Targeted-Lymphoma Drug Delivery System Based on the Sgc8-c Aptamer.

Aptamers are emerging as a promising new class of functional nucleic acids because they can specifically bind to any target with high affinity and be easily modified chemically with different pharmacophoric subunits for therapy. The truncated aptamer, Sgc8-c, binds to tyrosine-protein kinase-like 7 receptor, a promising cancer therapeutic target, allowing the recognition of haemato-oncological malignancies, among others. We have previously developed aptamer-drug conjugates by chemical synthesis, hybridizing Sgc8-c and dasatinib, a drug proposed for lymphoma chemotherapy.

Aptamer-Based Immunotheranostic Strategies.

The escape from immune surveillance is a hallmark of cancer progression. The classic immune checkpoint molecules PD-1, PD-L1, CTLA-4, LAG-3, TIM-3 novel ones are part of a sophisticated system of up- and downmodulation of the immune system, which is unregulated in cancer. In recent years, there have been remarkable advances in the development of targeting strategies, focused principally on immunotherapies aiming at blocking those molecules involved in the evasion of the immune system.

In Vivo Evaluation of Sgc8-c Aptamer as a Molecular Imaging Probe for Colon Cancer in a Mouse Xenograft Model.

Recent biotechnological applications in the field of clinical oncology led to the identification of new biomarkers as molecular targets of cancer, and to broad developments in the field of personalized medicine. Aptamers are oligonucleotides (ssDNA or RNA) that are selected to specifically recognize a molecular target with high affinity and specificity. Based on this, new horizons for their use as molecular imaging probes are being explored.

Sequence-dependent structural properties of B-DNA: what have we learned in 40 years?

The structure of B-DNA, the physiological form of the DNA molecule, has been a central topic in biology, chemistry and physics. Far from uniform and rigid, the double helix was revealed as a flexible and structurally polymorphic molecule. Conformational changes that lead to local and global changes in the helix geometry are mediated by a complex choreography of base and backbone rearrangements affecting the ability of the B-DNA to recognize ligands and consequently on its functionality.

T908 Polymeric Micelles Improved the Uptake of Sgc8-c Aptamer Probe in Tumor-Bearing Mice: A Co-Association Study between the Probe and Preformed Nanostructures.

Aptamers are oligonucleotides that have the characteristic of recognizing a target with high affinity and specificity. Based on our previous studies, the aptamer probe Sgc8-c-Alexa647 is a promising tool for molecular imaging of PTK7, which is an interesting biomarker in cancer. In order to improve the delivery of this probe as well as create a novel drug delivery nanosystem targeted to the PTK7 receptor, we evaluate the co-association between the probe and preformed nanostructures.

Metastatic and non-metastatic melanoma imaging using Sgc8-c aptamer PTK7-recognizer.

Melanoma is one of the most aggressive and deadly skin cancers, and although histopathological criteria are used for its prognosis, biomarkers are necessary to identify the different evolution stages. The applications of molecular imaging include the in vivo diagnosis of cancer with probes that recognize the tumor-biomarkers specific expression allowing external image acquisitions and evaluation of the biological process in quali-quantitative ways. Aptamers are oligonucleotides that recognize targets with high affinity and specificity presenting advantages that make them interesting molecular imaging probes.

Sgc8-c Aptamer as a Potential Theranostic Agent for Hemato-Oncological Malignancies.

Aptamers represent an emerging class of oligonucleotides that have the ability to bind ligands with high affinity. Sgc8-c aptamer recognizes PTK7, a member of the catalytically defective receptor protein tyrosine kinase family that is upregulated in various cancers, including hemato-oncological malignancies. Herein, an Sgc8-c-NOTA-radiolabeled probe was prepared for theranostic purpose.

Aptamers in Diagnostic and Molecular Imaging Applications.

The origin of the term diagnostic comes from the Greek word gnosis, meaning "to know." In medicine, a diagnostic can predict the pathology risk, disease status, treatment, and prognosis, even following therapy. An early and correct diagnosis is necessary for an efficient treatment.

Derivatizations of Sgc8-c aptamer to prepare metallic radiopharmaceuticals as imaging diagnostic agents: Syntheses, isolations, and physicochemical characterizations.

