Molecular Imaging & Image-Guided Therapy

Chemical/Medical Technology

Technical innovations are at the heart of our scientific efforts. We pursue such innovations from the ground up and explore complementary chemical and engineering pathways. Over the years we have utilized our laboratory facilities to design custom chemical entities that facilitate specific disease targeting and cell-functionalization strategies. In these approaches we make use of small molecules, peptides, proteins and/or nanoparticles. In parallel we have been designing and prototyping complementary detection modalities. Technologies that have been realized via hard- and soft-ware engineering efforts.

All our technological designs are driven by a two-way interaction between end-users (MD’s and industry) and scientists/technology developers. As such, we are able to collaboratively invent products that accurately balance “needs” and “possibilities”. By adhering to this strategy many of our technologies have been translated to clinical use and have even made it to routine clinical care viz. ICG-^99mTc-nanocolloid and the miniaturized DROP-IN gamma probe.

Given the complexity of the human anatomy, one of our trade-marks is the incorporation of multiplexing abilities (meaning the integrated detection of different (imaging) signatures) in our technological innovations. Examples are the integrated use of radio- and fluorescent-labels (e.g., via bimodal or hybrid tracers and detectors) and the simultaneous employment of different fluorescent emissions (e.g., via fluorescence multiplexing). Alternative multiplexing routes are pursued through the theranostic integration of imaging and therapeutic strategies.

Technological impact assessment – image-guided interventions

As we develop technologies with the intent to positively impact healthcare, it is critical to assess how technologies reflect on the treatment received by the patient and the treatment provided by the medical professional . In essence this provides three measures for impact: 1) disease outcome, 2) number of complications, and 3) performance enhancement. Where the first two are long term measures that require extensive clinical follow up, the last measure can provide relatively short term feedback. Critically the latter can also be used to refine the design process of new chemical/medical technologies and as such helps strengthen the translational pipeline.

Building on our clinical trials in image-guided surgery, which started as early as 2009, together with i.e., our key clinical partners at the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, we have access to a wealth of long-term outcome data. This allows us to define how our image-guided surgery technologies reflect on the oncological outcome of patients and how they relate to surgical complications. For example, we have gathered evidence that ICG-^99mTc-nanocolloid and ^99mTc-PSMA I&S can improve outcomes, without causing a rise in complications.

To complement performance measures such as lesion detection rates, false positive, and false negative rates, we have started to use multiparametric kinematic analysis. Meaning we use digitized instrument movements to quantify how innovative image guidance approaches reflect on the surgical workflow. Not only does this approach enable us to identify how an imaging strategy alters surgical decision making, it also allows us to identify improvements in the surgical dexterity. Concepts that have thus far helped elucidate the relation between signal to background ratios and surgical decision making and the relation between modality design and surgical dexterity. Features that we use to come up with new chemical and engineering design strategies. At the same time, we see that some clinical experts actually underperform when applying high-end guidance technologies, a finding that warrants the initiation of technology specific surgical training programs.

Cell tracking for infectious diseases

Founded from our origins in the design of biomarker specific tracers, we set-out to explore cell-functionalization strategies. Here our aim is to support the implementation of game changing cell-based therapies. Vaccines for infectious diseases of global importance, amongst which malaria, is one of the key applications that we pursue herein (collaboration with prof. Meta Roestenberg; leiden University Center for Infectious Diseases LU-CID).

Using unique chemical strategies, we essentially ‘hijack’ live cells and alter their therapeutic function. Our role in these efforts revolves around the chemical modification of cells to allow for: 1) functionalization via, e.g., pre-targeting, 2) image-guided delivery, and 3) enhanced therapeutic potency. For example, we use molecular imaging strategies and matching image processing software to elucidate the skin- invasion and subsequent whole-body biodistribution of malaria parasites, cercaria, and hookworms. Subsequently, the biological insights (i.e., biodistribution and kinematics) obtained from these studies are being used to come up with innovative new vaccine designs. In these designs we explore a.o. supramolecular functionalization strategies to load live-attenuated parasites with a combination of diagnostic and therapeutic labels that trigger a controlled immune response.