Nuclear Imaging of Endogenous Markers of Lymphocyte Response

Coronavirus Disease 2019 (COVID-19) has been a pandemic challenge for the last year. Cardiovascular disease is the most described comorbidity in COVID-19 patients, and it is related to the disease severity and progression. COVID-19 induces direct damage on cardiovascular system, leading to arrhythmias and myocarditis, and indirect damage due to endothelial dysfunction and systemic inflammation with a high inflammatory burden. Indirect damage leads to myocarditis, coagulation abnormalities and venous thromboembolism, Takotsubo cardiomyopathy, Kawasaki-like disease and multisystem inflammatory syndrome in children. Imaging can support the management, assessment and prognostic evaluation of these patients. Ultrasound is the most reliable and easy to use in emergency setting and in the ICU as a first approach. The focused approach is useful in management of these patients due its ability to obtain quick and focused results. This tool is useful to evaluate cardiovascular disease and its interplay with lungs. However, a detailed echocardiography evaluation is necessary in a complete assessment of cardiovascular involvement. Computerized tomography is highly sensitive, but it might not always be available. Cardiovascular magnetic resonance and nuclear imaging may be helpful to evaluate COVID-19-related myocardial injury, but further studies are needed. This review deals with different modalities of imaging evaluation in the management of cardiovascular non-ischaemic manifestations of COVID-19, comparing their use in emergency and in intensive care.

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The Design and Preclinical Evaluation of a Single-Label Bimodal Nanobody Tracer for Image-Guided Surgery

Biomolecules ◽

10.3390/biom11030360 ◽

2021 ◽

Vol 11 (3) ◽

pp. 360

Author(s):

Pieterjan Debie ◽

Noemi B. Declerck ◽

Danny van Willigen ◽

Celine M. Huygen ◽

Bieke De Sloovere ◽

...

Keyword(s):

Single Molecule ◽

Gamma Ray ◽

Nuclear Imaging ◽

Primary Amines ◽

Resection Margins ◽

Fluorescent Light ◽

Single Structure ◽

Fluorescence Images

Intraoperative guidance using targeted fluorescent tracers can potentially provide surgeons with real-time feedback on the presence of tumor tissue in resection margins. To overcome the limited depth penetration of fluorescent light, combining fluorescence with SPECT/CT imaging and/or gamma-ray tracing has been proposed. Here, we describe the design and preclinical validation of a novel bimodal nanobody-tracer, labeled using a “multifunctional single attachment point” (MSAP) label, integrating a Cy5 fluorophore and a diethylenetriaminepentaacetic acid (DTPA) chelator into a single structure. After conjugation of the bimodal MSAP to primary amines of the anti-HER2 nanobody 2Rs15d and 111In-labeling of DTPA, the tracer’s characteristics were evaluated in vitro. Subsequently, its biodistribution and tumor targeting were assessed by SPECT/CT and fluorescence imaging over 24 h. Finally, the tracer’s ability to identify small, disseminated tumor lesions was investigated in mice bearing HER2-overexpressing SKOV3.IP1 peritoneal lesions. [111In]In-MSAP.2Rs15d retained its affinity following conjugation and remained stable for 24 h. In vivo SPECT/CT and fluorescence images showed specific uptake in HER2-overexpressing tumors with low background. High tumor-to-muscle ratios were obtained at 1h p.i. and remained 19-fold on SPECT/CT and 3-fold on fluorescence images over 24 h. In the intraperitoneally disseminated model, the tracer allowed detection of larger lesions via nuclear imaging, while fluorescence enabled accurate removal of submillimeter lesions. Bimodal nuclear/fluorescent nanobody-tracers can thus be conveniently designed by conjugation of a single-molecule MSAP-reagent carrying a fluorophore and chelator for radioactive labeling. Such tracers hold promise for clinical applications.

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Investigating vascular diseases in people living with HIV by nuclear imaging

Journal of Nuclear Cardiology ◽

10.1007/s12350-021-02613-x ◽

2021 ◽

Author(s):

Phillip Chan ◽

Serena Spudich

Keyword(s):

Nuclear Imaging ◽

Vascular Diseases ◽

People Living With Hiv ◽

Living With Hiv

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Site-Specific Dual-Labeling of a VHH with a Chelator and a Photosensitizer for Nuclear Imaging and Targeted Photodynamic Therapy of EGFR-Positive Tumors

Cancers ◽

10.3390/cancers13030428 ◽

2021 ◽

Vol 13 (3) ◽

pp. 428

Author(s):

Emma Renard ◽

Estel Collado Camps ◽

Coline Canovas ◽

Annemarie Kip ◽

Martin Gotthardt ◽

...

Keyword(s):

Photodynamic Therapy ◽

Fluorescence Imaging ◽

Ex Vivo ◽

Growth Factor Receptor ◽

Nuclear Imaging ◽

A431 Cells ◽

Site Specific ◽

Variable Domains ◽

Diagnostic Probe

Variable domains of heavy chain only antibodies (VHHs) are valuable agents for application in tumor theranostics upon conjugation to both a diagnostic probe and a therapeutic compound. Here, we optimized site-specific conjugation of the chelator DTPA and the photosensitizer IRDye700DX to anti-epidermal growth factor receptor (EGFR) VHH 7D12, for applications in nuclear imaging and photodynamic therapy. 7D12 was site-specifically equipped with bimodal probe DTPA-tetrazine-IRDye700DX using the dichlorotetrazine conjugation platform. Binding, internalization and light-induced toxicity of DTPA-IRDye700DX-7D12 were determined using EGFR-overexpressing A431 cells. Finally, ex vivo biodistribution of DTPA-IRDye700DX-7D12 in A431 tumor-bearing mice was performed, and tumor homing was visualized with SPECT and fluorescence imaging. DTPA-IRDye700DX-7D12 was retrieved with a protein recovery of 43%, and a degree of labeling of 0.56. Spectral properties of the IRDye700DX were retained upon conjugation. 111In-labeled DTPA-IRDye700DX-7D12 bound specifically to A431 cells, and they were effectively killed upon illumination. DTPA-IRDye700DX-7D12 homed to A431 xenografts in vivo, and this could be visualized with both SPECT and fluorescence imaging. In conclusion, the dichlorotetrazine platform offers a feasible method for site-specific dual-labeling of VHH 7D12, retaining binding affinity and therapeutic efficacy. The flexibility of the described approach makes it easy to vary the nature of the probes for other combinations of diagnostic and therapeutic compounds.

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