Fab(nimotuzumab)-HYNIC-99mTc: Antibody Fragmentation for Molecular Imaging Agents

Abstract

Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer.

Preparation and preliminary bioevaluation studies of 68Ga‐NOTA‐rituximab fragments as radioimmunoscintigraphic agents for non‐Hodgkin lymphoma

“…5,6 A detailed literature survey on immuno-PET/SPECT imaging agents demonstrates the magnitude of work carried out in this direction. MAb fragments labeled with radioisotopes such as 99m Tc, 64 Cu, and 111 In [7][8][9][10][11] have been evaluated for their potential applications in the diagnosis of various cancers. [7][8][9][10][11] In this regard, Tang et al reported that 99m Tc-HYNIC-trastuzumab-Fab allowed imaging as early as 2 hours and more clearly at 6 and 24-hour postinjection, thereby permitting imaging of breast tumors within the useful lifetime of 99m Tc.…”

“…MAb fragments labeled with radioisotopes such as 99m Tc, 64 Cu, and 111 In [7][8][9][10][11] have been evaluated for their potential applications in the diagnosis of various cancers. [7][8][9][10][11] In this regard, Tang et al reported that 99m Tc-HYNIC-trastuzumab-Fab allowed imaging as early as 2 hours and more clearly at 6 and 24-hour postinjection, thereby permitting imaging of breast tumors within the useful lifetime of 99m Tc. 8 In similar lines, 64 Cu-labeled Fab fragment of ALT-836 ( 64 Cu-NOTA-ALT-836-Fab), a chimeric antihuman tissue factor MAb, showed fast tumor uptake and good tissue/muscle ratios on immuno-PET imaging of triple negative breast cancer patients performed on the same day.…”

Development and Evaluation of a Novel Radiotracer 125I-rIL-27 to Monitor Allotransplant Rejection by Specifically Targeting IL-27Rα

“…The cytokine was a small ligand of the cytokine receptor that was expressed on the surface of effector cells [47]. Many radio cytokine probes have already been applied in target imaging [48][49][50][51].…”

Hormona liberadora de la hormona luteinizante (LHRH): potencial agente de oncología molecular

“…Hay que tomar en cuenta que el radionucléido 99m Tc se encuentra ampliamente disponible en centros de Medicina Nuclear, posee una química bien establecida y adecuadas propiedades nucleares ([t ½ = 6,04 h, Eγ = 140 KeV (89%)]; lo que junto a su bajo costo lo hacen un radionucleido indicado para la síntesis de este tipo de agentes de imagen. La química del marcado, con 99m Tc de forma directa o a través de agentes quelantes bifuncionales está bien establecida (28,29) y ha sido de amplio uso en nuestro departamento, donde disponemos de una plataforma ya establecida para la generación de este tipo de agentes de imagen (30)(31)(32)(33)(34).…”