gallium-68, copper-64, and copper-61 isotopes for imaging and lutetium-177, iodine-131, and actinium-225 isotopes for therapy.

At Hoag, we have accrued over 600 patients onto clinical trials in the last four years, including a 124-patient trial of fluoroestradiol PET imaging for patients with breast cancer, which was published in 2024 in JAMA [Network] Open; more than 20 patients accrued on trials of PSMA-targeted therapy with novel lutetium-177-labeled radiopharmaceuticals, and more than 30 patients accrued to a somatostatin receptor-targeted imaging and actinium-225 therapy trial for patients with metastatic breast cancer published in 2024 in Radiology.

We are currently one of the leading accruing sites on a trial of actinium-225-labeled radiopharmaceuticals for patients with metastatic prostate cancer, and we are the leading accruer of an imaging trial for favorable intermediate prostate cancer.

I’m particularly proud of our fluoroestradiol PET imaging trial published in JAMA Open, which could help expand use of fluoroestradiol PET for the care of patients with both ductal and lobular breast cancers.

Tell us about your collaboration with PSI.

I have a strong collaboration with PSI. Our first PSI trial was a trial of PSMA-targeted therapy with a novel lutetium-177 agent. We then opened trials of PSMA-targeted therapy with a novel actinium-225 agent.

We are opening a trial of fibroblast-activating protein, or FAP, targeted radioligand imaging and therapy in February of 2025, and I hope to accrue to that trial at a rate of about one patient per month or better.

Finally, we have been selected as a site for a trial of a novel lead-212-labeled therapy for patients with neuroendocrine tumors. This will be our first lead-212 trial, but our fifth alpha radiopharmaceutical trial overall.

I’m excited to see such success with opening alpha radiopharmaceutical therapy trials.

PSI CRO has been a remarkably professional organization to collaborate with. They’re clear, efficient, and accurate. I trust them and I’m confident in their work. They allow us to open trials quickly and are excellent with communicating issues that help our patients and the trial.

What is the outlook for radiopharmaceutical trials?

I only see continued growth for the field of molecular imaging and therapy as novel targets, better binding agents, and more efficacious radioisotopes are discovered. The available radiopharmacy will certainly expand. Novel targets such as FAP, CA9, and gastrin-releasing peptide receptor are already demonstrating utility. New radioisotopes, such as copper-61 for imaging as well as lead-212 and astatine-211 for therapy, will greatly expand opportunities to develop effective radiopharmaceuticals.

At the Society of Nuclear Medicine 2024 annual meeting in Toronto, we heard about the success of repeating a second round of six cycles of Pluvicto™ therapy, which challenges the dogma of limiting the radiation dose to the kidney to 23 Gray.

At the European Association of Nuclear Medicine 2024 annual meeting, we heard about successful SPECT/CT-based dosimetry for actinium-225, demonstrating even the alpha-emitting daughter products from actinium-225 concentrate in tumors and provide effective treatment and limit toxicity.

I expect 2025 will bring even bigger announcements for increased availability of alpha-emitting radiopharmaceuticals, successful phase 3 trials for FAP-targeted radiopharmaceutical therapy, and the continued search for new and better targets to exploit for successful patient care.

For the future, I believe there will be increased interest in clinical trials utilizing alpha-emitting radioisotopes such as actinium-225, lead-212, and astatine-211. The greater relative biological effectiveness of alpha radiation can allow treatment response even in patients that have progressed after beta therapies, and the shorter range of alpha emissions will decrease off-target effects and have the potential to reduce side effects.

I also believe there will be a move to use radiopharmaceuticals earlier in a patient’s disease course. Radiopharmaceuticals have traditionally been used in very late-stage disease. I expect trials will move toward assessing radiopharmaceuticals earlier in the disease course, which will change the comparators of therapies used earlier in that disease course.

One more point. I believe the success of repeating a second six cycles of Pluvicto™ therapy in a single patient will challenge the dogma of limiting the radiation dose to the kidney to 23 Gray. Trials now often allow extensions of treatment beyond the original prescribed cycles as long as patients are tolerating therapy.

I believe this will continue and the dogmatic numerical limitations will be replaced with a greater emphasis on individual subject tolerance, allowing some subjects to receive more cycles of radioligand therapy.