Molecular Imaging of Melanoma VEGF-expressing Tumors through [Tc]Tc-HYNIC-Fab(Bevacizumab).

Background: Angiogenesis is a process that many tumors depend on for growth, development, and metastasis. Vascular endothelial growth factor (VEGF) is one of the major players in tumor angiogenesis in several tumor types, including melanoma. VEGF inhibition is achieved by bevacizumab, a humanized monoclonal antibody that binds with high affinity to VEGF and prevents its function.

Synthesis of a [F]F Estradiol Derivative via Click Chemistry Using an Automated Synthesis Module: In Vitro Evaluation as Potential Radiopharmaceutical for Breast Cancer Imaging.

"Click reactions" are a very useful tool for the selective conjugation of different molecular subunits to produce complex structures in a simple way. In this paper, we present the application of Cu(I)-catalyzed biorthogonal reactions between alkynes and azides to the indirect radiofluorination of an estradiol derivative with potential applications in estrogen receptor imaging. The procedure was fully developed on an automated synthesis platform, and conditions were optimized to achieve the desired product with a reasonable yield without precipitation.

Enhanced Tumor Targeting of Radiolabeled Mouse/Human Chimeric Anti-Tn Antibody in Losartan-Treated Mice Bearing Tn-Expressing Lung Tumors.

ChiTn, a mouse/human chimeric anti-Tn monoclonal antibody, was radiolabeled with iodine-131 (I) and technetium-99m (Tc) to assess its biodistribution and internalization in Tn-expressing (Tn+) and wild-type (Tn-) LL/2 lung cancer cells. Selective accumulation and gradual internalization of ChiTn were observed in Tn+ cells. Biodistribution in mice with both Tn+ or Tn- lung tumors indicated that the uptake of radiolabeled ChiTn within tumors increased over time.

Mitofusin 1 silencing decreases the senescent associated secretory phenotype, promotes immune cell recruitment and delays melanoma tumor growth after chemotherapy.

Cellular senescence is a therapy endpoint in melanoma, and the senescence-associated secretory phenotype (SASP) can affect tumor growth and microenvironment, influencing treatment outcomes. Metabolic interventions can modulate the SASP, and mitochondrial energy metabolism supports resistance to therapy in melanoma. In a previous report we showed that senescence, induced by the DNA methylating agent temozolomide, increased the level of fusion proteins mitofusin 1 and 2 in melanoma, and silencing Mfn1 or Mfn2 expression reduced interleukin-6 secretion by senescent cells.

Automated prostate multi-regional segmentation in magnetic resonance using fully convolutional neural networks.

Objective: Automatic MR imaging segmentation of the prostate provides relevant clinical benefits for prostate cancer evaluation such as calculation of automated PSA density and other critical imaging biomarkers. Further, automated T2-weighted image segmentation of central-transition zone (CZ-TZ), peripheral zone (PZ), and seminal vesicle (SV) can help to evaluate clinically significant cancer following the PI-RADS v2.1 guidelines.

Radiosynthesis and validation of [ F]fluoroestradiol in a Synthra plus research platform for use in routine clinical practice.

In this practitioner protocol, the optimization of the radiochemical synthesis of [ F]fluoroestradiol (FES) on the Synthra RNplus research automated platform is described in detail and a quality control (QC) summary of three validation productions is presented. In comparison with published synthesis methods developed on other platforms, the yield was considerably improved (40%-45% ndc). The other important improvement is the reduction of the required concentration of H SO avoiding the production of high concentrations of acidic vapors that can deteriorate the module.

Tocilizumab Labeling with 99mTechnetium via HYNIC as a Molecular Diagnostic Agent for Multiple Myeloma.

Background: Multiple myeloma is the second most common hematological malignancy. Interleukin-6 (IL-6) is one of the key molecules related to growth, survival and proliferation of myeloma cells. Tocilizumab is a humanized monoclonal antibody directed against receptor of IL-6.

Technetium-99m- or Cy7-Labeled Rituximab as an Imaging Agent for Non-Hodgkin Lymphoma.

Introduction: Rituximab was the first monoclonal antibody approved for the treatment of B-cell non-Hodgkin lymphoma (NHL) expressing CD20 antigen. This antibody has also the potential to be used as a specific fluorescent and radiolabel agent for targeting NHL.

