U-SPECT-BioFluo: an integrated radionuclide, bioluminescence, and fluorescence imaging platform

Background: In vivo bioluminescence, fluorescence, and single-photon emission computed tomography (SPECT) imaging provide complementary information about biological processes. However, to date these signatures are evaluated separately on individual preclinical systems. In this paper, we introduce a fully integrated bioluminescence-fluorescence-SPECT platform. Next to an optimization in logistics and image fusion, this integration can help improve understanding of the optical imaging (OI) results. Methods: An OI module was developed for a preclinical SPECT system (U-SPECT, MILabs, Utrecht, the Netherlands). The applicability of the module for bioluminescence and fluorescence imaging was evaluated in both a phantom and in an in vivo setting using mice implanted with a 4 T1-luc + tumor. A combination of a fluorescent dye and radioactive moiety was used to directly relate the optical images of the module to the SPECT findings. Bioluminescence imaging (BLI) was compared to the localization of the fluorescence signal in the tumors. Results: Both the phantom and in vivo mouse studies showed that superficial fluorescence signals could be imaged accurately. The SPECT and bioluminescence images could be used to place the fluorescence findings in perspective, e.g. by showing tracer accumulation in non-target organs such as the liver and kidneys (SPECT) and giving a semi-quantitative read-out for tumor spread (bioluminescence). Conclusions: We developed a fully integrated multimodal platform that provides complementary registered imaging of bioluminescent, fluorescent, and SPECT signatures in a single scanning session with a single dose of anesthesia. In our view, integration of these modalities helps to improve data interpretation of optical findings in relation to radionuclide images

Nanoparticles reveal Extreme Size-Sorting and Morphologies in Complex Coacervate Superstructures

We here provide detailed insight in self-assembled complex coacervate systems exploiting gold nanoparticles for cryoTEM contrast. Nanoparticle-containing dendrimicelles are formed from fifth-generation dendrimer-encapsulated nanoparticles (DENs) and dendrimer-stabilized nanoparticles (DSNs). The complex coacervate structures self-organize in biconcave thin water layers into size-sorted monolayer superstructures. The embedded nanoparticles are a straightforward tool to visualize dendrimicelles and determine the aggregation number and polydispersity. The superstructure shows extreme size-sorting patterns which, contrary to related systems with higher generation dendrimers, consists not only of dendrimicelles but also much bigger complex coacervate nanoassemblies, such as vesicles.</p

A supramolecular approach for liver radioembolization

Hepatic radioembolization therapies can suffer from discrepancies between diagnostic planning (scout-scan) and the therapeutic delivery itself, resulting in unwanted side-effects such as pulmonary shunting. We reasoned that a nanotechnology-based pre-targeting strategy could help overcome this shortcoming by directly linking pre-interventional diagnostics to the local delivery of therapy. Methods: The host-guest interaction between adamantane and cyclodextrin was employed in an in vivo pre-targeting set-up. Adamantane (guest)-functionalized macro albumin aggregates (MAA-Ad; d = 18 μm) and (radiolabeled) Cy5 and β-cyclodextrin (host)-containing PIBMA polymers (99mTc-Cy50.5CD10PIBMA39; MW ~ 18.8 kDa) functioned as the reactive pair. Following liver or lung embolization with (99mTc)-MAA-Ad or (99mTc)-MAA (controls), the utility of the pre-targeting concept was evaluated after intravenous administration of 99mTc-Cy50.5CD10PIBMA39. Results: Interactions between MAA-Ad and Cy50.5CD10PIBMA39 could be monitored in solution using confocal microscopy and were quantified by radioisotope-based binding experiments. In vivo the accumulation of the MAA-Ad particles in the liver or lungs yielded an approximate ten-fold increase in accumulation of 99mTc-Cy50.5CD10PIBMA39 in those organs (16.2 %ID/g and 10.5 %ID/g, respectively) compared to the control. Pre-targeting with MAA alone was shown to be only half as efficient. Uniquely, for the first time, this data demonstrates that the formation of supramolecular interactions between cyclodextrin and adamantane can be used to drive complex formation in the chemically challenging in vivo environment. Conclusion: The in vivo distribution pattern of the cyclodextrin host could be guided by the pre-administration of the adamantane guest, thereby creating a direct link between the scout-scan (MAA-Ad) and delivery of therapy.</p

Precision surgery:the role of intra-operative real-time image guidance - outcomes from a multidisciplinary European consensus conference

Developments within the field of image-guided surgery are ever expanding, driven by collective involvement of clinicians, researchers, and industry. While the general conception of the potential of image-guided surgery is to improve surgical outcome, the specific motives and goals that drive can differ between the different expert groups. To establish the current and future role of intra-operative image guidance within the field of image-guided surgery a Delphi consensus survey was conducted during the 2(nd) European Congress on Image-guided surgery. This multidisciplinary survey included questions on the conceptual potential and clinical value of image-guided surgery and was aimed at defining specific areas of research and development in the field in order to stimulate further advances towards precision surgery. Obtained results based on questionnaires filled in by 56 panel experts (clinicians: N=30, researchers: N=20 and industry: N=6) were discussed during a dedicated expert discussion session during the conference. The outcome of this Delphi consensus is indicative of the potential improvements offered by image-guided surgery and of the need for further research in this emerging field, that can be enriched by the identification of reliable molecular targets

How molecular imaging will enable robotic precision surgery

Molecular imaging is one of the pillars of precision surgery. Its applications range from early diagnostics to therapy planning, execution, and the accurate assessment of outcomes. In particular, molecular imaging solutions are in high demand in minimally invasive surgical strategies, such as the substantially increasing field of robotic surgery. This review aims at connecting the molecular imaging and nuclear medicine community to the rapidly expanding armory of surgical medical devices. Such devices entail technologies ranging from artificial intelligence and computer-aided visualization technologies (software) to innovative molecular imaging modalities and surgical navigation (hardware). We discuss technologies based on their role at different steps of the surgical workflow, i.e., from surgical decision and planning, over to target localization and excision guidance, all the way to (back table) surgical verification. This provides a glimpse of how innovations from the technology fields can realize an exciting future for the molecular imaging and surgery communities

Nanoparticles reveal Extreme Size-Sorting and Morphologies in Complex Coacervate Superstructures

We here provide detailed insight in self-assembled complex coacervate systems exploiting gold nanoparticles for cryoTEM contrast. Nanoparticle-containing dendrimicelles are formed from fifth-generation dendrimer-encapsulated nanoparticles (DENs) and dendrimer-stabilized nanoparticles (DSNs). The complex coacervate structures self-organize in biconcave thin water layers into size-sorted monolayer superstructures. The embedded nanoparticles are a straightforward tool to visualize dendrimicelles and determine the aggregation number and polydispersity. The superstructure shows extreme size-sorting patterns which, contrary to related systems with higher generation dendrimers, consists not only of dendrimicelles but also much bigger complex coacervate nanoassemblies, such as vesicles.</p