# Novel microscale purification methods for complete microfluidic production of high molar activity PET radiotracers

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $195,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Positron emission tomography (PET) is a real-time, in vivo 3D imaging technique with unparalleled specificity
and sensitivity for visualizing biochemical processes. These properties lend it enormous value in drug discovery
and understanding the biology of diverse diseases (e.g. in oncology, neurology, cardiology, etc.) Thousands of
different PET tracers have been synthesized to measure: (i) density of receptors or cell-surface markers, (ii)
enzyme activity, (iii) metabolism, (iv) pharmacokinetics and pharmacodynamics of drugs (by radiolabeling the
drug), and (v) response to therapy. PET will play a critical role in the emerging era of precision medicine by
providing a more complete picture of disease than is possible via biopsy and in vitro assays. Though several
PET tracers have been advanced to the clinic, the development and translation of others is hindered by limited
availability and high production cost of these short-lived compounds.
The emerging technique of micro-droplet radiochemistry can remove this bottleneck by minimizing reagent costs
and eliminating the need for large scale radiochemistry infrastructure. Furthermore, such devices can routinely
produce tracers with high molar activity (AM) – a critical quality when imaging rare biological targets (e.g.
neuroreceptors) or small animals – across a wide range of synthesis scales. In contrast, with macroscale
apparatus, high AM can typically only be achieved by using very high starting radioactivity, increasing safety
concerns, risk of radiolysis, and radioisotope cost. Micro-droplet radiochemistry is ideally suited to produce small
batches for novel tracer development, while also being capable with up-scaling by pre-concentrating the isotope.
While significant development of microfluidics for production of PET tracers has occurred in the last few years,
there has been relatively little progress in advancing microscale purification techniques for radiochemistry, aside
from miniaturization of solid-phase extraction, a technique that does not have sufficient separating power for
most tracers. Instead, microfluidic radiochemistry chips are often coupled to conventional instruments (e.g.
HPLC), undermining many of the advantages of microfluidics. In this proposal, the feasibility of using capillary
electrophoresis (CE) as a radiotracer purification method to replace HPLC is explored. CE has comparable
separating power and flexibility as HPLC, but can be readily miniaturized into low-cost microfluidic chips. In
previous work, analytical-scale CE has successfully been used to separate the tracers 3'-deoxy-3'-
[18F]fluorothymidine ([18F]FLT) and 1-(2'-deoxy-2'-[18F]fluoro-β-D-arabino-furanosyl) cytosine ([18F]FAC) from
their impurities at the analytical scale (~5-50 nL samples); however, it is not known whether this technique can
be scaled up (Aim 1) to purify the much larger (~1 µL) volume from the microdroplet synthesis chip, how best to
integrated miniature radiatio...

## Key facts

- **NIH application ID:** 9877008
- **Project number:** 5R21EB024243-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Robert Michael van Dam
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,000
- **Award type:** 5
- **Project period:** 2019-03-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9877008

## Citation

> US National Institutes of Health, RePORTER application 9877008, Novel microscale purification methods for complete microfluidic production of high molar activity PET radiotracers (5R21EB024243-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9877008. Licensed CC0.

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