Mice and men: An antibody conjugate with trans‐cyclooctene was administered to tumor‐bearing mice, and the resulting chemically tagged tumors were subsequently treated with an 111In‐labeled tetrazine ...probe in an inverse‐electron‐demand Diels–Alder reaction. The adduct was formed in a remarkable 52–57 % yield in vivo and used for non‐invasive pretargeted tumor imaging in mice (see picture).
Combining Positron Emission Tomography (PET) with Magnetic Resonance Imaging (MRI) results in a promising hybrid molecular imaging modality as it unifies the high sensitivity of PET for molecular and ...cellular processes with the functional and anatomical information from MRI. Digital Silicon Photomultipliers (dSiPMs) are the digital evolution in scintillation light detector technology and promise high PET SNR. DSiPMs from Philips Digital Photon Counting (PDPC) were used to develop a preclinical PET/RF gantry with 1-mm scintillation crystal pitch as an insert for clinical MRI scanners. With three exchangeable RF coils, the hybrid field of view has a maximum size of 160 mm × 96.6 mm (transaxial × axial). 0.1 ppm volume-root-mean-square B 0-homogeneity is kept within a spherical diameter of 96 mm (automatic volume shimming). Depending on the coil, MRI SNR is decreased by 13% or 5% by the PET system. PET count rates, energy resolution of 12.6% FWHM, and spatial resolution of 0.73 mm 3 (isometric volume resolution at isocenter) are not affected by applied MRI sequences. PET time resolution of 565 ps (FWHM) degraded by 6 ps during an EPI sequence. Timing-optimized settings yielded 260 ps time resolution. PET and MR images of a hot-rod phantom show no visible differences when the other modality was in operation and both resolve 0.8-mm rods. Versatility of the insert is shown by successfully combining multi-nuclei MRI ( 1 H/ 19 F) with simultaneously measured PET ( 18 F-FDG). A longitudinal study of a tumor-bearing mouse verifies the operability, stability, and in vivo capabilities of the system. Cardiac- and respiratory-gated PET/MRI motion-capturing (CINE) images of the mouse heart demonstrate the advantage of simultaneous acquisition for temporal and spatial image registration.
Galectins are carbohydrate binding proteins that function in many key cellular processes. We have previously demonstrated that galectins are essential for tumor angiogenesis and their expression is ...associated with disease progression. Targeting galectins is therefore a potential anti‐angiogenic and anti‐cancer strategy. Here, we used a rational approach to generate antibodies against a specific member of this conserved protein family, i.e. galectin‐1. We characterized two novel mouse monoclonal antibodies that specifically react with galectin‐1 in human, mouse and chicken. We demonstrate that these antibodies are excellent tools to study galectin‐1 expression and function in a broad array of biological systems. In a potential diagnostic application, radiolabeled antibodies showed specific targeting of galectin‐1 positive tumors. In a therapeutic setting, the antibodies inhibited sprouting angiogenesis in vitro and in vivo, underscoring the key function of galectin‐1 in this process.
What's New?
Galectins are carbohydrate‐binding proteins with an essential role in tumor angiogenesis and whose expression is associated with disease progression. Based on a rational approach, here the authors generated and characterized two novel mouse monoclonal antibodies that specifically react with galectin‐1 in human, mouse and chicken. The antibodies are promising tools to study galectin‐1 expression and function in a broad array of biological systems. In a potential diagnostic application, radiolabeled antibodies showed specific targeting of galectin‐1 positive tumors. In a therapeutic setting, the antibodies inhibited sprouting angiogenesis in vitro and in vivo, underscoring the key function of galectin‐1 in this process.
Immuno-PET as a quantitative imaging procedure before or concomitant with radioimmunotherapy is an attractive option to improve confirmation of tumor targeting and especially assessment of radiation ...dose delivery to both tumor and normal tissues. General information about PET, PET systems, and quantification is provided in this review. The requirements for an appropriate positron emitter and characteristics of the most attractive candidate emitters for immuno-PET are discussed. An overview of preclinical and clinical immuno-PET studies reported in the literature is provided.
