- Liam A. McDonnell (1)
- Greet Bemmel van (1)
- Tessa Buckle (1)
- Anton Bunschoten (2)
- Aldrik H. Velders (3)
- Ruud J.B. Peters (1)
- Stijn J.M. Malderen Van (1)
- Wiep Klaas Smits (1)
- Frits Koning (1)
- Joeri Kuil (1)
- Mick M. Welling (2)
- Larissa Müller (1)
- Meta Roestenberg (2)
- Henk Scheper (1)
- Vincent Van Unen (1)
- Steffen Van Wal Der (1)
- Frank Vanhaeke (1)
- Albertus W. Hensbergen (2)
- Fijs W.B. Leeuwen van (2)
- Fijs W.B. Leeuwen Van (1)
Fluorescent imaging of bacterial infections and recent advances made with multimodal radiopharmaceuticals
Welling, Mick M. ; Hensbergen, Albertus W. ; Bunschoten, Anton ; Velders, Aldrik H. ; Scheper, Henk ; Smits, Wiep Klaas ; Roestenberg, Meta ; Leeuwen, Fijs W.B. van - \ 2019
Clinical and Translational Imaging 7 (2019)2. - ISSN 2281-5872 - p. 125 - 138.
Bacterial infection - Fluorescence imaging - Infectious diseases - Molecular imaging - Radioactivity
Background: Today, both radioactive SPECT and PET imaging radiopharmaceuticals are used for clinical diagnosis of bacterial infections. Due to the possible applications in image-guided surgery, fluorescent imaging of infections has gained interest. We here present the highlights and recent developments in the use of fluorescence imaging for bacterial infections. In this overview, we also include the latest developments in multimodal bacterial imaging strategies that combine radioactive and fluorescent imaging. Based on this literature, we present our future perspectives for the field including the translational potential. Methods: In the current review, we complement earlier reports with the most recent fluorescent and multimodal radiopharmaceuticals for bacterial infection imaging. Where possible, in this review, the chemical structure of the compounds and clinical images were shown. Results: A total of 35 out of 77 original articles on pre-clinical and clinical imaging of bacterial infections with fluorescent tracers and multimodality radiopharmaceuticals were included for reviewing. Conclusion: In our view, the highest translational potential lies with compounds that are based on targeting vectors that are specific for bacteria: e.g., fluorescently labelled UBI 29–41 , polymyxin B, vancomycin, ZnDPA and a M. tuberculosis-specific β-lactamase-cleavable linker CNIP800. Multimodal concepts using dually labelled UBI 29–41 , vancomycin, and ZnDPA help connect optical imaging to the more traditional use of radiopharmaceuticals in infectious diseases. Multimodal bacterial imaging is a promising strategy not only to diagnose bacterial infections but also to evaluate the effectivity of surgical treatment for infections.
An update on radiotracer development for molecular imaging of bacterial infections
Welling, Mick M. ; Hensbergen, Albertus W. ; Bunschoten, Anton ; Velders, Aldrik H. ; Roestenberg, Meta ; Leeuwen, Fijs W.B. van - \ 2019
Clinical and Translational Imaging 7 (2019)2. - ISSN 2281-5872 - p. 105 - 124.
