NRC Considers Additional Training, Experience Requirements for Radiopharmaceuticals

Earlier this month, the US Nuclear Regulatory Commission (NRC) published a notice in the Federal Register announcing a 30-day public comment period and two public meetings on the NRC staff’s draft approaches regarding training and experience requirements for administration of radiopharmaceuticals requiring a written directive. 

This is one of several information-gathering activities that will help the agency decide whether to open this issue to rule making. The society’s expert work group will address the open notice and questions included in the notice. Although SNMMI will be submitting comments, all members are encouraged to submit their own comments. The comment period will end on June 3, 2019.

The NRC is also accepting oral comments during public meetings, which will be accessible for remote participation by moderated bridge line and webinar. NRC’s public meeting website will be updated with meeting details.

SNMMI previously submitted comments to the NRC on training and experience requirements for authorized users for medical uses under Subpart E, “Unsealed Byproduct Material — Written Directive Required.” SNMMI comments highlight the importance of patient and public safety, while ensuring access to quality care. These are available here.

New PET Imaging Biomarker Could Better Predict Progression of Alzheimer’s Disease

Researchers have discovered a way to better predict progression of Alzheimer’s disease. By imaging microglial activation levels with PET, the researchers were able to better predict progression of the disease than with beta-amyloid PET imaging, according to a study recently published in The Journal of Nuclear Medicine.

According to the Alzheimer’s Association, an estimated 5.3 million Americans are currently living with Alzheimer’s disease. By 2025, that number is expected to increase to more than 7 million. The hallmark brain changes for those with Alzheimer’s disease include the accumulation of beta-amyloid plaques. When microglial cells from the central nervous system recognize the presence of beta-amyloid plaques, they produce an inflammatory reaction in the brain.

“The 18-kD translocator protein (TSPO) is highly expressed in activated microglia, which makes it a valuable biomarker to assess inflammation in the brain,” says Matthias Brendel, MD, MHBA, at Ludwig-Maximilians-University of Munich in Germany. “In our study, we utilized TSPO-PET imaging to determine whether microglial activation had any influence on cognitive outcomes in an amyloid mouse model.”

For the study, researchers compiled a series of PET images for 10 transgenic mice with beta-amyloid proteins and seven wild-type mice. TSPO-PET imaging of activated microglia was conducted at eight, 9.5, 11.5, and 13 months, and beta-amyloid PET imaging was performed at eight and 13 months. Upon completion of the imaging, researchers then subjected the mice to a water maze in which the mice were to distinguish between a floating platform that would hold their weight and one that would sink. The tasks were performed several times a day during a 1.5-week period. Memory performance in the water maze was assessed by measuring the average travel time from the start point to a platform each day of training and by calculating the traveled distance at the last day of training. After completing the water maze task, immunohistochemistry analyses were performed for microglia, amyloid, and synaptic density.

Transgenic mice with the highest TSPO-PET signal in the forebrain or other areas associated with spatial learning tended to have better cognitive performance in the water maze, while beta-amyloid signals in the same areas of the brain showed no correlation to cognitive outcomes in the maze. Researchers found that an earlier microglial response to amyloid pathology in transgenic mice also protected synaptic density at follow-up. Specifically, transgenic mice with higher TSPO expression at eight months had much better cognitive outcomes in the water maze and higher synaptic density as confirmed by immunohistochemistry analyses.

“This study provides the first evidence that the level of microglial activation could be a far better predictor of current and future cognitive performance than beta-amyloid levels,” Brendel says. “Keeping the limitations of mouse models in mind, it could be crucial to modify an individual’s microglial activation state to ameliorate future cognitive decline. We believe that a balanced microglia activation is crucial for prevention of cognitive impairment.”

PRRT Shows Long-Term Effectiveness for Malignant Neuroendocrine Tumors

A 12-year retrospective clinical study of patients who received peptide receptor radionuclide therapy (PRRT) for malignant neuroendocrine tumors demonstrates the long-term effectiveness of this treatment, which also allows patients to maintain a high quality of life. The study is featured in the April issue of The Journal of Nuclear Medicine.

While PRRT has been used for more than 20 years to treat patients with inoperable or metastatic somatostatin receptor-positive tumors, knowledge of long-term outcomes has been limited. A number of clinical studies have demonstrated PRRT’s efficacy, and the overall response rate, including complete response, partial response, minor response, and stable disease, is about 70% to 80% for the two most commonly used radiopharmaceuticals: yttrium-90 (Y-90)-DOTATOC—best suited for treating larger tumors—and lutetium-177 (Lu-177)-DOTATATE—preferred for smaller tumors. For patients who respond to PRRT, the prognosis is generally favorable, with a median time to disease progression of three to four years.

The study included 44 patients (27 men and 17 women) with advanced tumors and enhanced somatostatin receptor expression. Mean age at initial diagnosis was 60 years with an age range of 40 to 84. Median follow-up was 80 months. For Lu-177-PRRT, the mean number of cycles administered was 5.3 ± 2.5; for Y-90-PRRT, the mean number of cycles administered was 5.5 ± 2.6.

Median overall survival was 79 months, but 32% of the patients (14 of 44—six men and eight women) were still alive more than 12 years after starting PRRT. Progressive disease occurring early after therapy began resulted in a poor prognosis, while women and patients with no more than two tumor sites seemed to benefit the most from PRRT.

“This study clearly demonstrates the long-term efficacy of PRRT over more than a decade in patients with metastatic tumor disease of neuroendocrine origin,” according to Michael Gabriel, MD, and Irene J. Virgolini, MD, of the department of nuclear medicine at the Medical University of Innsbruck in Austria. They add that, according to the research, “PRRT can be repeatedly used with limited side effects. From this perspective, a relatively stable tumor situation can be achieved over many years in a large number of patients. None of the patients who were still alive at the end of the observation period were dialysis dependent, and most of the patients showed a still very high [key performance indicator], which underlines the positive effect of PRRT in terms of the quality of life.”

Gabriel and Virgolini also point out the value of molecular imaging in therapeutic decision making and, looking ahead, recommend “new prospective studies combining the nuclear medicine therapy approach with other therapeutic modalities to further increase efficiency.”

Source: SNMMI