Fibrin deposition plays an important role in the formation of mature tumor stroma and provides a facilitating scaffold for tumor angiogenesis. This study investigates the potential of the ...111In-labeled fibrin-binding peptide EPep for SPECT imaging of intratumoral fibrin deposition. 111In-EPep and negative control 111In-NCEPep were synthesized and characterized in vitro. In vivo SPECT images and ex vivo biodistribution profiles and autoradiographs were obtained in a fibrin-rich BT-20 breast cancer mouse model. Furthermore, biodistribution profiles were obtained in the fibrin-poor MDA-MD-231 model. In vitro, 111In-EPep displayed significantly more binding than 111In-NCEPep toward human and mouse derived fibrin. SPECT/CT images displayed a marked SPECT signal in the tumor area for BT-20 tumor bearing mice injected with EPep but not for mice injected with NCEPep. Biodistribution profiles of BT-20 tumor bearing mice 3 h post-tracer injection showed significantly higher tumor uptake for EPep with respect to NCEPep (0.39 ± 0.14 and 0.11 ± 0.03% ID g–1, respectively), whereas uptake in other organs was similar for EPep and NCEPep. Autoradiography of BT-20 tumor sections displayed a high signal for EPep which colocalized with intratumoral fibrin deposits. Histological evaluation of MDA-MB-231 tumor sections displayed no significant tumor stroma and only minute fibrin deposits. Biodistribution profiles in MDA-MB-231 tumor bearing mice 3 h post-injection showed EPep tumor uptake (0.14 ± 0.04% ID g–1) which was significantly lower with respect to EPep BT-20 tumor uptake, indicating fibrin-specificity of EPep tumoral uptake. In conclusion, this work demonstrates the potential of EPep SPECT imaging for visualization of tumoral fibrin deposition.
Wie sieht's aus in der Maus? Ein trans‐Cycloocten‐Antikörper‐Konjugat wurde Tumormäusen verabreicht. Die derart chemisch markierten Tumore wurden dann mit einer 111In‐markierten Tetrazin‐Sonde in ...einer Diels‐Alder‐Reaktion mit inversem Elektronenbedarf umgesetzt, die das Addukt in vivo mit einer bemerkenswerten Ausbeute von 52–57 % ergab. Mit diesem nichtinvasiven Verfahren gelang die Abbildung von Tumoren in Mäusen (siehe Bild).
Antibody-PET imaging might be of value for the selection of radioimmunotherapy (RIT) candidates to confirm tumor targeting and to estimate radiation doses to tumor and normal tissues. One of the ...requirements to be set for such a scouting procedure is that the biodistributions of the diagnostic and therapeutic radioimmunoconjugates should be similar. In the present study we evaluated the potential of the positron emitters zirconium-89 ((89)Zr) and iodine-124 ((124)I) for this approach, as these radionuclides have a relatively long half-life that matches with the kinetics of MAbs in vivo (t(1/2) 3.27 and 4.18 days, respectively). After radiolabeling of the head and neck squamous cell carcinoma (HNSCC)-selective chimeric antibody (cMAb) U36, the biodistribution of two diagnostic (cMAb U36-N-sucDf-(89)Zr and cMAb U36-(124)I) and three therapeutic radioimmunoconjugates (cMAb U36-p-SCN-Bz-DOTA-(88)Y-with (88)Y being substitute for (90)Y, cMAb U36-(131)I, and cMAb U36-MAG3-(186)Re) was assessed in mice with HNSCC-xenografts, at 24, 48, and 72 hours after injection. Two patterns of biodistribution were observed, one pattern matching for (89)Zr- and (88)Y-labeled cMAb U36 and one pattern matching for (124)I-, (131)I-, and (186)Re-cMAb U36. The most remarkable differences between both patterns were observed for uptake in tumor and liver. Tumor uptake levels were 23.2 +/- 0.5 and 24.1 +/- 0.7%ID/g for the (89)Zr- and (88)Y-cMAb U36 and 16.0 +/- 0.8, 15.7 +/- 0.79 and 17.1 +/- 1.6%ID/g for (124)I-, (131)I-, and (186)Re-cMAb U36-conjugates, respectively, at 72 hours after injection. For liver these values were 6.9 +/- 0.8 ((89)Zr), 6.2 +/- 0.8 ((88)Y), 1.7 +/- 0.1 ((124)I), 1.6 +/- 0.1 ((131)I), and 2.3 +/- 0.1 ((186)Re), respectively. These preliminary data justify the further development of antibody-PET with (89)Zr-labeled MAbs for scouting of therapeutic doses of (90)Y-labeled MAbs. In such approach (124)I-labeled MAbs are most suitable for scouting of (131)I- and (186)Re-labeled MAbs.
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