INTRODUCTION Alzheimer disease is related to several risk factors including aging, family history, high blood pressure and diabetes. Studies have shown specific regional cerebral perfusion changes in patients with Alzheimer disease. Some authors state that these changes could appear years before patient memory becomes impaired, enabling early diagnosis in high-risk persons who appear to be healthy.

OBJECTIVE Determine the usefulness of cerebral perfusion studies in Alzheimer patients and first-degree relatives for obtaining additional diagnostic information and detecting functional changes that may suggest elevated disease risk.

METHODS This study involved 128 persons (87 clinically diagnosed with Alzheimer disease and 41 of their first-degree relatives with normal cognition), all from Artemisa Province, Cuba. We performed clinical, laboratory, neuropsychological and genetic (apolipoprotein E—ApoE, e4 allele) tests, as well as cerebral perfusion studies using single photon emission computed tomography after administering 740–925 MBq of 99m Tc-ECD, following internationally standardized protocols.

RESULTS In the Alzheimer disease group, the cerebral single photon emission computed tomography showed a typical Alzheimer pattern (bilateral posterior temporal-parietal hypoperfusion) in 77% (67/87) of participants; 35.9% (28/67) in stage 1; 51.3% (40/67) in stage 2; and 12.8% (10/67) in stage 3 of the disease. In this group, 12.7% (11/87) had mild or unilateral cerebral perfusion changes; 5.7% (5/87) vascular dementia; 3.4% (3/87) frontal dementia; and 1.2% (1/87) normal cerebral perfusion. Of the patients, 28.7% (25/87) received a different classification of stage and disease diagnosis after cerebral perfusion results were considered. In the relative group, 14.6% (6/41) had cerebral perfusion abnormalities. Among these, 7.1% (3/41) were mild bilateral temporal–parietal hypoperfusion; 4.8% (2/41) mild unilateral temporal–parietal hypoperfusion; and 2.4% (1/41) had perfusion defecits in their right frontal lobes. Of patients with typical Alzheimer disease patterns in the cerebral single photon emission computed tomography, 76.6% (52/67) had positive ApoE e4. All relatives with perfusion abnormalities (6/6) had positive ApoE e4.

CONCLUSIONS Cerebral perfusion studies confirmed the Alzheimer disease diagnosis, classified disease stages, and differentiated between the types of dementia. The test showed perfusion changes in several asymptomatic first-degree relatives with positive ApoE e4, which could be predictors of disease. The technique was useful for evaluating patients and their relatives.

KEYWORDS Cerebrovascular circulation; tomography, emission-computed, single-photon; Alzheimer disease; Alzheimer’s disease; Cuba

INTRODUCCIÓN La disponibilidad de los anticuerpos monoclonales en Cuba facilitó el desarrollo y la aplicación de técnicas innovadoras (inmunogammagrafía y radioinmunoterapia) para el diagnóstico y el tratamiento del cáncer.

OBJETIVO Revisar la literatura sobre las técnicas de inmunogammagrafía y radioinmunoterapia, y analizar su uso en Cuba. Se describe la experiencia del Centro de Investigaciones Clínicas de La Habana con anticuerpos monoclonales marcados para el diagnóstico y el tratamiento del cáncer durante el período 1993–2013.

RECOPILACIÓN DE LAS EVIDENCIAS Se revisaron los conceptos básicos sobre cáncer y anticuerpos monoclonales, así como los resultados relevantes internacionales y cubanos. Se estudiaron 49 documentos: 2 libros de texto, 34 artículos de autores cubanos y 13 de autores internacionales. Se incluyeron todos los trabajos publicados por el Centro de Investigaciones Clínicas desde 1993 hasta 2013. La bibliografía se obtuvo de la biblioteca del Centro de Investigaciones Clínicas y de Infomed, la red telemática nacional de salud de Cuba, y se utilizaron las siguientes palabras clave: anticuerpos monoclonales, inmunogammagrafía y radioinmunoterapia (en inglés y en español).

RESULTADOS El marcaje de los anticuerpos (ior t3, ior t1, ior cea1, ior egf/r3, ior c5, h-R3, 14 F7 y rituximab) con los isótopos radiactivos constituyó una línea básica de investigación en Cuba y permitió su uso para el diagnóstico y la terapéutica. Los estudios realizados demuestran la buena sensibilidad y la precisión diagnóstica de la inmunogammagrafía para la detección de varios tipos de tumores (cabeza y cuello, ovario, colon, mama, cerebro, y linfoma).

La obtención de conjugados radioinmunes con isótopos radiactivos como el 99mTc y el 188Re permitió el radioinmunodiagnóstico y la administración de la radioinmunoterapia a los pacientes con varios tipos de cánceres (cerebro, mama, linfomas). El 60% de los ensayos clínicos se propuso determinar la farmacocinética, la dosimetría interna y los efectos adversos de los anticuerpos monoclonales, así como la respuesta tumoral; hubo pocos efectos adversos, no se observó daño en los órganos vitales, y hubo una respuesta antitumoral en una proporción sustancial de los pacientes.

CONCLUSIONES Cuba tiene experiencia en la producción y el radiomarcaje de los anticuerpos monoclonales, lo que facilita el uso de estos agentes. Los estudios realizados por el Centro de Investigaciones Clínicas durante los pasados 20 años muestran resultados satisfactorios. La evidencia obtenida sugiere un prometedor potencial de los anticuerpos monoclonales y de la medicina nuclear, ya que las técnicas de radioinmunodiagnóstico y radioinmunoterapia proporcionan alternativas para el diagnóstico y el tratamiento del cáncer en Cuba.

