The use of stable magnetic particles enables the longitudinal and quantitative biodistribution of cells, enabling the determination of cell pharmacokinetics, absorption rate, elimination rate, saturation dose and dose optimization.

Cells can be labeled with commercial particles, and particles in development.
The pEPR method allows an easy translation to the clinic: when cells are labeled with Rienso^®/Feraheme^®, this is an off-label use of the FDA approved pharmaceutical drug, and when pEPR is combined with 1.5T or 3T MRI.

Example: quantitative biodistribution of pre-labeled cells in mice, accurate localization with in-vivo MRI followed by quantification with ex-vivo pEPR (peer reviewed article in preparation).

Example: cell elimination rate in the lungs for the pre-labeled cells in mice with ex-vivo pEPR (peer reviewed article in preparation).
State of the art on cell labeling with iron oxide particles and cell tracking with MRI …

Learn more about the results on stable cell labeling, pre-labeling tests for pEPR…
Learn more about the pilot study on longitudinal and quantitative bio-distribution of pre-labeled stem cells with pEPR …
Learn more about sampling and measurement protocol for pEPR …

Magnetic nanoparticles can be quantified in tissue and blood samples with the pEPR method to study the distribution and migration of the particles in the animal body, and to determine the absorption and elimination rate of the particles in the different tissues, and to determine the saturation dose and optimal dose repetition time.

Example: the blood-clearance time was determined of particles administered to rats. Blood analysis was performed with PPS at different time points after particle injection.

Example: the correlation between particle dose and particle accumulation in the lungs was measured by quantification with pEPR of the particles in lung biopsies of pigs.

Learn more about particle pharmacokinetics and biodistribution with pEPR …
Learn more about sample and measurement protocol  for pEPR…
And in a benchmark study pEPR is compared against ICP-MS, learn more about this benchmark study …

Although the PPS is designed for particle quantification, also pEPR spectra can be obtained with the instrument. The resonant signal of the particles is measured as a function of the applied magnetic field resulting in the broad iron EPR spectrum combined with the Langevin function. The pEPR spectra give valuable information on the more fundamental magnetic characteristics of the particles. The spectra can reveal for example the influence of the coating on the magnetic particle core. Also the magnetization can be investigated as function of particle dimensions, crystal structure, synthesis process and more. These studies give valuable information for the development of new theranostic magnetic nanoparticles as a target specific contrast for MRI, as drug carrier or particles for hyperthermia.

Today, the implementation of the pEPR spectra as a standard measurement feature integrated in the firmware of the PPS tool can be requested by the user.

The ex-vivo PPS quantifies magnetic nanoparticles:
– SPIO, USPIO, MNP, and magnetic contrast agents;
– target specific iron oxide particles, magnetic drug carriers, particles for hyperthermia and thermo-ablation;
– multi-modal contrast agents with magnetic nanoparticle cores;
– pre-labeled cells, therapeutic cells, stem cells labeled with magnetic nanoparticles.

The ex-vivo PPS enables PK-studies of cell therapies and magnetic particle therapies and diagnostics:
– Pharmacokinetics, absorption and elimination rate, for example blood clearance time, cell and particle migration, saturation and clearance of target tissue, saturation dose, optimal dose repetition time, efficacy of particle coating for targeting.

Complementing pre-clinical MRI with supporting quantitative data for molecular imaging and cell imaging.

Translation to the clinic:
– pEPR combined with 1.5T or 3T MRI,
– cells labeled with Rienso^®/Feraheme^®, this is an off-label use of the FDA approved pharmaceutical drug.

The ex-vivo PPS offers instant quantitative results in minutes time, no post-processing of spectra is required.

The ex-vivo PPS offers direct quantification:
– No disturbance from endogenous iron molecules naturally present in for example blood or liver;
– All organ tissues and raw blood samples can be analysed, also lung samples complementing MRI images.

Avoid sampling errors and win time since no sample preparation or manipulation of blood or tissue is required.

