Breaking the Boundaries Between Radiology and Oncology: Thomas A. Hope, MD

Thomas A. Hope, MD, Associate Professor, Director of Molecular Therapy in the Department of Radiology and Biomedical Imaging, University of California, San Francisco (UCSF), spoke with GU Oncology about his unusual career path. He explained how it has led to his work in a unique area of medicine with one metaphorical foot in nuclear medicine and the other in medical oncology—researching novel imaging agents and therapies in neuroendocrine tumors and prostate cancer.

Throughout most of his life, Dr Hope has lived and worked in San Francisco, California. He has been working at the UCSF Department of Radiology and Biomedical Imaging since 2013. “Although I trained as a radiologist, the vast majority of what I do on a day-to-day basis is nuclear medicine,” he stresses. He combines his research work at UCSF with his role as Associate Chair for Business Strategy for Radiology and his responsibilities as Chief of Nuclear Medicine at the San Francisco VA Medical Center. “I’m very splintered between research, clinical, and administration and teaching at the VA,” he admits.

Dr Hope is probably best known currently for his role in leading the development of the radiopharmaceutical gallium-68 prostate-specific membrane antigen (PSMA)-11 (Ga 68 PSMA-11) for positron emission tomography (PET) imaging of PSMA-positive lesions in men with prostate cancer. His team’s work, in cooperation with UCLA researchers, led to regulatory approval of ⁶⁸GA-PSMA-11 by the Food and Drug Administration (FDA) on December 1, 2020.¹

Dr Hope’s career path to his current position has been anything but straightforward. “It’s been like hopping on stones between research projects to the space where I am now,” he says. “I had no idea 10 years ago that I would be doing what I’m doing today.”

Although he was interested in science early on, his initial ambitions were not focused on a medical career. After attending Duke University in Durham, North Carolina, he graduated with a combined BA/BS degree, majoring in biology and economics, in 2001. “Duke was a wonderful school, a great experience, but I have no idea why I went there,” he admits. “What I really wanted to be was a businessman.”

From 2001 to 2003 Dr Hope was employed by a Boston strategy consulting firm that worked with start-up biotech companies. “It was very interesting, but I realized that I did not want to do business,” he recalls. “I took the Medical College Admission Test (MCAT) and then it took about a year for me to figure out that I wanted to go to med school,” he says. In 2007, he received his medical degree from Stanford University, after which he entered a one-year internship at Kaiser Permanente San Francisco Medical Center. He completed a residency in diagnostic radiology at UCSF, followed by a clinical fellowship in body MRI and nuclear medicine fellowship at Stanford Medical Center.

Venturing Into Radiology

Dr Hope maintains that initially, he had little idea about which medical specialty to choose, but he attributes his final choice to his older brother, Michael D. Hope, MD, currently Professor in Residence and Vice-Chair in the Department of Radiology and Biomedical Imaging at UCSF, “and also my boss as Chief of Radiology at the San Francisco VA Health Care System,” Dr Hope (the younger) adds. “I looked at different specialties, but my brother was going into radiology, so I thought, ‘That sounds cool, so I did research in radiology.’”

Dr Hope’s first research interest was in cardiac magnetic resonance imaging (MRI). At Stanford, Dr Hope worked with Robert J. Herfkens, MD, now Professor of Radiology (Cardiovascular Imaging), Emeritus. “He was the mentor who changed my career most,” Dr Hope says “He helped set up a fellowship at Stanford that was shared between nuclear medicine and body MRI and really, without his direction and pushing, I never would have gone down that path,” he acknowledges.

Dr Hope came to his UCSF faculty position very excited about molecular imaging and PET/MRI. “My first real research project was evaluating a new radiotracer called Ga 68 DOTATOC, a PET radiopharmaceutical used in neuroendocrine tumors,” he recalls. “We were an early adopter of somatostatin receptor-directed PET imaging. We got a Ga-68 generator and I learned how to write INDs and protocols dealing with all this clinical research that I had no experience in through that project.

Through that project, Dr Hope started to consider imaging prostate cancer patients with Ga 68 DOTATOC PET and whether another imaging modality might be needed. “Then in 2014-2015 I went down the rabbit hole of PSMA,” he says. The first patient was imaged with Ga 68 PSMA-11 PET in April 2015. “We were doing neuroendocrine prostate cancer imaging and once we started that, I realized that there was a lot more opportunity with PSMA PET, and in December 2015, we started doing gallium 68 PSMA-11 PET. Then the dam broke. We had a trial with a 225 patient protocol that we thought would probably take 3 years and we enrolled in 7 months.² After I saw how successful that was, we started to consider how a generic agent like this could get FDA approval.” Starting in 2016, they worked to create the data set needed to get approval of Ga 68 PSMA-11, which happened 4 years later.

