The frontiers of bioimaging are currently being pushed toward the integration and correlation of several modalities to tackle biomedical research questions holistically and across multiple scales. Correlated Multimodal Imaging (CMI) gathers information about exactly the same specimen with two or more complementary modalities that—in combination—create a composite and complementary view of the sample (including insights into structure, function, dynamics and molecular composition). CMI allows to describe biomedical processes within their overall spatio-temporal context and gain a mechanistic understanding of cells, tissues, diseases or organisms by untangling their molecular mechanisms within their native environment. The two best-established CMI implementations for small animals and model organisms are hardware-fused platforms in preclinical imaging (Hybrid Imaging) and Correlated Light and Electron Microscopy (CLEM) in biological imaging. Although the merits of Preclinical Hybrid Imaging (PHI) and CLEM are well-established, both approaches would benefit from standardization of protocols, ontologies and data handling, and the development of optimized and advanced implementations. Specifically, CMI pipelines that aim at bridging preclinical and biological imaging beyond CLEM and PHI are rare but bear great potential to substantially advance both bioimaging and biomedical research. CMI faces three main challenges for its routine use in biomedical research: (1) Sample handling and preparation procedures that are compatible across modalities without compromising data quality, (2) soft- and hardware solutions to relocate the same region of interest (ROI) after transfer between imaging platforms including fiducial markers, and (3) automated software solutions to correlate complex, multiscale, multimodal and volumetric image data including reconstruction, segmentation and visualization. This review goes beyond preclinical imaging and puts accessible information into a broader imaging context. We present a comprehensive overview of the field of CMI from preclinical hybrid imaging to correlative microscopy, highlight requirements for optimization and standardization, present a synopsis of current solutions to challenges of the field and focus on current efforts to bridge the gap between preclinical and biological imaging (from small animals down to single cells and molecules). The review is in line with major European initiatives, such as COMULIS (CA17121), a COST Action to promote and foster Correlated Multimodal Imaging in Life Sciences.

Protein phosphorylation is known to play an important role in various cellular processes such as cell division, metabolism, survival and apoptosis. It is driven by specific enzymes, tyrosine and serine-threonine protein kinases. Human protein kinases constitute a complicated system with intricate internal and external interactions. The complexity and sophistication of the system implies its vulnerability. Alterations in functions of these enzymes may launch series of pathological changes within the cell and as a result cause diseases. Protein kinases have been shown to be involved in various pathological processes, first of all malignancies. Deregulation of different protein kinases has been found in chronic myelogenous leukaemia, gastrointestinal stromal tumours, various other sarcomas and cancers as well as non-malignant disorders. Therefore, they are regarded as important effectors in human pathology and represent prospective therapeutic targets.

Magnetite (Fe₃O₄) nanoparticles with uniform sizes of 10, 20, and 31 nm were prepared by thermal decomposition of Fe(III) oleate or mandelate in a high-boiling point solvent (>320 °C). To render the particles with hydrophilic and antifouling properties, their surface was coated with a PEG-containing bisphosphonate anchoring group. The PEGylated particles were characterized by a range of physicochemical methods, including dynamic light scattering, transmission electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, and magnetization measurements. As the particle size increased from 10 to 31 nm, the amount of PEG coating decreased from 28.5 to 9 wt.%. The PEG formed a dense brush-like shell on the particle surface, which prevented particles from aggregating in water and PBS (pH 7.4) and maximized the circulation time in vivo. Magnetic resonance relaxometry confirmed that the PEG-modified Fe₃O₄ nanoparticles had high relaxivity, which increased with increasing particle size. In the in vivo experiments in a mouse model, the particles provided visible contrast enhancement in the magnetic resonance images. Almost 70% of administrated 20-nm magnetic nanoparticles still circulated in the blood stream after four hours; however, their retention in the tumor was rather low, which was likely due to the antifouling properties of PEG.

In this report, monodisperse upconversion NaYF₄:Yb³⁺/Er³⁺ nanoparticles with superior optical properties were synthesized by the oleic acid-stabilized high-temperature co-precipitation of lanthanide chlorides in octadec-1-ene as a high-boiling organic solvent. To render the particles with biocompatibility and colloidal stability in bioanalytically relevant phosphate buffered saline (PBS), they were modified by using in-house synthesized poly(ethylene glycol)-neridronate (PEG-Ner), a bisphosponate. The NaYF₄:Yb³⁺/Er³⁺@PEG nanoparticles showed excellent long-term stability in PBS and/or albumin without any aggregation or morphology transformation. The in vitro cytotoxicity of the nanoparticles was evaluated using primary fibroblasts (HF) and a cell line derived from human cervical carcinoma (HeLa). The particles were subsequently modified by using Bolton–Hunter-hydroxybisphosphonate to enable radiolabeling with ¹²⁵I for single-photon emission computed tomography/computed tomography (SPECT/CT) bimodal imaging to monitor the biodistribution of the nanoparticles in non-tumor mice. The bimodal upconversion ¹²⁵I-radiolabeled NaYF₄:Yb³⁺/Er³⁺@PEG nanoparticles are prospective for near-infrared (NIR) photothermal/photodynamic and SPECT/CT cancer theranostics.