Details

Autor(en) / Beteiligte

• Stroet, Marcus C. M.
• de Blois, Erik
• Stuurman, Debra C.
• de Ridder, Corrina M. A.
• Haeck, Joost
• Seimbille, Yann
• Mezzanotte, Laura
• de Jong, Marion
• Löwik, Clemens W. G. M.
• Panth, Kranthi M.

Titel

In Vivo Evaluation of Indium-111–Labeled 800CW as a Necrosis-Avid Contrast Agent

Ist Teil von

• Molecular imaging and biology, 2020-10, Vol.22 (5), p.1333-1341

Ort / Verlag

Cham: Springer International Publishing

Erscheinungsjahr

2020

Quelle

SpringerLink

Beschreibungen/Notizen

• Purpose Current clinical measurements for tumor treatment efficiency rely often on changes in tumor volume measured as shrinkage by CT or MRI, which become apparent after multiple lines of treatment and pose a physical and psychological burden on the patient. Detection of therapy-induced cell death in the tumor can be a fast measure for treatment efficiency. However, there are no reliable clinical tools for detection of tumor necrosis. Previously, we studied the necrosis avidity of cyanine-based fluorescent dyes, which suffered long circulation times before tumor necrosis could be imaged due to low hydrophilicity. We now present the application of radiolabeled 800CW, a commercially available cyanine with high hydrophilicity, to image tumor necrosis in a mouse model. Procedures We conjugated 800CW to DOTA via a PEG linker, for labeling with single-photon emission-computed tomography isotope indium-111, yielding [ 111 In]In-DOTA-PEG 4 -800CW. We then investigated specific [ 111 In]In-DOTA-PEG 4 -800CW uptake by dead cells in vitro , using both fluorescence and radioactivity as detection modalities. Finally, we investigated [ 111 In]In-DOTA-PEG 4 -800CW uptake into necrotic tumor regions of a 4T1 breast tumor model in mice. Results We successfully prepared a precursor and developed a reliable procedure for labeling 800CW with indium-111. We detected specific [ 111 In]In-DOTA-PEG 4 -800CW uptake by dead cells, using both fluorescence and radioactivity. Albeit with a tumor uptake of only 0.37%ID/g at 6 h post injection, we were able to image tumor necrosis with a tumor to background ratio of 7:4. Fluorescence and radioactivity in cryosections from the dissected tumors were colocalized with tumor necrosis, confirmed by TUNEL staining. Conclusions [ 111 In]In-DOTA-PEG 4 -800CW can be used to image tumor necrosis in vitro and in vivo . Further research will elucidate the application of [ 111 In]In-DOTA-PEG 4 -800CW or other radiolabeled hydrophilic cyanines for the detection of necrosis caused by chemotherapy or other anti-cancer therapies. This can provide valuable prognostic information in treatment of solid tumors.