Bone marrow bi-hypoplasia in a dog with a sertoli cell tumor / Hipoplasia dupla de medula óssea em um cão com tumor de células de sertoli

A 20-year-old unneutered male poodle presented prostration, apathy, staggering gait, lack of appetite and tick infestation. The dog was diagnosed with a Sertoli cell tumor in an undescended testicle by cytological, histopathological and immunohistochemical tests. Pancytopenia with moderate nonregenerative anemia, leukopenia and severe thrombocytopenia were detected in the complete blood count. Cytological and histopathological evaluation of the bone marrow revealed a cellularity of 30%, with erythroid (59%), lymphoid (40%) and mast cells (1%), and an absence of granulocytic, monocytic and megakaryocytic lineage cells. In post-mortem examinations, changes related to hemostatic disorders were found. The absence of microorganisms in molecular tests and an estrogen serum concentration over reference values confirmed hyperestrogenism as a possible cause of pancytopenia. The literature describes a Sertoli cell tumor hyperestrogenism that induced pancytopenia, along with bone marrow hypoplasia of all hematopoietic lineages. In contrast, in the present case, the erythroid precursor cells were preserved in the bone marrow, although there were no reticulocytes circulating in the blood. This case, therefore, should be considered in future investigations of pancytopenia induced by Sertoli cell tumor hyperestrogenism.(AU)

Um cão Poodle, macho, de 20 anos, não castrado, apresentou prostração, apatia, andar cambaleante, falta de apetite e infestação por carrapatos. Nesse animal, foi diagnosticado tumor de células de Sertoli em um testículo não descendente, utilizando-se citologia, histopatologia e imuno-histoquímica. Pancitopenia com anemia moderada não regenerativa, leucopenia e trombocitopenia intensas foram detectadas no hemograma. Na avaliação citológica e histopatológica da medula óssea, havia celularidade de 30%, constituída pelas linhagens eritroide (59%) e linfoide (40%) e por mastócitos (1%), com ausência de células das linhagens granulocítica, monocítica e megacariocítica. Em exames post mortem, mudanças relacionadas à hemostasia foram encontradas. A ausência de micro-organismos nos testes moleculares e a concentração sérica de estrogênio acima dos valores de referência confirmaram hiperestrogenismo como a possível causa da pancitopenia. A literatura descreve hiperestrogenismo em tumores de células de Sertoli induzindo pancitopenia associada com hipoplasia da medula óssea de todas as linhagens hematopoiéticas. Em contraste, no presente caso, as células precursoras eritróides estavam preservadas na medula óssea, embora não houvesse reticulócitos no sangue. Assim, o relato apresentado deve ser considerado em futuras investigações de pancitopenia induzida por hiperestrogenismo em tumor de células de Sertoli.(AU)

Novel series of (177)Lu-labeled bombesin derivatives with amino acidic spacers for selective targeting of human PC-3 prostate tumor cells.

AIM: Bombesin (BBN) has demonstrated the ability to bind with high affinity and specificity to GRP receptor, overexpressed on human prostate cancer. A large number of BBN derivatives have been synthesized for this purpose but most of them exhibit high abdominal accumulation, which may represent a problem in their clinical use due to serious side effects to patients. In this study we describe the results of radiolabeling with lutetium-177, stability and in vivo studies of novel phenyl-glycine-extended bombesin derivatives. The spacers were inserted to improve bombesin in vivo properties and to reduce its target to non-tumor sites. METHODS: Preliminary studies were done to establish the ideal conditions for labeling bombesin derivatives. Chromatography systems were applied to determine free lutetium and the stability of the preparations was evaluated either after storing at 2-8 ºC or incubation in human serum at 37 ºC. In vivo experiments included biodistribution, pharmacokinetics and SPECT images and were performed in Balb-c and Nude mice bearing PC-3 xenografts. RESULTS: The derivatives were labeled with high yield and kept stable at 2-8 ºC and are metabolized by human serum enzymes. In vivo studies showed fast blood clearance of labeled peptides and rapid excretion, performed mainly by renal pathway. In addition, biodistribution and imaging studies showed low abdominal accumulation and significant and specific tumor uptake of (177)Lu-labeled derivatives. CONCLUSIONS: The derivative with longer spacer holds a higher potential as radiopharmaceutical for prostate tumor diagnosis and the derivatives with shorter spacers are potential radiopharmaceuticals for prostate tumor treatment.

In vivo comparative study of hydroxyapatite labeled with different radioisotopes: evaluation of the scintigraphic images.

Radyosinovectomy (RSV) is a radiotherapeutic modality where a beta-emitting radionuclide is administered locally by intra-articular injection on the form of a colloid or radiolabeled particulate. RSV is a well-accepted therapeutic procedure in inflammatory joint diseases and has been successfully employed for more than 50 years as a viable alternative to surgical and chemical synovectomy. The aim of this work is to compare the in vivo stability of hydroxyapatite labelled with (177)Lu, (90)Y and (153)Sm. All radionuclides were labelled with high yield and were retained in the joint for 7 days, showing stability and usefulness as tools in the RSV treatment. A similar retention of the products in the muscle was observed when the particles were administrated in the muscle. However, the pure form of the radionuclides were rapidly cleared from the blood and accumulated in the liver when injected i.v.. Although (153)Sm-HA is already available for nuclear medicine procedures and clinical studies with (90)Y-HA have been developed, (177)Lu-labeled RSV agents will be economically more viable and has not been studied yet. Its favorable characteristics contribute to follow, to predict and asses the success of RSV by bone scintigraphy studies.

A comparative study of 131I and 177Lu labeled somatostatin analogues for therapy of neuroendocrine tumours.

This work analysed the influence of the chelating group and radioligand on somatostatin analogues in vivo and in vitro properties. The presence of DOTA in the radioiodinated peptide produced a labeled analogue with similar blood kinetics and biodistribution to (177)Lu-DOTATATE and with lower abdominal uptake than (131)I-TATE. In addition, (131)I-DOTATATE showed significative tumour uptake, despite not so persistent after 24h. (131)I-DOTATATE can represent a cost-effective alternative to lutetium labeled peptide for neuroendocrine tumours therapy.