RESUMEN
Annexin A5 (AnxA5) is a protein with high affinity for phosphatidyl serine, a phospholipid exposed on the cell surface during apoptosis. This phenomenon has been used for determination of cell death after myocardial infarction. To evaluate the potential of (99m)Tc-AnxA5 for in vivo scintigraphy of apoptotic cells, the pharmacokinetics and imaging properties of two radiopharmaceuticals, (99m)Tc-(n-1-imino-4-mercaptobutyl)-AnxA5 (I-AnxA5) and (99m)Tc-(4,5-bis(thioacetamido)pentanoyl)-AnxA5 (B-AnxA5), were studied. I-AnxA5 was administered intravenously to seven patients and one healthy volunteer, and B-AnxA5 was administered to 12 patients. All patients in the pharmacokinetic study had myocardial disease. Additionally, imaging was performed in a patient with acute myocardial infarction, as well as in three patients with different malignancies. The plasma concentration, excretion and biodistribution of (99m)Tc-AnxA5 were measured, as well as levels of AnxA5 antigen. The kinetic data of both radiopharmaceuticals in plasma fitted a two-compartment model. Both preparations had similar half-lives, but a different distribution over the two compartments. Plasma levels of AnxA5 antigen showed a broad variation. Both radiopharmaceuticals accumulated in the kidney, liver and gut. B-AnxA5 was excreted significantly faster than I-AnxA5. Both compounds can be used for imaging of the head/neck region, the thorax and the extremities. B-AnxA5 has a faster clearance and a lower radiation dose. Imaging of apoptosis in the abdomen will be difficult with both radiopharmaceuticals, and especially with B-AnxA5 because of its faster appearance in the gut.
Asunto(s)
Anexina A5/farmacocinética , Cardiomiopatías/diagnóstico por imagen , Compuestos de Organotecnecio/farmacocinética , Radiofármacos/farmacocinética , Adulto , Anciano , Anciano de 80 o más Años , Anexina A5/sangre , Apoptosis , Disponibilidad Biológica , Neoplasias de la Mama/diagnóstico por imagen , Semivida , Humanos , Linfoma no Hodgkin/diagnóstico por imagen , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Compuestos de Organotecnecio/sangre , Radiofármacos/sangre , Sarcoma/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
Programmed cell death plays a critical role in embryology, homeostasis and disease. However, until recently no non-invasive imaging modality has been able to visualize this process directly. Annexin A5 binds to cells undergoing programmed cell death. When labeling this protein, Annexin A5 becomes a tool for the detection of programmed cell death in vitro and in vivo. Labeled Annexin A5 has enabled our group and others to detect programmed cell death non-invasively in animals and patients. This review will highlight the development of this imaging modality in cellular and animal models. Furthermore, we will discuss Annexin A5 imaging in human disease. We will focus on the clinical applications and their relevance, limitations and future perspectives of non-invasive imaging of programmed cell death using labeled Annexin A5.
Asunto(s)
Anexina A5/farmacocinética , Apoptosis , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Radiofármacos/farmacocinética , Animales , Humanos , Ratones , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/metabolismo , Compuestos de Organotecnecio/farmacocinética , CintigrafíaRESUMEN
BACKGROUND: Primary endocardial tumours are rare, but may impose a difficult clinical problem. The definite diagnosis regarding the nature of the tumour is often made after surgery. This is due to the fact that current non-invasive imaging techniques are unable to inform us about the nature of the tumour. In addition, invasive techniques can not be used to obtain biological information of the tumour in these cases, because they carry a high risk of embolic complications. OBJECTIVE: To assess the possibility of a novel modality of imaging, molecular imaging, in the diagnosis of primary intracardiac tumours. METHODS: We evaluated two patients with a primary cardiac tumour. Prior to therapy, we infused human recombinant annexin-V Tc99-m and thallium 201. We used a dual isotope single photon emission computed tomography technique. This allowed us to obtain information about the relation between the anatomical position of the left ventricle and the uptake of the labelled annexin-V within the thoracic cavity. RESULTS: The patient with a malignant primary cardiac tumour showed uptake of labelled annexin-V within the area of the tumour. After surgery, the malignant nature was confirmed by histological analysis. The patient with a benignant intracardiac tumour showed no uptake of annexin-V within the area of the tumour. CONCLUSION: This novel imaging technique, molecular imaging, may be of help to differentiate non-invasively between a malignant and benignant primary intracardiac tumour.