Infectious diseases - Molecular imaging - Nuclear medicine - Pathogens - Radiotracers
Background: Bacterial infections are still a major global healthcare problem. To combat the increasing antimicrobial resistance, early diagnosis of bacterial infections—including the identification of bacterial species—is needed to improve antibiotic stewardship and to help reduce the use of broad-spectrum antibiotics. To aid successful targeted antibiotic treatment, specific detection and localisation of infectious organisms is warranted. Nuclear medicine imaging approaches have been successfully used to diagnose bacterial infections and to differentiate between pathogen induced infections and sterile inflammatory processes. Aim: In this comprehensive review we present an overview of recent developments in radiolabelled bacterial imaging tracers. Methods: The PubMed/MEDLINE and Embase (OvidSP) literature databases were systematically searched for publications on SPECT and PET on specific imaging of bacterial using specific guidelines with MeSH-terms, truncations, and completion using cross-references. Tracers in literature that was extensively reviewed before 2016 were not included in this update. Where possible, the chemical structure of the radiolabelled compounds and clinical images were shown. Results: In 219 original articles pre-clinical and clinical imaging of bacterial infection with new tracers were included. In our view, the highest translational potential lies with tracers that are specific to target the pathogens: e.g., 99m Tc- and 68 Ga-labelled UBI 29–41 , 99m Tc-vancomycin, m-[ 18 F]-fluoro-PABA, [methyl- 11 C]-D-methionine, [ 18 F]-FDS, [ 18 F]-maltohexaose and [ 18 F]-maltotriose. An encouraging note is that some of these tracers have already been successfully evaluated in clinical settings. Conclusion: This review summarises updates in tracer development for specific (pre-clinical and clinical) imaging of bacterial infections. We propsed some promising tracers that are likely to become innovative standards in the clinical setting in the near feature.
Hybrid imaging labels : Providing the link between mass spectrometry-based molecular pathology and theranostics
Buckle, Tessa ; Wal, Steffen Van Der; Malderen, Stijn J.M. Van; Müller, Larissa ; Kuil, Joeri ; Unen, Vincent Van ; Peters, Ruud J.B. ; Bemmel, Greet van; McDonnell, Liam A. ; Velders, Aldrik H. ; Koning, Frits ; Vanhaeke, Frank ; Leeuwen, Fijs W.B. Van - \ 2017
Theranostics 7 (2017)3. - ISSN 1838-7640 - p. 624 - 633.
Bimodal - Fluorescence - LA-ICP-MS imaging - Mass cytometry - Mass spectrometry - Molecular imaging - Molecular pathology - Radioisotopes - SPECT
Development of theranostic concepts that include inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) imaging can be hindered by the lack of a direct comparison to more standardly used methods for in vitro and in vivo evaluation; e.g. fluorescence or nuclear medicine. In this study a bimodal (or rather, hybrid) tracer that contains both a fluorescent dye and a chelate was used to evaluate the existence of a direct link between mass spectrometry (MS) and in vitro and in vivo molecular imaging findings using fluorescence and radioisotopes. At the same time, the hybrid label was used to determine whether the use of a single isotope label would allow for MS-based diagnostics. Methods: A hybrid label that contained both a DTPA chelate (that was coordinated with either 165Ho or 111In) and a Cy5 fluorescent dye was coupled to the chemokine receptor 4 (CXCR4) targeting peptide Ac-TZ14011 (hybrid-Cy5-Ac-TZ4011). This receptor targeting tracer was used to 1) validate the efficacy of (165Ho-based) mass-cytometry in determining the receptor affinity via comparison with fluorescence-based flow cytometry (Cy5), 2) evaluate the microscopic binding pattern of the tracer in tumor cells using both fluorescence confocal imaging (Cy5) and LA-ICP-MS-imaging (165Ho), 3) compare in vivo biodistribution patterns obtained with ICP-MS (165Ho) and radiodetection (111In) after intravenous administration of hybrid-Cy5-Ac-TZ4011 in tumor-bearing mice. Finally, LA-ICP-MS-imaging (165Ho) was linked to fluorescence-based analysis of excised tissue samples (Cy5). Results: Analysis with both mass-cytometry and flow cytometry revealed a similar receptor affinity, respectively 352 ± 141 nM and 245 ± 65 nM (p = 0.08), but with a much lower detection sensitivity for the first modality. In vitro LA-ICP-MS imaging (165Ho) enabled clear discrimination between CXCR4 positive and negative cells, but fluorescence microscopy was required to determine the intracellular distribution. In vivo biodistribution patterns obtained with ICP-MS (165Ho) and radiodetection (111In) of the hybrid peptide were shown to be similar. Assessment of tracer distribution in excised tissues revealed the location of tracer uptake with both LA-ICP-MS-imaging and fluorescence imaging.