Novel Radiopharmaceutical May Aid in Imaging for Patients With Neuroendocrine Tumors and Liver Metastases

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For patients with neuroendocrine tumors and liver metastases, a new radiopharmaceutical, Ga-68 DOTA-JR11, has shown a benefit in imaging for tumor detection, staging, and restaging, providing important information to guide treatment. In a head-to-head comparison of two somatostatin receptor (SSTR) imaging agents, Ga-68 DOTA-JR11 positron-emission tomography/computed tomography (PET/CT) performed better than Ga-68 dotatate PET/CT in detecting liver metastases, with a better tumor-to-background ratio, according to research published by Zhu et al in The Journal of Nuclear Medicine.

SSTRs—the key targets for imaging and peptide receptor radionuclide therapy in patients with neuroendocrine tumors—typically are imaged using Ga-68­–labeled peptides, which are agonists that bind to SSTRs to elicit a response. However, newly developed peptide antagonists, which recognize and then block SSTRs, have shown more favorable pharmacokinetics, better image contrast, higher tumor uptake, and better residence time in recent studies.

“With antagonists, we now have an alternative to agonists,” stated first study author Wenjia Zhu, MD, of the Peking Union Medical College Hospital in Bejing, China, in a statement. “However, there is still not much evidence about the performance of PET/CT imaging with SSTR antagonists. Hence, we designed this prospective study to compare Ga-68 dotatate and Ga-68 DOTA-JR11 PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors.”

Study Methods

The study included 31 patients and took place on 2 consecutive days. Each patient received an intravenous injection of Ga-68 dotatate on the first day and Ga-68 DOTA-JR11 on the second day. Whole-body time-of-flight PET/CT scans were performed 40 to 60 minutes after each injection on the same scanner. Upon completion, physiologic normal-organ uptake, lesion numbers, and lesion uptake were compared between Ga-68 dotatate and Ga-68 DOTA-JR11 PET/CT images.

Results of the Comparison

The physiologic normal-organ uptake of the spleen, renal cortex, adrenal glands, pituitary glands, stomach wall, normal liver parenchyma, small intestine, pancreas, and bone marrow was significantly lower on Ga-68 DOTA-JR11 PET/CT than on Ga-68 dotatate PET/CT. Ga-68 DOTA-JR11 was found to detect significantly more liver lesions than Ga-68 dotatate; however, Ga-68 dotatate detected more bone lesions than Ga-68 DOTA-JR11. While the radiopharmaceuticals showed similar lesion uptake for primary tumors and lymph node metastases on both patient-based and lesion-based comparisons, the target-to-background ratio of liver lesions was significantly higher on Ga-68 DOTA-JR11.

“What we’ve learned from this study is that peptides matter,” noted Dr. Zhu. “For patients with different metastatic patterns, different peptides should be used. In liver-dominant disease, Ga-68 DOTA-JR11 may be a better choice in tumor staging and restaging compared to Ga-68 dotatate. It may also change the treatment strategy, especially when partial resection or local therapy for liver metastasis is considered. In bone-dominant disease, we should probably stick to agonists, as Ga-68 DOTA-JR11 may underestimate tumor burden. We expect more extensive theranostic application of antagonists in the near future.”

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