Mulitmodual imaging: new probes for positron emission tomography combined with magnetic resonance or optical imaging
Professor Steve Archibald, University of Hull
The design of multimodal imaging constructs requires consideration of the optimal method to combine components. Targeting to specific tissues or physiological processes introduces a further aspect to the system.
In general two approaches have been taken:
(1) Molecular constructs where components are combined in a stepwise manner allows more exquisite control of the imaging probe formed but can be laborious. This approach is most effective when components are multifunctional (i.e. a combined dye and targeting component). The development of molecular probes that combine positron emission tomography/optical imaging potential will be discussed. The use of molecular properties such as lipophilicity and charge to influence tissue/ cellular uptake and localisation will be exemplified in the determination of mitochondrial function and cell surface receptor targeting in vitro and in vivo.
(2) Nanoparticles and polymers offer opportunity for conjugation of multiple types of imaging or targeting groups on the surface and the core can also have imaging or contrast agent properties. Examples will be presented of the construction of nanoparticles for multimodal imaging in tissue engineering applications.
The design of probes from synthesis and characterisation through to in vivo imaging will be used to validate these approaches and demonstrate the potential for translational studies.
Professor Willem Mulder, Mount Sinai School of Medicine
Nanodrugs are self-assembled assembled structures for which drug loading stability is strongly influenced by the in vivo environment. Interactions between nanodrugs and blood components have been reported to cause drug leakage. Therefore, thoroughly understanding in vivo drug-carrier association stability and dissociation kinetics should improve delivery efficiency and, as a result, therapeutic efficacy. We have recently shown that optical imaging techniques, including Förster resonance energy transfer (FRET) imaging, can monitor the drug-carrier association and help identify key parameters that determine drug-carrier compatibility. These findings can serve as drug delivery efficiency guidelines that can be applied to improve nanodrug design.
Despite nanomedicine’s promise and the field’s research activity, its potential is not being fully met and implementation in clinical care is falling behind. In part this is due to the technology’s immaturity, but – more importantly – ways to stratify patients that may benefit from nanodrug-based therapy are nonexistent. The ability to non-invasively evaluate targeting would greatly improve patient care by allowing swift adjustments in dosage and/or treatment regimen. Strategies in which nanodrugs are labeled for imaging-facilitated delivery are extensively studied. Unfortunately, such theranostic approaches have little clinical relevance.
As has been shown for antibody therapy, an easy-to-prepare companion diagnostic for quantitative imaging of nanodrugs can overcome these issues. Practically, the companion diagnostic can be applied to screen for patient amenability, but can also be used as an agent that is co-injected with the actual nanodrug to aid in treatment continuation decision.
In this presentation, imaging-facilitated optimization of nanodrugs and the “companion diagnostic’ concept, the latest advances in these fields, as well as translational considerations will be discussed.
Professor Chunhua Yan, Peking University
Professor Gary Wong, Hong Kong Baptist University
One of the major limitations of the existing anticancer agents is their differentiation of cancer cells and normal cells. Recently, some studies in the literature have suggested that some overexpressed cancer cell cycle regulating proteins (e.g. Cyclin(s), Plk1 and EBNA1) can be the particular cancer targets. Several small molecules as their inhibitors have been reported; however, those reported inhibitors are not emissive and cannot directly evaluate their effectiveness, such as real time imaging, biodistribution and pharmacokinetic studies. Over the recent two decades, luminescent lanthanide materials have shown extensive applications in the detection of various bioactive molecules and for in vitro/in vivo imaging, addressing the problem of autofluorescence. For this reason, one of our driving forces for synthesizing new lanthanide materials for imaging these cell cycle regulated protein relates to their unique photophysical properties, such as long emission lifetimes (effective elimination of biological auto-fluorescence in time-resolved spectroscopy) and characteristic hypersensitive emissions, (providing real-time information about the effect on coordination environment by surrounding entities, especially with europium) which are attractive substitutes to the more commonly used organic fluorophores.
In this seminar, I would like to share our development recently on emissive lanthanide materials as dual bioprobes for in vitro/in vivo imaging and inhibition of overexpressed tumor regulator proteins, such as Cyclin(s), Plk1 and EBNA1. It is hoped that the success in research could also lead to the success in practice, thereby providing more powerful tools to get more complete pictures of the roles of Cyclin(s)/Plk1/EBNA1.