RESUMEN
Immuno-PET is a molecular imaging technique utilizing positron emission tomography (PET) to measure the biodistribution of an antibody species labeled with a radioactive isotope. When applied as a clinical imaging technique, an immuno-PET imaging agent must be manufactured with quality standards appropriate for regulatory approval. This paper describes methods relevant to the chemistry, manufacturing, and controls component of an immuno-PET regulatory filing, such as an investigational new drug application. Namely, the production, quality control, and characterization of the immuno-PET clinical imaging agent, ZED8, an 89Zr-labeled CD8-specific monovalent antibody as well as its desferrioxamine-conjugated precursor, CED8, is described and evaluated. PET imaging data in a human CD8-expressing tumor murine model is presented as a proof of concept that the imaging agent exhibits target specificity and comparable biodistribution across a range of desferrioxamine conjugate loads.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Linfocitos T CD8-positivos/inmunología , Leucemia de Células T/diagnóstico por imagen , Imagen Molecular , Tomografía de Emisión de Positrones , Radioisótopos/administración & dosificación , Radiofármacos/administración & dosificación , Circonio/administración & dosificación , Animales , Anticuerpos Monoclonales/química , Línea Celular Tumoral , Femenino , Humanos , Leucemia de Células T/inmunología , Ratones SCID , Valor Predictivo de las Pruebas , Prueba de Estudio Conceptual , Control de Calidad , Radioisótopos/química , Radioisótopos/normas , Radiofármacos/química , Radiofármacos/normas , Circonio/química , Circonio/normasAsunto(s)
Anticuerpos Monoclonales/administración & dosificación , Trasplante de Médula Ósea , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Herpesvirus Humano 4 , Factores Inmunológicos/administración & dosificación , Leucemia de Células T/terapia , Enfisema Mediastínico/tratamiento farmacológico , Anticuerpos Monoclonales de Origen Murino , Preescolar , ADN Viral/sangre , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico por imagen , Humanos , Leucemia de Células T/sangre , Leucemia de Células T/complicaciones , Leucemia de Células T/diagnóstico por imagen , Leucemia de Células T/virología , Masculino , Enfisema Mediastínico/sangre , Enfisema Mediastínico/complicaciones , Enfisema Mediastínico/diagnóstico por imagen , Enfisema Mediastínico/virología , Radiografía , Rituximab , Carga ViralRESUMEN
Adult T cell leukemia/lymphomas are aggressive disorders, which infiltrate not only the bone marrow but extensively the visceral organs as well. A case with left ventricular systolic dysfunction with myocardial infiltration and massive pericardial effusion which was demonstrated with echocardiography is discussed. The patient responded well to pericardial drainage and subsequent chemotherapy. The dramatic improvement in echocardiographic findings after chemotherapy gave a clue to investigate suspected patients with aggressive leukemia and lymphomas for exclusion of leukemic infiltration of myocardium.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Leucemia de Células T/tratamiento farmacológico , Leucemia de Células T/patología , Infiltración Leucémica , Miocardio/patología , Enfermedad Aguda , Adulto , Humanos , Leucemia de Células T/diagnóstico por imagen , Masculino , Inducción de Remisión , Ultrasonografía , Disfunción Ventricular Izquierda/etiologíaRESUMEN
A 77-year-old man developed primary adult T-cell leukemia/lymphoma (ATL) of the bone with osteolytic lesions. A biopsy of the lesion revealed proliferation of atypical, large lymphoid cells with a local increase of osteoclasts. The clonal integration of human T-lymphotropic virus type I proviral DNA revealed the tumor cells to be ATL. They produced macrophage inflammatory protein 1alpha (MIP-1alpha) but not parathyroid hormone-related protein or other osteoclast-activating factors. Because MIP-1 produced by tumor cells enhances the expression of receptor activator of nuclear factor kappaB ligand (RANKL) of local osteoblasts and stromal cells, even of tumor cells, the increase of osteoclasts in the close vicinity of ATL cells was considered to result in local bone destruction.
