BME 695L Lecture 3: Theranostics and Molecular Imaging

What this episode covers

See references below for related reading.3.1      Nanomedical systems – levels of challenges3.1.1    Diagnosis - difficult3.1.2    Therapy – more difficult3.1.3    Both ("Theragnosis") – most difficult!3.2      How theragnostics relates to Molecular Imaging3.2.1    conventional imaging is not very specific3.2.2    types of In-vivo Imaging         3.2.2.1 X-rays, CAT (Computed Axial Tomography) scans         3.2.2.2 MRI (magnetic Resonance Imaging)         3.2.2.3 PET (Positron Emission Tomography) scans3.2.3    "molecular imaging" of nanoparticles in-vivo for diagnostics/monitoring of therapeutics3.3      Engineering nanomedical systems for simultaneous molecular imaging3.3.1    using nanomedical cores for MRI contrast agents3.3.2    difficulties in using PET probes for nanomedical devices3.3.3    using cell-specific probes for molecular imaging of nanomedical devices3.3.4    breaking the "diffraction limit" – new nano-level imaging modalities3.4      Theragnostic nanomedical devices3.4.1    using nanomedical devices to guide separate therapeutic device3.4.2    when might we want to combine diagnostics and therapeutics?3.5      Requirements for specific cell targeting3.5.1    must be cell surface biomarker that at least partially identifies that cell3.5.2    OR a Boolean set of several biomarkers whose composite "signature" identifies a cell3.5.3    OR a set of biomarkers that excludes all other cells3.5.4    challenge – how to "multiplex" a Boolean set of targeting molecules3.6      Consequences of mis-targeting3.6.1    “side effects” to innocent bystander (normal) cells3.6.2    these side effects may be lethal to bystander cells, or they may change the overall state of the patient so that the treatment problem is no longer the same3.6.3    Side effects may be unpredictable and may lead to dangerous non-linear patient responses what are difficult to correct and potentially dangerous or even life threatening3.7      Engineering around the consequences of mis-targeting3.7.1    measure number of good (normal) cells destroyed to eliminate a diseased cell3.7.2    put a weighting factor on the relative “goodness” or “badness” of normal cells and diseased cells3.7.3    example: How many stem cells are you willing to lose to purge tumor cells during a bone marrow transplantation? 3.8      Some ways to lower mis-targeting to non-diseased cells3.8.1    lower numbers of nanoparticles3.8.2    improve specificity of targeting molecules according to what is learned about the identity of the mis-targeted cells3.8.3    if possible, require an AND condition requiring simultaneous presence of two target molecules on the same cells being targeted3.8.4    if necessary, design a non-specific targeting control switch on a secondary non-specific target molecule which inactivates subsequent nanomedical device action (off control switch upon detecting an error in targeting).

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