RESUMO
Background and purpose: The discovery of chemical substances with carcinogenic properties has allowed the development of several experimental models of colorectal cancer (CRC). Classically, experimental models of CRC in mice have been evaluated through clinical or serial euthanasia. The present study aims to investigate the role of low endoscopy in the analysis of carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Methods: Thirty C57BL6 mice were divided into two groups: a control group with fifteen animals that underwent rectal instillation of saline solution on day 0 and a carcinogen group with fifteen animals that underwent a 100 mg/kg MNNG rectal instillation on day 0. In both groups, low endoscopies were performed on weeks 4 and 8. We used a validated endoscopic scoring system to evaluate the severity of colitis and colorectal tumor. Euthanasia was carried out at week 12. Results: We observed higher inflammation scores (p <0.001) and a higher number of tumors (p <0.05) in the MNNG group than the control group, both at weeks 4 and 8. A worsening of inflammation scores from the first to the second endoscopy was also noticeable in the MNNG group. There were no bowel perforations related to the procedure, and there was one death in the control group. Conclusion: Low endoscopy in experimental animals allows safe macroscopic evaluation of colorectal carcinogenesis without the need for euthanasia.
Assuntos
Metilnitronitrosoguanidina/toxicidade , Neoplasias Experimentais/induzido quimicamente , Neoplasias Retais/induzido quimicamente , Administração Retal , Animais , Carcinogênese/induzido quimicamente , Carcinogênese/patologia , Colonoscopia/métodos , Feminino , Humanos , Metilnitronitrosoguanidina/administração & dosagem , Camundongos , Neoplasias Experimentais/diagnóstico , Neoplasias Experimentais/patologia , Neoplasias Retais/diagnóstico , Neoplasias Retais/patologia , Reto/diagnóstico por imagem , Reto/efeitos dos fármacos , Reto/patologiaRESUMO
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 99mTc. The derivatizations via a 5'-aminohexyl terminal linker were done at room temperature and under mild buffer conditions. Physicochemical and biological controls for both imaging agents were performed verifying the integrity of the aptamer-conjugates by HPLC. Recognition of melanoma (B16F1) and lymphoma (A20) mouse cell lines by the aptamer was studied using cell binding, flow cytometry and confocal microscopy. Finally, in vivo imaging studies in tumour-bearing mice were performed. The new probes were able to bind to melanoma and lymphoma cell lines in vitro, the in vivo imaging in tumour-bearing mice showed different uptake behaviours showing for the fluorescent conjugate good uptake by B cell lymphoma while the radiolabelled conjugate did not display tumour uptake due to its high extravascular distribution, and both showed rapid clearance properties in tumour-bearing mice.
Assuntos
Aptâmeros de Nucleotídeos/farmacocinética , Moléculas de Adesão Celular/antagonistas & inibidores , Corantes Fluorescentes/farmacocinética , Linfoma/diagnóstico , Melanoma/diagnóstico , Impressão Molecular , Inibidores de Proteínas Quinases/farmacocinética , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Aptâmeros de Nucleotídeos/síntese química , Aptâmeros de Nucleotídeos/química , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Humanos , Estrutura Molecular , Neoplasias Experimentais/diagnóstico , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Receptores Proteína Tirosina Quinases/metabolismo , Relação Estrutura-Atividade , Distribuição TecidualRESUMO
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. METHOD: HYNIC-Ahx-cycMSH4-13 peptide was synthesized on an automated peptide synthesizer and displayed an IC50 of 0.3 nM using B16/F1 cells. The 99mTc/tricine radiolabeled peptide was examined for radiochemical purity, stability and cell binding. In vivo, biodistribution and planar gamma imaging studies were performed in B16/F1 melanoma tumor bearing C57BK mice. RESULTS: 99mTc-HYNIC-Ahx-cycMSH4-13 was obtained with a radiochemical purity > 95%, was stable up to 24 h at room temperature and exhibited high binding and rapid internalization in B16/F1 cells. In vivo biodistribution studies showed a tumor uptake of 4.92 ± 0.92 % ID/g and 2.78 ± 1.48 % ID/g at 2 h and 4 h post injection, respectively. Whole-body clearance was rapid through urinary excretion. The melanoma tumors were clearly visualized by planar gamma imaging. CONCLUSION: 99mTc-HYNIC-Ahx-cycMSH4-13 was shown radiochemically stability and exhibited rapid and selective uptake in melanoma cells and tumors. Imaging studies yielded promising preclinical results, warranting further evaluation of 99mTc-HYNIC-cycMSH analogs as melanoma specific imaging agents.
Assuntos
Caproatos/farmacocinética , Neoplasias Experimentais/diagnóstico , Compostos de Organotecnécio/farmacocinética , Fragmentos de Peptídeos/farmacocinética , alfa-MSH/farmacocinética , Animais , Caproatos/química , Camundongos , Estrutura Molecular , Compostos de Organotecnécio/química , Fragmentos de Peptídeos/química , Distribuição Tecidual , Células Tumorais Cultivadas , alfa-MSH/químicaAssuntos
Adaptação Fisiológica/fisiologia , Neoplasias Pulmonares/diagnóstico , Pulmão/patologia , Neoplasias Experimentais/diagnóstico , Estresse Oxidativo/fisiologia , Condicionamento Físico Animal , Animais , Carcinógenos/toxicidade , Progressão da Doença , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/fisiopatologia , Camundongos , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Fatores de Tempo , Uretana/toxicidadeRESUMO
A d-glucose-MAG(3) derivative was successfully synthesized and radiolabeled in high labeling yield. Biodistribution studies in Ehrlich tumor-bearing mice were performed. This compound showed high accumulation in tumor tissue with high tumor-to-muscle ratio and moderate tumor-to-blood ratio. Thus, d-glucose-MAG(3) is a potential agent for tumor diagnosis.
