Expert Discusses Logistical Considerations and Future Research Needs for Radiopharmaceuticals

In an interview with Pharmacy Times, Thor Halfdanarson, MD, addresses the logistical, regulatory, and manufacturing considerations associated with radiopharmaceuticals, reflfecting on what has been observed in clinical trials to date. He also discusses emerging priorities for future studies, including comparative evaluation of α and β emitters and the need for longer-term toxicity and efficacy data.

Q: Radiopharmaceuticals often present logistical, regulatory, and manufacturing challenges. Could you comment on the production, delivery, shelf life, radiolabeling stability, and clinical workflow considerations that might impact real-world use?
Thor Halfdanarson, MD: I think it remains to be seen once we wrap this up to a wider use. So far, in the context of the clinical trial, it hasn't been an issue. We've been able to treat patients at times where they were supposed to be treated, and we haven't really run into that. But as always, if you have an approval of a radioligand therapy, the big question is, can you meet the demand, which is substantial? Also, we are no longer the only tumor type competing for radioligand therapy. We saw that with prostate cancer and lutetium-177, and we're probably going to see that for a lot of other tumors. So I think as the industry goes into this prepared, my concerns for not being able to meet the demand and logistical issues are actually fairly small. We've seen with other radioligand therapies available to us that we've been able to sort all these things out.

Q: Looking ahead, what key questions must be answered in subsequent trials?
Halfdanarson: So I think in future trials, a question that is on a lot of people's mind is alpha versus beta. In patients with NETs progressing on standard first- or second-line therapy, is alpha going to have advantages over beta? That remains to be tested in larger clinical trials. Also, long-term toxicities. We've known that the renal toxicity—or the renal safety, I'll say—with lutetium is actually very good, so renal toxicity is not seen, but we do see a low risk of leukemia, two to three percent. So I think everyone is interested in seeing how the long-term results with alpha are. Some of the data we have already on alpha-treated patients are in patients who previously received beta radiation therapy, which could have been the cause of the leukemia or the MDS observed later. So going into the future, we just need longer follow-up with larger patient numbers in terms of toxicity and efficacy assessment.