QUESTION: Is sequential intraarterial–intravenous 177 Lu-DOTATATE peptide receptor radionuclide therapy PRRT with personalized dosing feasible for increasing radiation to liver metastases in progressive, nonresectable gastroenteropancreatic neuroendocrine tumors (NETs)?
PERTINENT FINDINGS: Intraarterial administration is feasible and delivers over three times more radiation to liver metastases than intravenous administration. Partial response rates were 67 percent after three months and 87 percent after six months, with no severe route-related toxicity.
IMPLICATIONS FOR PATIENT CARE: The hybrid intraarterial–intravenous PRRT approach may enhance treatment of liver-dominant metastatic gastroenteropancreatic NETs by intensifying radiation to the liver and maintaining systemic coverage without added major toxicity.
Reston, VA (November 12, 2026) —Combining intraarterial and intravenous administration of peptide receptor radionuclide therapy (PRRT) can selectively intensify treatment for liver-dominant metastatic neuroendocrine tumors (NETs) while still effectively delivering treatment throughout the whole body. This hybrid approach safely delivered over three times more radiation directly to liver metastases, resulting in encouraging tumor responses among patients. This research was published online in The Journal of Nuclear Medicine .
Once considered rare, gastroenteropancreatic NETs now show increasing incidence and prevalence. Diagnosis often occurs late, usually with liver metastases, making surgery—the only curative option—unfeasible. Current liver-directed (or hepatic) therapies, such as systemic agents, chemotherapy, and PRRT, offer symptom and tumor control, with a median progression-free survival of approximately 1.5 years.
“Research has shown that standard intravenous PRRT may not deliver enough radiation to these lesions,” said Lisa Bodei, MD, PhD, attending physician, member, and director of RadioTheranostics Section, Molecular Imaging and Theranostics Service in the Department of Radiology at Memorial Sloan Kettering Cancer Center and professor of radiology at Weill Cornell Medical College of Cornell University, in New York. “Our study explored a personalized hybrid approach—delivering the first treatments directly through hepatic arteries, followed by intravenous therapy—and sought to determine if this treatment method was feasible, safe, and effective.”
The prospective pilot study included 10 patients with progressive, liver-dominant metastatic gastroenteropancreatic NETs. The patients received four cycles of 177 Lu-DOTATATE administered every two months: two initial intraarterial cycles followed by two intravenous cycles. Safety monitoring, radiation protection, and dosimetry comparisons between intraarterial and intravenous routes were performed and preliminary efficacy was evaluated.
The intraarterial administration procedure was feasible in 100 percent of patients. Radiation exposure to staff and patients remained within regulatory limits, with no contamination events. Dosimetry analysis indicated that intraarterial administration delivered a greater than three-fold higher radiation dose to liver metastases compared with the intravenous route.
Furthermore, 68 Ga-DOTATATE PET imaging revealed an 86 percent increase in median liver lesion uptake with intraarterial administration. Efficacy analysis showed partial response rates in 67 percent of patients at the first follow-up three months after treatment completion, improving to 87 percent at the second follow-up six months after treatment completion.
“The novelty of this research is not simply that liver-directed intraarterial PRRT increases hepatic uptake; rather, it evaluates a clinically integrated, personalized hybrid strategy that links delivery, dosimetry, safety, and response within the same prospective study,” said Bodei. “For patients, this could translate into better tumor control and a more effective, individualized treatment option.”
The authors of “ Optimizing the Therapeutic Index: Sequential Intraarterial–Intravenous PRRT with Personalized Volumetric-Adjusted Dosing ” include Lisa Bodei and Heiko Schöder, Molecular Imaging and Therapy, Memorial Sloan Kettering Cancer Center, New York, New York, and Department of Radiology, Weill Cornell Medical College of Cornell University, New York, New York; Etay Ziv, Department of Radiology, Weill Cornell Medical College of Cornell University, New York, New York, and Interventional Radiology Services, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; Audrey Mauguen, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York; Pat Zanzonico, Bae Chu, and Joseph A. O’Donoghue, Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York; Diane Reidy and Nitya Raj, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Adrian Gonzalez-Aguirre, Interventional Radiology Services, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; and Jonathan Kuten, Molecular Imaging and Therapy, Memorial Sloan Kettering Cancer Center, New York, New York.
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Journal of Nuclear Medicine
Optimizing the Therapeutic Index: Sequential Intraarterial–Intravenous PRRT with Personalized Volumetric-Adjusted Dosing