Dr Hope pays tribute to Johannes Czernin, MD, Chief of the Ahmanson Translational Imaging Division at UCLA, for his work as co-leader in the joint development of Ga 68 PSMA-11 by the two institutions. “That collaboration with UCLA was the best part of my career,” Dr Hope says. “It was a productive, positive, team with many unique achievements.” One was the first approval of 2 NDAs for the same drug simultaneously. “Neither UCSF nor UCLA claimed exclusivity,” Dr Hope explains. “We wanted other people to either get NDAs or use the data to get their own drug approved. That was validated when Telix got approval for their Ga 68 PSMA-11 preparation kit.” ³

“Hopefully, in a year and a half, we’ll succeed in following up on PSMA with other types of drugs that are generic,” Dr Hope predicts.

Ongoing Endeavors in Radiology and Oncology

His current research includes cooperation with UCSF basic scientists doing CRISPR screening to try to identify compounds that will modulate PSMA expression.  He will soon begin a clinical trial of pretreatment in patients prior to PSMA radioligand therapy to increase their expression of PSMA. “It’s like bench to bedside, taking this radioligand therapy, modulating the target, and actually seeing if we improve the therapy. It would be very cool if that works,” he comments.

Several combination therapy trials are underway at UCSF, including a trial of pembrolizumab plus lutetium-177 (¹⁷⁷Lu)-PSMA-617 in treating patients with metastatic castration-resistant prostate cancer (NCT03805594), led by Rahul Aggarwal, MD. Dr Hope is also collaborating on a trial of pembrolizumab and lutetium Lu-177 dotatate in neuroendocrine tumors (NCT03457948), led by Nicholas Fidelman, MD.

He is also working on commercial radioligand therapy trials. He is national PI on the LuMIERE trial (NCT04939610) with ¹⁷⁷Lu-FAP-2286, a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). “I’m very interested in how we can use dosimetry to modulate the dose of radioligand therapy to improve patient outcomes,” he reflects.

Dr Hope also spends one day a week at his clinic, seeing patients who are on radioligand therapies for neuroendocrine tumors or prostate cancer. “Not many nuclear medicine radiologists see patients,” he notes, “but I believe that it’s important to do that. I would really love to see the field have more ownership over the patient.”

Dr Hope has no doubts about the future of nuclear medicine as a career choice. “I think nuclear medicine is dynamic and active, drugs are being approved, there’s investment – it’s a wonderful field,” he declares. But he cautions, “Every field has a time when there’s a lot of innovation and excitement.” He points to anesthesia in the 60s and cardiology in the 90s, where “everything was new and happening and now they have become more stable and innovation has slowed down,” he says. “Nuclear medicine right now is in that moment where everything’s happening, it’s exciting, new drugs are coming through, trials are ongoing; we’re reinventing how to treat patients now.”

“We’ve got an opportunity to really define the field in the way medicine is practiced, which is pretty cool,” Dr Hope says. “There aren’t many places you get that opportunity.” He adds, “The way we’re doing radioligand therapy right now will not be at all how we do it in 10 years’ time. There’s going of be a group of people in nuclear medicine right now who are going to define that and who are going to set the standard of how we do this moving forward. It’s very exciting to be in that space,” he advises.

Linda Brookes, MSc is a freelance medical writer/editor based in New York and London.

References

1. FDA approves first PSMA-targeted PET imaging drug for men with prostate cancer for immediate release. Food and Drug Administration; December 01, 2020. Accessed March 12, 2022. https://www.fda.gov/news-events/press-announcements/fda-approves-first-psma-targeted-pet-imaging-drug-men-prostate-cancer
2. Lawhn-Heath C, Flavell RR, Behr SC, Yohannan T et al. Single-center prospective evaluation of ⁶⁸Ga-PSMA-11 PET in biochemical recurrence of prostate cancer. AJR Am J Roentgenol. 2019;213(2):266-274. DOI: 2214/ajr.18.20699
3. FDA approves Telix’s prostate cancer imaging product, Illuccix^®. Telix; December 20, 2021. Accessed March 12, 2022. https://bit.ly/3J8Wgan