PET/CT Biodistribution in NHP Models For CNS Drug Delivery

In Vivo Imaging for CNS Drug Delivery Optimization and Biodistribution Analysis

In central nervous system (CNS) drug development, two problems keep returning: getting a molecule across the blood-brain barrier (BBB), and knowing how much of it actually reaches the brain region you care about. Nose-to-brain (N2B) delivery offers a non-invasive route around the BBB, carrying drug to the brain along the olfactory and trigeminal pathways. Measuring what arrives is the harder half. Conventional ex vivo tissue homogenization returns one timepoint per animal, so a continuous pharmacokinetic (PK/PD) or biodistribution profile never emerges from the data.

At Prisys Biotech we combine radiotracer labeling with clinical-grade PET/CT imaging, which turns drug distribution in non-human primate (NHP) models into a signal that can be quantified while the animal is still alive. Repeated scans in the same subject replace a series of sacrificed cohorts, and the translational framework that comes out of it holds up for evaluating novel CNS delivery systems.

Imaging-Based Optimization of Intranasal Delivery Parameters

Effective N2B delivery depends on where the formulation lands in the upper nasal cavity. The olfactory region carries most of the weight here, since it sits closest to the direct transport pathways into the brain. Deposition is sensitive to administration parameters, in particular how the animal is positioned and how the delivery device is shaped.

Prisys has built an imaging-guided optimization workflow around CT and MRI contrast agents in cynomolgus monkeys. By varying delivery conditions one at a time, we observed that a supine position with head tilt, combined with a controlled nozzle angle (e.g., ~45°), significantly improves deposition efficiency. Under those optimized conditions, administration of a defined volume (e.g., 40 µL) of contrast agent produced approximately 50% localization within the olfactory region.

That sort of imaging-based validation gives the pharmacological studies that follow a standardized and reproducible starting point, instead of an assumed one.

INTEGRATED N VVO IMAGING PLATFORM FOR PRECLINICAL CNS DRUG DEVELOPMENT

Radiolabeling and PET/CT-Based Quantitative Biodistribution

To characterize where a candidate goes after N2B delivery, the compound itself can be radiolabeled. Positron-emitting isotopes (e.g., ^18F-labeled tracers) allow the drug molecule to be followed in vivo rather than inferred from plasma concentrations.

Following non-invasive administration, Prisys performs dynamic PET/CT imaging in NHP models, which captures drug distribution in target brain regions and in peripheral clearance organs within the same scan session. The Biodistribution Imaging Service reports cover:

Absolute quantification of tissue exposure
Time-resolved biodistribution profiles
Evaluation of BBB bypass efficiency

Set against traditional endpoint sampling, PET/CT-based imaging allows longitudinal assessment within the same subject. Data consistency improves as a result, and inter-animal variability falls, because each animal serves as its own baseline.

Advanced 3D Imaging Reconstruction and Quantitative Analysis

Reading imaging data well depends on post-processing. PET carries the molecular signal but little anatomy, so the functional dataset has to be mapped onto a reference with recognizable structure. At Prisys, PET functional data are co-registered with high-resolution anatomical images from CT or MRI, which is what makes precise spatial localization possible.

On the Clinical Imaging platform, brain regions are segmented semi-automatically or automatically, and regional tracer uptake values are extracted from those segmentations. The output is a high-resolution, three-dimensional quantitative picture of drug distribution across specific brain nuclei and functional regions.

Analyses at that resolution support detailed evaluation of target engagement, and they show how heterogeneous regional exposure really is.

Functional Validation Using fMRI

Physical distribution is only half the question. The biological activity of a delivered compound can be read with functional imaging. Prisys integrates functional MRI (fMRI) techniques, including arterial spin labeling (ASL), to evaluate pharmacodynamic effects in vivo.

In studies of intranasal insulin delivery, for example, ASL-fMRI was used to monitor regional cerebral blood flow (rCBF) in cynomolgus monkeys. Quantitative analysis demonstrated statistically significant reductions in rCBF in specific brain regions, including the amygdala and hippocampus. Those findings are consistent with observations reported in human studies, which is part of what supports the translational relevance of the NHP model.

Structural and functional imaging used together let a single study report both where the drug went and what it did when it got there.

Integrated Imaging Platform for Translational CNS Research

By combining optimized N2B delivery, radiotracer labeling, PET/CT imaging, and multimodal data analysis, Prisys Biotech provides an in vivo imaging platform for CNS drug development that covers the whole chain from dosing to readout.

This platform supports:

Quantitative biodistribution analysis
Evaluation of novel delivery systems
Integration of PK/PD and functional endpoints
Improved prediction of clinical outcomes

Through these capabilities, Prisys enables more informed decision-making in early-stage drug development and facilitates the translation of CNS therapeutics from preclinical research to clinical application.

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