Key Features include:

• Instant quantitative results
• Direct and selective for magnetic nanoparticles
• No sample preparation required, eliminating manipulation errors
• Non-destructive, tissues are conserved for further biochemical analysis
• Non-invasive for labeled cells, cells remain viable and keep their functionality
• MRI compatible Data.
• Easy to Use, minimal Hands-on
• Automated 720 PCR tube measurements per 24 hours

Learn more about PPS4S-AS …

Pepric’s detection principle is based on pEPR, particle Electron Paramagnetic Resonance.

pEPR yields sensitive and accurate results. The actual detection limit achieved to date is 10ng(Fe)/150µL for Rienso^® as well as for for Resovist^® in aqueous suspension, this comes down to 180 pmol(Fe)/150µL or 67µg(Fe)/L or 1.2µM(Fe).

pEPR is a direct measurement of particle quantity. When a RF-field is applied, the pEPR signal amplitude is proportional to the particles in resonance.
pEPR is selective for magnetic nanoparticles, and not for endogenous iron present in biological tissues and fluids; more on selectivity …
pEPR is compatible with many magnetic nanoparticles (size, shape, coatings, …); more on compatibility …

Sample and measurement protocol for pEPR …

Use and applications of pEPR for cell quantification and magnetic particle quantification below!

• Biodistribution and Pharmacokinetic studies of iron oxide nanoparticles using particle Electron Paramagnetic Resonance, MRI and ICP-MS, OL Gobbo, F Wetterling, P Vaes, S Teughels, F Markos, D Edge, CM Shortt, K Crosbie-Staunton, MW Radomski, Y Volkov and A Prina-Mello, Nanomedicine 2015, Vol. 10, No. 11, Pages 1751-1760. doi: 10.2217/nnm.15.22;

• Pharmacokinetics and bio-distribution of novel super paramagnetic iron oxide nanoparticles (SPIONs) in the anaesthetized pig, Edge D, Shortt M, Gobbo OL, Teughels S, Prina-Mello A, Volkov Y, MacEneaney P, Radomski MW, Markos F, Clinical and Experimental Pharmacology and Physiology CEPP 2016, 43, 319–326, doi: 10.1111/1440-1681.12533;

• Quantitative molecular MRI of atherosclerosis, chapters 2 and 4 in PhD thesis of Rik P.M. Moonen, promotor professor K. Nicolay, TU Eindhoven, February 2015;

• Quantification of superparamagnetic nanoparticle concentration using particle Electron Paramagnetic Resonance: an in vitro and in vivo validation study, OL Gobbo, F Wetterling, P Vaes, S Teughels, F Markos, D. Edge, CM Shortt, K Crosbie-Staunton, MW Radomski, Y Volkov, and A Prina-Mello, Scientific and Clinical applications of Magnetic Carriers 2014, presentation at Dresden; June 10-14;

• Non-invasive quantification of cells using magnetic particles and Electron Paramagnetic Resonance, Jesse Trekker, Peter Vaes, Sonu Sharma, Ashwini Atre, Stephanie Teughels and Uwe Himmelreich, WMIC 2012, Dublin, P 584;

Pepric nv
Kapeldreef 60
3001 Leuven
Belgium

You’ll find Pepric’s office at the building of I&I Leuven. You can reach us:

By car, coming from Brussels:
1. Take the E40 direction to Liège (Luik) – Cologne (Keulen)
2. After about 20 kilometers, change to the E314 (A2) Leuven – Genk – Hasselt
3. After about 500 metres, take the exit 15 Leuven
4. Follow the Boudewijnlaan street (N264) until the 3rd traffic lights, where you turn right at the Celestijnenlaan street.
5. Follow the Celestijnenlaan street, until the 2nd road on the right (after about 200 metres). This is the Kapeldreef street, you’ll find us at the building of I&I Leuven at the end of the street. You can park your car at the front, left, or back side of the building.

By train:
Leuven is a stop on the international railroad London (UK) – Brussels – Liège – Köln (Germany).
Coming from any other line, you can change at Brussels’ North, Central or Midi stations, where there is a train to Leuven every 30 minutes.
Brussels International airport has its own railway station located in the airport building. You can take a direct train from the airport to Leuven.
For more information on the train schedules, go to www.nmbs.be

By bus:
From Leuven station or downtown Leuven, bus 2 (Campus) will bring you to the bus stop of Heverlee Campus Arenberg. The bus stop is situated just opposite to the IMEC campus. You’ll find Pepric at the building of I&I Leuven at the end of the Kapeldreef street, 5-10 minutes walk from the bus stop.
For more information on buses, visit www.delijn.be, the website of the Flemish bus company.