Magnetic Particle Imaging: Monitoring CAR-T cell therapies as they home and kill tumors using safe superferromagnetic nanoparticle tracers (and more!): Nano Seminar series

Prof. Steve Conolly, UC Berkeley, BioE & EECS
Magnetic Particle Imaging (MPI) is an emerging noninvasive biomedical imaging modality that shows great promise for vascular and cellular imaging. MPI uses different physics from all conventional imaging modalities. MPI offers ideal “positive’’ tracer contrast, because human tissues produce zero MPI signal and tissue is magnetically transparent. The signal comes only from superparamagnetic iron oxide tracers (25-nm SPIOs).
MPI has very high molar sensitivity because the SPIO magnetization is 51 million times stronger than the nuclear magnetization, M0, imaged in a 3.0T MRI. Indeed, we can even detect 1 micromolar concentrations in seconds with quantitative, linear, and positive contrast. MPI technology has not reached its true physics limit; we believe MPI could soon achieve single-cell sensitivity and 100-micron resolution with optimized tracers.
MPI applications today already compete with Nuclear Medicine studies on dose-limited sensitivity. But MPI offers a zero-radiation option for: tracking; Pulmonary Embolism detection; Capillary-level noninvasive CBV & CBF for stroke or traumatic brain injury, or to rule out a traumatic gut bleed. Cancer MPI is more challenging but soon could provide a noninvasive screening alternative to X-ray mammography for high-risk women with radiologically dense breast tissue. We recently showed that antibody labeled SPIOs can track WBCs. WBC-MPI could emerge to be the best method to image infection, inflammation, or cancer, and a powerful tool for optimizing immunotherapies. An important advantage relative to scintigraphy GI bleed and V/Q studies (which can take up to 3 hours including prep and scan) is speed: the targeted magnetic tracers can be safely injected immediately from the refrigerator providing first scans in just a few minutes. A crucial advantage of WBC-MPI is zero radioactivity of the tracers. CAR-T and CAR-NK cell therapies cannot survive the radiation dose of In-111 and so you cannot use standard nuclear medicine tools to track these exciting immunotherapies. Indeed, Immuno- MPI could soon become medicine’s most powerful tool for optimizing immunotherapies.
Our lab has recently developed a potential breakthrough in MPI that already shows dramatic SNR and spatial resolution dramatically (10-fold for SNR and linear resolution). Experiments and physical models show that chained SPIOs act like ferromagnetic particles, with remanence and coercivity. This is well-modeled as a positive, regenerative feedback control system– akin to Schmitt Trigger comparators. Moreover, the new tracers show enormous improvements in SNR and spatial resolution, allowing for up to 1000-fold reduction in voxel volume. Our new tracers are not superparamagnetic (SPIO); they are actually superferromagnetic particles. We will show that superferromagnetic tracers could remove the final obstacle to human MPI, allowing for safe 1mm resolution in a human MPI scanner with cost comparable to a conventional MRI scanner.
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Steve Conolly did his PhD and postdoc in EE at Stanford but moved to BioE here at UC Berkeley (yay) in 2004, taking on several leadership roles including chairing the joint UCB/UCSF graduate group. Numerous inventor awards followed.