18F-fluetmetamol demonstrates amyloidosis affinity

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The 11C Pittsburgh compound B (PiB) has shown that it is a useful marker for amyloidosis, a pathogenic process in Alzheimer’s disease (AD); however, a facility must have an on-site cyclotron to produce the compound. A multinational team of researchers has found that the 18F-labeled thioflavin derivative of PiB, 18F-flutemetamol, shows promise for amyloidosis affinity, according to research published in this month’s Journal of Nuclear Medicine.

“Making an accurate and reliable diagnosis of AD at the earliest disease stages is challenging and becomes increasingly important as disease-modifying therapies, such as those aimed at lowering A? amyloid, appear on the horizon,” the authors wrote.

According to researchers from Belgium, Sweden and the U.K., having a good 18F-based tracer would increase the availability of the technology by more than ten-fold. Because the 11C-PiB parent molecule has undergone extensive validation, 18F-flutemetamol has an advantage over other 18F-labeled compounds for marking amyloidosis.

Comparison of axial PET sum images of different scan lengths (5, 10, and 20 minutes) at constant scan end time (105 minutes) for one representative AD patient (AD 4) and one healthy control (HC 6). SUVR= SUV ratio. Image and caption courtesy of SNM.

“The primary aims of the current phase 1 study were to perform brain kinetic modeling of 18F-flutemetamol, select the optimal image acquisition window, and compare different methods of analysis (step 1) and to contrast 18F-flutemetamol brain retention in AD patients versus healthy controls in a proof-of-concept study (steps 1 and 2),” the authors wrote.

The scientists recruited eight patients with early-stage clinically probable AD; three participated in step 1, five participated in step 2. A control group of eight healthy volunteers was also recruited with the same distribution in steps 1 and 2.

The 18F-flutemetamol was injected intravenously as a slow bolus in an antecubital vein and dynamic brain scanning was performed using a 16-slice Biograph PET/CT scanner (Siemens Healthcare) in 3D list mode.

In step 1, PET data acquisition was started at the time of tracer injection and lasted for 90 minutes; a second period of data acquisition ran from 150 to 180 minutes, and a third ran from 220 to 250 minutes. In step 2, the acquisition procedure was simplified on the basis of time–activity curves obtained in step 1; data acquisition was limited to 80–170 minutes after injection, the scientists reported. The PET data was reconstructed using Fourier rebinning and 2D ordered subsets expectation maximization.

In addition, 30 days prior to the PET/CT study, each participant had an MRI (Intera 1.5T, Philips Healthcare) scan performed. The MRI scan was co-registered to the PET summed image using a mutual information–based method.

The scientists reported that from 80 minutes after injection onward, the ratio of neocortical to cerebellar uptake was maximal and only marginally affected by scan start time or duration. They also noted that the spatial distribution of the 18F-flutemetamol uptake in their AD patients closely resembled that seen with the 11C-PiB compound.

“AD patients showed significantly increased standardized uptake value ratios in neocortical association zones and striatum, compared with healthy controls, whereas uptake in white matter, cerebellum, and pons did not differ between groups,” the authors wrote. “The retention of 18F-flutemetamol was similar in AD patients and healthy controls in brain regions known to be relatively unaffected by amyloid deposition, such as pons, cerebellum and subcortical white matter.”

Based on these initial results, the researchers strongly believe that further testing with 18F-flutemetamol is warranted.

“These phase 1 results justify further pursuit of 18F-flutemetamol as a biomarker for AD-related amyloidosis with wider availability for clinical and research purposes than its ‘parent molecule,’ 11C-PiB,” they concluded.