Assuntos
Química Farmacêutica/métodos , Glucose/química , Neoplasias/diagnóstico , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Mertiatida , Tecnécio/química , Animais , Desenho de Fármacos , Camundongos , Modelos Químicos , Transplante de Neoplasias , Neoplasias/metabolismo , Neoplasias Experimentais/diagnóstico , Solventes/química , Distribuição TecidualRESUMO
The marriage of physics, chemistry and biology at the namometric scale, nanotechnology, is a powerful technology which is predicted to have a large impacto on life sciences and particularly cancer treatment. In the following we will show some examples of applications which has already reached clinical treatments as new ideas which may positively influence the understanding, diagnosis and therapy of cancer.
Assuntos
Nanotecnologia , Neoplasias/terapia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Materiais Biocompatíveis , Meios de Contraste , Diagnóstico por Imagem/métodos , Portadores de Fármacos , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Hipertermia Induzida/métodos , Camundongos , Nanopartículas/administração & dosagem , Nanotecnologia/métodos , Nanotecnologia/tendências , Nanotubos de Carbono , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Neoplasias Experimentais/diagnóstico , Pontos QuânticosRESUMO
We label ovaric growth factor (OGF) with Iodine-131 and probed its distribution in experimental mouse with radiopharmacology, toxicology and genetical test with encouraging results. The next step was its distribution in human volunteers and ovarian cancer. The new radiopharmaco have high concentration in ovarian cancer; that make possible its scan visualization "in vivo" for diagnoses and its internal radiation treatment without collateral or adverse effects in 6 month of follow-up (clinical and laboratorial) of the volunteers and patients in where the new radiopharmaco was probed.
Assuntos
Neoplasias Ovarianas/diagnóstico por imagem , Somatomedinas , Animais , Feminino , Humanos , Radioisótopos do Iodo , Neoplasias Experimentais/diagnóstico , Neoplasias Experimentais/diagnóstico por imagem , Oncogenes , Cintilografia , RatosRESUMO
El anticuerpo monoclonal (AcMo) B2C114, dirigido contra el antígeno carcinoembrionario (CEA) fue conjugado con el anhídrido bicíclico del DTPA (CA-DTPA) usando diferentes relaciones molares CA-DTPA: AcMo desde 1:1 hasta 30:1. Se determinó para cada caso la eficiencia de acoplamiento y el número de moléculas de DTPA por molécula de AcMo. Se realizó la marcación con 111In para todas las relaciones molares CA-DTPA: AcMo y se determinó la pureza radioquímica por cromatografía instantánea en placa delgada (ITLC Gelman SG) y cromatografía en gel (Sephadex G-25). La biodistribución del AcMo marcado en ratones normales Balb/c y en portadores de tumor reactivo (M3), a diferentes horas post-inyección, mostró una acumulación creciente en el tumor al cabo de 72 h, con captación en hígado y riñón. Se observó también que al aumentar la relación molar CA-DTPA se incrementó el porcentaje de radiactividad asociada al riñón, lo cual indicaría una mayor inestabilidad del radiofármaco
Assuntos
Animais , Camundongos , Anticorpos Monoclonais , Antígeno Carcinoembrionário , Índio , Marcação por Isótopo , Biomarcadores Tumorais/análise , Neoplasias Experimentais/diagnóstico , Ácido Pentético , Radioisótopos , Cintilografia/tendências , Camundongos Endogâmicos BALB C/imunologia , Anticorpos Monoclonais/metabolismo , Neoplasias da Mama , Quelantes , Distribuição Tecidual/fisiologia , Índio/farmacocinética , Biomarcadores Tumorais/biossíntese , Neoplasias Experimentais , Neoplasias Experimentais/imunologia , Cintilografia/estatística & dados numéricos , Cintilografia/veterináriaRESUMO
El anticuerpo monoclonal (AcMo) B2C114, dirigido contra el antígeno carcinoembrionario (CEA) fue conjugado con el anhídrido bicíclico del DTPA (CA-DTPA) usando diferentes relaciones molares CA-DTPA: AcMo desde 1:1 hasta 30:1. Se determinó para cada caso la eficiencia de acoplamiento y el número de moléculas de DTPA por molécula de AcMo. Se realizó la marcación con 111In para todas las relaciones molares CA-DTPA: AcMo y se determinó la pureza radioquímica por cromatografía instantánea en placa delgada (ITLC Gelman SG) y cromatografía en gel (Sephadex G-25). La biodistribución del AcMo marcado en ratones normales Balb/c y en portadores de tumor reactivo (M3), a diferentes horas post-inyección, mostró una acumulación creciente en el tumor al cabo de 72 h, con captación en hígado y riñón. Se observó también que al aumentar la relación molar CA-DTPA se incrementó el porcentaje de radiactividad asociada al riñón, lo cual indicaría una mayor inestabilidad del radiofármaco