Objective: To radiolabel rituximab with technetium-99m (99mTc) or Cy7 and evaluate both probes as potential imaging agents for NHL.

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.

The Effect of A Hexanoic Acid Linker Insertion on the Pharmacokinetics and Tumor Targeting Properties of the Melanoma Imaging Agent 99mTc-HYNIC-cycMSH.

Background: Lactam cyclized alpha-melanocyte stimulating hormone (α-MSH) analogues exhibit high stability and affinity for the MC1-R receptors over expressed in melanoma cells. Recently, we reported a novel 99mTc-HYNIC-cycMSH4-13 analogue with the HYNIC chelator directly attached to the lactam cyclized ring.

Objective: In this study we proposed the introduction of a 6-aminohexanoic acid (Ahx) linker between the HYNIC chelator and lactam cyclized peptide cycMSH4-13 to reduce steric hindrance and improve the melanoma targeting and imaging proprieties of the radiolabeled peptide.

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.

Evaluation of tricine and EDDA as Co-ligands for 99mTc-labeled HYNIC-MSH analogs for melanoma imaging.

Several radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs have been studied for their abilities to target melanoma tumor cells through specific recognition and binding to the melanocortin receptor 1 (MCR1). In this work, a lactam bridgecyclized α-MSH analog was labeled with (99m) via the hydrazinonicotinamide (HYNIC) chelator and characterized for its melanoma tumor targeting properties. The bifunctional chelating agent HYNIC-Boc was attached to the N-terminus of the MSH peptide followed by the lactam cyclization, resulting in the HYNIC-cyc-MSH analog.

[99mTc(CO)3]+ and [99mTcO2]+ radiolabeled cyclic melanotropin peptides for melanoma SPECT imaging.

The melanoma targeting peptides (Ala-triazol)Ac-Re(Arg(11))CCMSH and N4-CO-Re(Arg(11))CCMSH were radiolabeled with [(99m)Tc(CO)3](+) and [(99m)TcO2](+), respectively, and examined for in vitro cell binding, in vivo biodistribution and imaging properties. The (Ala-triazol)Ac-Re(Arg(11))CCMSH and N4-CO-Re(Arg(11))CCMSH were synthesized as protected peptides on resin followed by rhenium cyclization with [(C6H5)3P]2ReOCl3 in DMF. The peptides were labeled with (99m)Tc and examined for radiochemical stability and melanoma cell binding.

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.

Imaging astrocytosis with PET in Creutzfeldt-Jakob disease: case report with histopathological findings.

In a previous study, patients with suspect Creutzfeldt-Jakob's disease (CJD) have been examined with Positron Emission Tomography (PET) combining N-[11C-methyl]-L-deuterodeprenyl (DED) and [(18)F] 2- fluorodeoxyglucose (FDG) in an attempt to detect astrocytosis and neuronal dysfunction, two of the hallmarks in CJD. Increased DED uptake with pronounced hypometabolism matching the areas with high DED retention was found in the fronto-parieto-occipital areas and cerebellum of patients with confirmed CJD. However, the temporal lobes did not present such a pattern.

Preparation and primary bioevaluation of 99mTc-labeled-1-thio-β-D-glucose as melanoma targeting agent.

The development of specific radiolabeled probes towards molecular markers in vivo has gained interest as targeted imaging agents for a more accurate detection of diseases. The aim of this study was to evaluate early detection of melanoma tumor based on 1-thio-β-D-glucose (1-TG) radiolabeled with technetium-99m. 99mTc-1-TG has been synthesized and evaluated in vitro and in vivo for melanoma uptake.

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.

Biological evaluation of glucose and deoxyglucose derivatives radiolabeled with [99mTc(CO)3(H2O)3]+ core as potential melanoma imaging agents.

Glucose 9 and 2-deoxyglucose 10 were successfully synthesized and radiolabeled with [(99m)Tc(CO)(3)(H(2)0)(3)](+) intermediate in high yield. The complexes were characterized by HPLC and its stability with histidine over time was challenged. Cell uptake and biodistribution studies in melanoma-bearing C57BL/6 mice were performed.