Spatial Distribution of Brain PET Tracers by MALDI Imaging

Area of Science:

• Pharmacology
• Analytical Chemistry
• Biomedical Imaging

Background:

• Positron Emission Tomography (PET) tracer development traditionally uses autoradiography for tissue distribution analysis.
• Autoradiography requires radioactive compounds, posing safety and disposal challenges.
• Mass Spectrometry Imaging (MSI) presents a non-radioactive alternative with comparable spatial resolution.

Purpose of the Study:

• To optimize a Mass Spectrometry Imaging (MSI) sample preparation protocol for evaluating PET tracer candidates ex vivo.
• To assess the impact of different matrices and washing steps on PET tracer detection using MSI.
• To establish a quantitative MSI method for PET tracer distribution analysis.

Main Methods:

• Optimization of MSI sample preparation protocols for PET tracers UCB-J and UCB2400.
• Inclusion of washing steps in the sample preparation to enhance tracer signal.
• Preparation of tissue homogenates for constructing calibration curves for quantification.
• Comparison of different matrices for MSI analysis.

Main Results:

• The incorporation of a washing step significantly enhanced the detection signal for both UCB-J and UCB2400 PET tracers.
• The optimized MSI protocol minimized ion suppression effects, improving quantification accuracy.
• MSI demonstrated potential for cost-effective and efficient evaluation of PET tracer distribution.

Conclusions:

• MSI is a viable, non-radioactive alternative to autoradiography for assessing PET tracer distribution.
• An optimized MSI sample preparation protocol, including washing steps, enhances tracer signal and quantification.
• This optimized MSI approach provides a valuable tool for preclinical PET tracer evaluation.