Asunto(s)
Neoplasias Óseas/patología , Leucemia de Células T/patología , Linfoma/patología , Anciano , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/metabolismo , Proteínas Portadoras/metabolismo , Quimiocina CCL3 , Quimiocina CCL4 , Humanos , Leucemia de Células T/diagnóstico por imagen , Leucemia de Células T/metabolismo , Linfoma/diagnóstico por imagen , Linfoma/metabolismo , Proteínas Inflamatorias de Macrófagos/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Osteólisis/diagnóstico por imagen , Osteólisis/metabolismo , Osteólisis/patología , Proteína Relacionada con la Hormona Paratiroidea/metabolismo , Ligando RANK , Radiografía , Receptor Activador del Factor Nuclear kappa-BAsunto(s)
Neoplasias Cardíacas/diagnóstico , Leucemia de Células T/diagnóstico , Antineoplásicos/uso terapéutico , Asparaginasa/administración & dosificación , Niño , Diagnóstico Diferencial , Ecocardiografía , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/tratamiento farmacológico , Neoplasias Cardíacas/secundario , Humanos , Leucemia de Células T/diagnóstico por imagen , Leucemia de Células T/tratamiento farmacológico , Leucemia de Células T/patología , Masculino , Metástasis de la Neoplasia , Derrame Pericárdico/diagnóstico por imagen , Prednisolona/administración & dosificación , Vincristina/administración & dosificaciónAsunto(s)
Infecciones por Deltaretrovirus/complicaciones , Virus Linfotrópico T Tipo 1 Humano , Leucemia de Células T/virología , Osteítis Fibrosa Quística/etiología , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/etiología , Fémur/diagnóstico por imagen , Peroné/diagnóstico por imagen , Humanos , Leucemia de Células T/diagnóstico por imagen , Leucemia de Células T/fisiopatología , Persona de Mediana Edad , Osteítis Fibrosa Quística/diagnóstico por imagen , Osteítis Fibrosa Quística/fisiopatología , Proteína Relacionada con la Hormona Paratiroidea , Proteínas/metabolismo , Radiografía , Tibia/diagnóstico por imagenAsunto(s)
Ecocardiografía Transesofágica , Leucemia de Células T/diagnóstico por imagen , Infiltración Leucémica , Válvula Mitral/diagnóstico por imagen , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Leucemia de Células T/tratamiento farmacológico , Leucemia de Células T/patología , Persona de Mediana Edad , Válvula Mitral/patología , Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/patologíaRESUMEN
Bone scintigraphy was performed in a 69-year-old male patient with adult T-cell leukemia suffering from right lower limb pain. Numerous sites of increased uptake were seen in the skull, left clavicle, bilateral humeri, bilateral radii and right femur and tibia. Bone radiographs showed multiple osteolytic lesions, most of which corresponded to the abnormal deposits on the bone scans with 740 MBq of 99mTc-hydroxymethylene diphosphonate. This pattern is rarely reported, but bone involvement of adult T-cell leukemia is not uncommon. Bone involvement was remarkable on the appendicular skeleton when compared with common metastatic bone tumors. Bone scintigraphy may be useful in detecting bone involvement in adult T-cell leukemia.
Asunto(s)
Huesos/diagnóstico por imagen , Leucemia de Células T/diagnóstico por imagen , Osteólisis/diagnóstico por imagen , Radiofármacos , Medronato de Tecnecio Tc 99m/análogos & derivados , Anciano , Humanos , Leucemia de Células T/fisiopatología , Masculino , Dolor , Radiofármacos/farmacocinética , Medronato de Tecnecio Tc 99m/farmacocinética , Distribución Tisular , Tomografía Computarizada de EmisiónAsunto(s)
Radioisótopos de Galio , Leucemia de Células T/diagnóstico por imagen , Neoplasias de la Parótida/diagnóstico por imagen , Radiofármacos , Anciano , Humanos , Hipertrofia , Leucemia de Células T/patología , Ganglios Linfáticos/patología , Masculino , Invasividad Neoplásica , Glándula Parótida/patología , Neoplasias de la Parótida/patología , CintigrafíaRESUMEN
Adult T cell leukemia (ATL), a neoplasm of mature helper T lymphocytes is etiologically associated with human T lymphotropic virus type-I (HTLV-I). ATL cells infiltrate various organs, the lung, skin, central nervous system, gastrointestinal tract, and bone, causing various clinical manifestations. Two unusual cases of ATL, in which lytic bone lesion was the primary site of ATL, are described. One patient had multiple lytic lesions in bones without any involvement of other organs, and the other patient had a bone lesion in the right radius, which disappeared after chemotherapy. In both cases, monoclonal integration of HTLV-I provirus was demonstrated in the genomic DNA from each bone lesion. Although their clinical courses and pathological findings were different, ATL in both patients began as a bone lesion, showing that primary lymphoma of bone can be manifested in ATL cases.
