Although it had been in trial use for some years in Europe and elsewhere, the formal approval of 68Ga-DOTATATE has led to an increase in the development of other radionuclides, some in conjunction with therapeutic options (i.e. PRRT) making a ‘theranostic’ approach to diagnosing, treating and surveillance Neuroendocrine Cancer patients with somatostatin receptor positive tumours. I also wrote last year about another option called 64Cu, something already available in Europe, in particular Denmark.
In another development which has been running for some time, a Ga68 variant called 68Ga-DOTA-JR11 has been in trial and specialists have carried out a study comparing it with 68Ga-DOTATATE (often referred as NETSPOT in USA).
For neuroendocrine cancer patients with liver metastases, a new radiopharmaceutical, 68Ga-DOTA-JR11, has shown excellent imaging performance in tumor detection, staging, and restaging, providing important information to guide treatment.
In a head-to-head comparison of two somatostatin receptor (SSTR) imaging agents, 68Ga-DOTA-JR11 PET/CT performed better than 68Ga-DOTATATE PET/CT in detecting liver metastases, with a better tumor-to-background ratio, according to research published in the June issue of The Journal of Nuclear Medicine.
SSTRs–the key target for imaging and peptide receptor radionuclide therapy in patients with neuroendocrine tumors–typically are imaged using 68Ga-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 favourable pharmacokinetics, better image contrast, higher tumor uptake, and better residence time in recent studies.
“With antagonists, we now have an alternative to agonists,” stated Wenjia Zhu, MD, nuclear medicine physician, at Peking Union Medical College Hospital in Bejing, China.
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 68Ga-DOTATATE and 68Ga-DOTA-JR11 PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors.”
Wenjia Zhu, MD, Nuclear Medicine Physician, Peking Union Medical College Hospital, Bejing, China
The study included 31 patients and took place on two consecutive days. Each patient received an intravenous injection of 68Ga-DOTATATE on the first day and 68Ga-DOTA-JR11 on the second day. Whole-body time-of-flight PET/CT scans were performed 40-60 minutes after each injection on the same scanner.
Upon completion, physiologic normal-organ uptake, lesion numbers, and lesion uptake were compared between 68Ga-DOTATATE and 68Ga-DOTA-JR11 PET/CT images. 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 68Ga-DOTA-JR11 PET/CT than on 68Ga-DOTATATE PET/CT. 68Ga-DOTA-JR11 was found to detect significantly more liver lesions than 68Ga-DOTATATE; however, 68Ga-DOTATATE detected more bone lesions than 68Ga-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 68Ga-DOTA-JR11.
“What we’ve learned from this study is that peptides matter,” noted Zhu. “For patients with different metastatic patterns, different peptides (DOTA-JR11 versus DOTATATE) should be used. In liver-dominant disease, 68Ga-DOTA-JR11 may be a better choice in tumor staging and restaging compared to 68Ga-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 68Ga-DOTA-JR11 may underestimate tumor burden. We expect the more extensive theranostic application of antagonists in the near future.”
Zhu, W., et al. (2020) Head-to-Head Comparison of 68Ga-DOTA-JR11 and 68Ga-DOTATATE PET/CT in Patients with Metastatic, Well-Differentiated Neuroendocrine Tumors: A Prospective Study. Journal of Nuclear Medicine. doi.org/10.2967/jnumed.119.235093.
Also worth pointing out that JR11 is also associated with the radionuclide used in PRRT clinical trial of Lutetium-177 OPS-201 (Satoreotide) – I wrote about that here. JR11 as a PET scan radionuclide is sometimes described as OPS202.
Other interest points:
1. In a phase 1 study to assess Safety, Biodistribution, and Radiation Dosimetry of 68 Ga-OPS202 in Patients With Gastroenteropancreatic Neuroendocrine Tumors concluded “68Ga-OPS202 showed favorable biodistribution and imaging properties, with optimal tumor contrast between 1 and 2 h after injection. Dosimetry analysis revealed that the dose delivered by 68Ga-OPS202 to organs is similar to that delivered by other 68Ga-labeled sst analogs. Further evaluation of 68Ga-OPS202 for PET/CT imaging of NETs is therefore warranted.” Read more here.
2. Agonists vs Antagonists. The approved Ga68 DOTATATE is technically known as an ‘agonist’ whereas Ga68-DOTA-JR11 is an ‘antagonist’. This is a highly complex area but the difference is in the way the mix binds to the somatostatin receptor (SSTR) Agonists typically bind to a SSTR to elicit a response, however, antagonists recognise and then block SSTRs.
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