Aptamers, oligonucleotides with the capability to bind to a target through non-covalent bonds with high affinity and specificity, have a great number of advantages as scaffold to prepare molecular imaging agents. In this sense, we have performed post-SELEX modifications of a truncated aptamer, Sgc8-c, which bind to protein tyrosine kinase 7 to obtain a specific molecular targeting probe for in vivo diagnosis and in vivo therapy. Herein, we describe the synthetic efforts to prepare conjugates between Sgc8-c and different metallic ions chelator moieties in short times, high purities, and adequate yields.

Development of new PTK7-targeting aptamer-fluorescent and -radiolabelled probes for evaluation as molecular imaging agents: Lymphoma and melanoma in vivo proof of concept.

Aptamers are single-stranded oligonucleotides that recognize molecular targets with high affinity and specificity. Aptamer that selectively bind to the protein tyrosine kinase-7 (PTK7) receptor, overexpressed on many cancers, has been labelled as probes for molecular imaging of cancer. Two new PTK7-targeting aptamer probes were developed by coupling frameworks from the fluorescent dye AlexaFluor647 or the 6-hydrazinonicotinamide (HYNIC) chelator-labelled to Tc.

177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma.

Background: Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF.

Objective: To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma.

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

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.

Microwave-assisted synthesis of HYNIC protected analogue for 99mTc labeled antibody.

We described herein a simple and efficient microwave assisted synthesis of HYNIC analogues. Two different activated esters of HYNIC, the hydrazine protected with a trifluoroacetyl group (5) and the free hydrazine (6) were conjugated to the monoclonal antibody Nimotuzumab. Technetium-99m radiolabeling of Nimotuzumab was achieved with high efficiency using 5 and 6 derivates.

Labeling and Biological Evaluation of (99m)Tc-HYNIC-Trastuzumab as a Potential Radiopharmaceutical for In Vivo Evaluation of HER2 Expression in Breast Cancer.

The amplification of HER2 gene has been described in several tumor types, mainly breast cancer with a subsequent increase in HER2 protein expression. Trastuzumab is a humanized monoclonal antibody that recognizes selectively the HER2 extracellular domain. The objective of the present work was to standardize the conjugation of Trastuzumab with Succinimidyl-hydrazinonicotinamide (HYNIC) and labeling with (99m)Tc to obtain (99m)Tc-HYNIC-Trastuzumab for use as in vivo tracer of the HER2 expression in breast cancer.

[(99m)Tc(CO)(3)]-radiolabeled bevacizumab: in vitro and in vivo evaluation in a melanoma model.

Introduction: Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several tumor types, including melanoma. Bevacizumab, a monoclonal antibody against VEGF, could be used as an imaging tool in preclinical studies.

Objective: To radiolabel bevacizumab with [(99m)Tc(CO)3(OH2)3](+) and evaluate it in vivo and in vitro for melanoma imaging properties.

Synthesis and evaluation of (99m)Tc chelate-conjugated bevacizumab.

Vascular endothelial growth factor (VEGF) is one of the classic factors involved in tumor-induced angiognesis in several solid tumors. Bevacizumab, a monoclonal antibody against VEGF, can be used as an imaging tool in preclinical studies. The aim of this study was to radiolabel Bevacizumab with (99m)Tc and to evaluate in vivo its imaging properties in an adenocarcinoma animal model.

A potencial theranostic agent for EGF-R expression tumors: (177)Lu-DOTA-nimotuzumab.

In this work Nimotuzumab (monoclonal antibody, recognizes the EGF-R) was radiolabeled with (177)Lu as a potential cancer therapy radiopharmaceutical. In-vitro cell binding studies and in-vivo biodistribution and imaging studies were performed to determine the radiochemical stability, targeting specificity and pharmacokinetics of the (177)Lu-labeled antibody. Nimotuzumab was derivatized with DOTA-NHS at room temperature for 2 hours.

Synthesis of 99mTc-nimotuzumab with tricarbonyl ion: in vitro and in vivo studies.

The Epidermal growth factor receptor (EGFR) family plays an important role in carcinogenesis. CIMAher® (Nimotuzumab), is a humanized monoclonal antibody, which recognizes EGFR with high affinity. The aim of this work was to perform the direct labeling of Nimotuzumab with [99mTc(CO)3(H2O)3]+ as precursor and to evaluate its labeling conditions, in vitro and in vivo stability and biodistrution in normal C57 BL/6J mice.