Asunto(s)
Neoplasias Óseas/virología , Huesos/virología , ADN Viral/genética , Leucemia de Células T/virología , Provirus/aislamiento & purificación , Integración Viral , Adulto , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/patología , Huesos/diagnóstico por imagen , Huesos/patología , Femenino , Infecciones por HTLV-I/diagnóstico por imagen , Infecciones por HTLV-I/patología , Infecciones por HTLV-I/virología , Humanos , Leucemia de Células T/diagnóstico por imagen , Leucemia de Células T/patología , Masculino , Osteólisis/diagnóstico por imagen , Osteólisis/etiología , Osteólisis/patología , Reacción en Cadena de la Polimerasa , Provirus/genética , RadiografíaRESUMEN
Anti-Tac monoclonal antibody recognizes human interleukin-2 receptor, which is overexpressed in leukemic cells of most adult T-cell leukemia (ATL) patients. To examine the potency of anti-Tac for targeting of ATL, biodistributions of intravenously administered 125I- and 111In-labeled anti-Tac were examined in severe combined immunodeficiency (SCID) mice inoculated with ATL cells. Significant amounts of radiolabeled anti-Tac were found in the spleen and thymus. The trafficking of ATL cells in SCID mice was detected using 111In-oxine-labeled ATL cells. These results were coincident with the histologically confirmed infiltration of ATL cells. The radiolabeled anti-Tac seemed potent for targeting of ATL.
Asunto(s)
Inmunoconjugados , Radioisótopos de Indio , Radioisótopos de Yodo , Leucemia de Células T/diagnóstico por imagen , Radioinmunodetección , Adulto , Animales , Anticuerpos Monoclonales/farmacocinética , Humanos , Inmunoconjugados/metabolismo , Inmunoconjugados/farmacocinética , Leucemia de Células T/metabolismo , Ratones , Ratones SCID , Compuestos Organometálicos/metabolismo , Oxiquinolina/análogos & derivados , Oxiquinolina/metabolismo , Receptores de Interleucina-2/inmunología , Distribución TisularRESUMEN
131I-labelled anti-thymoglobuline (ATG), 131I-labelled immunoconjugate ATG-Dex-DNR and 131I-labelled Ts-MoAb as control antibody, respectively, were injected by intraperitoneal (i.p.) administration into nude mice used as models for human T-cell leukemia. SPECT imaging was performed from day 1 to day 8 following i.p. injection. The results showed that radioimmunoimaging of human tumor xenografts was clearest day 3 after injection in both of ATG and ATG-Dex-DNR groups, whereas it's not the case in Ts-MoAb group. Nude mice were killed 8th day after injection with antibody or conjugate. The tumor, as well as different dissected normal organs including heart, liver, lungs, kidney, femur and intestine, were harvested, weighed precisely, and radioiodine-counted. T/NT ratios in experimental group was greater than 1.0 (ranged from 1.246-7.865), and in control group they were less than 1.0 (ranged from 0.263-0.757, except for tumor/femur ratio). Our results indicated that ATG and ATG-Dex-DNR had specific affinity to cell line of T-cell leukemia CEM.
Asunto(s)
Daunorrubicina/farmacocinética , Inmunotoxinas/farmacocinética , Leucemia de Células T/metabolismo , Radioinmunodetección , Animales , Anticuerpos Monoclonales , Inmunoglobulinas/inmunología , Leucemia de Células T/diagnóstico por imagen , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Antígenos Thy-1/inmunología , Distribución Tisular , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
A 49-year-old woman was admitted to the hospital with supraclavicular lymph node swelling. On a chest x-ray film, a 4 x 4-cm nodular shadow was observed in the right middle lung field. The white blood cell count was 10,100/cu mm, showing 44 percent abnormal lymphocytes with lobulated nuclei. Since HTLV-I antibodies were markedly positive, she was diagnosed as having ATL. Transbronchial tumor biopsy revealed accumulation of ATL cells. Our patient is the first case with only a large nodular accumulation of ATL cells without diffuse infiltration of the cells in the lung.
Asunto(s)
Leucemia de Células T/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Femenino , Humanos , Leucemia de Células T/patología , Neoplasias Pulmonares/patología , Persona de Mediana Edad , RadiografíaRESUMEN
Although Ga-67 has been used extensively in imaging many different conditions, much is yet unknown about the mechanisms by which gallium concentrates preferentially in tissues such as the liver. This paper reports three patients with markedly diminished hepatic uptake of gallium. The cases are examined in light of published data demonstrating such factors as transferrin levels, radiation, and chemotherapeutic agents as altering the hepatic uptake of gallium. Of the many factors believed to influence the biodistribution of gallium, none can definitively account for the lack of hepatic uptake in these patients.