PALABRAS CLAVE Inmunogammagrafía, radioinmunoterapia, conjugado radioinmune, marcaje, anticuerpo monoclonal, inmunocromatografía, radioinmunodetección, radiomarcaje, Cuba

INTRODUCTION The availability of monoclonal antibodies in Cuba has facilitated development and application of innovative techniques (immunoscintigraphy and radioimmunotherapy) for cancer diagnosis and treatment.

Objective Review immunoscintigraphy and radioimmunotherapy techniques and analyze their use in Cuba, based on the published literature. In this context, we describe the experience of Havana’s Clinical Research Center with labeled monoclonal antibodies for cancer diagnosis and treatment during the period 1993–2013.

EVIDENCE ACQUISITION Basic concepts concerning cancer and monoclonal antibodies were reviewed, as well as relevant international and Cuban data. Forty-nine documents were reviewed, among them 2 textbooks, 34 articles by Cuban authors and 13 by international authors. All works published by the Clinical Research Center from 1993 through 2013 were included. Bibliography was obtained from the library of the Clinical Research Center and Infomed, Cuba’s national health telematics network, using the following keywords: monoclonal antibodies, immunoscintigraphy and radioimmunotherapy.

RESULTS Labeling the antibodies (ior t3, ior t1, ior cea 1, ior egf/r3, ior c5, h-R3, 14F7 and rituximab) with radioactive isotopes was a basic line of research in Cuba and has fostered their use as diagnostic and therapeutic tools. The studies conducted demonstrated the good sensitivity and diagnostic precision of immunoscintigraphy for detecting various types of tumors (head and neck, ovarian, colon, breast, lymphoma, brain).

Obtaining different radioimmune conjugates with radioactive isotopes such as 99mTc and 188Re made it possible to administer radioimmunotherapy to patients with several types of cancer (brain, lymphoma, breast). The objective of 60% of the clinical trials was to determine pharmacokinetics, internal dosimetry and adverse effects of monoclonal antibodies, as well as tumor response; there were few adverse effects, no damage to vital organs, and a positive tumor response in a substantial percentage of patients.

CONCLUSIONS Cuba has experience with production and radiolabeling of monoclonal antibodies, which facilitates use of these agents. Studies in Cuba conducted by the Clinical Research Center over the past 20 years have yielded satisfactory results. Evidence obtained suggests promising potential of monoclonal antibodies and nuclear medicine, with immunoscintigraphy and radioimmunotherapy techniques providing alternatives for cancer diagnosis and treatment in Cuba.

KEYWORDS Immunoscintigraphy, radioimmunotherapy, radioimmune conjugate, labeling, monoclonal antibody, immunochromatography, radioimmunodetection, radiolabeled immunoscintigraphy, Cuba

INTRODUCTION Silent myocardial ischemia is frequent in type 2 diabetics, therefore, symptoms cannot be relied upon for diagnosis and followup in these patients. Various studies relate blood lipid levels to cardiovascular diseases, and several authors describe certain lipoproteins as independent predictors of ischemia.

OBJECTIVE Identify blood lipid levels that predict silent myocardial ischemia in a type 2 diabetic population in Havana.

METHODS From May 2005 through May 2009, assessment was done of 220 asymptomatic type 2 diabetics in ten polyclinics in Havana using laboratory tests and Single-Photon Emission-Computed Tomography, synchronized with electrocardiogram, known as gated SPECT (gSPECT). Coronary angiography was used for confirmation when gSPECT detected ischemia. Patients were classified into two groups: gSPECT positive and gSPECT negative. Descriptive statistics (mean and standard deviation) were calculated for all variables and mean comparison tests were conducted. Classification trees were developed relating lipid values to gSPECT results, identifying optimal cutoff points for their use as indicators of silent myocardial ischemia in the total study population and for each sex separately.

RESULTS GSPECT found silent myocardial ischemia in 29.1% of those examined, and 68.4% of angiograms found multivessel disease. gSPECT-positive diabetics had higher levels of total cholesterol, LDL, and triglycerides (p < 0.05). HDL levels were lower in this group (p < 0.05). Classification trees showed optimal cutoff points, indicators for silent ischemia, for: HDL ≤44 mg/dL, LDL >119.9 mg/dL, and triglycerides >107.2 mg/d; 80.4% of diabetics with these HDL and triglyceride values had ischemia. HDL was the most important normalized variable when the entire population was analyzed. Analysis by sex showed a greater percentage of silent ischemia in men (33.3%) than in women (24.8%). The most important normalized variables were LDL of >100.8 mg/dL for men and HDL of ≤44 mg/dL for women.

CONCLUSIONS A considerable percentage of the study population had silent myocardial ischemia. Type 2 diabetics with ischemia had higher levels of total cholesterol, LDL and triglycerides. HDL levels were significantly lower in these patients. The association of low HDL with high triglycerides was a strong indicator of myocardial ischemia in type 2 diabetics without clinical cardiovascular signs.

KEYWORDS Lipids, type 2 diabetes, silent myocardial ischemia, decision trees, diagnostic imaging, Single-Photon Emission-Computed Tomography, cardiac-gated SPECT, early detection, Cuba