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Os tumores uretrais são patologias extremamente raras, representando menos de 1% de todas as neoplasias e menos de 0,1% das neoplasias genitourinárias. Até à data, estão descritos em humanos apenas cerca de 600 casos, quer do sexo masculino como feminino. A uretra, o tracto geniturinário e também a bexiga derivam embriologicamente de uma mesma estrutura, no entanto, os tumores que surgem nestes diferentes locais são distintos. O tumor mais frequentemente observado a nível uretral é o carcinoma das células escamosas, seguido pelo carcinoma das células de transição. A infecção e a irritação crónica são apontadas como factores etiológicos na carcinogénese da neoplasia uretral. No presente estudo, administrámos na água de bebida, N-butil-N-(4-hidroxibutil) nitrosamina (BBN) a um grupo de murganhos ICR, durante 12 semanas. Um outro grupo foi utilizado como controlo negativo. Os animais foram eutanasiados em três períodos diferentes e a bexiga e a uretra foram colhidas para procedimento histopatológico. Com este estudo, pretendemos mostrar as alterações pré-neoplásicas e neoplásicas induzidas pela BBN na uretra destes animais. De acordo com a bibliografia consultada, este é, até à data, o primeiro relato do efeito directo da BBN no epitélio uretral.

Purpose: Molecular imaging and targeted radiotherapy are emerging fields in nuclear oncology. Five human somatostatin receptors (hsstr1-hsstr5) are known to be overexpressed to some degree on various tumors, sstr2 being the most important one. Clinically used somatostatin based radiopeptides target exclusively sstr2. The aim of this study was to develop novel analogues with a broader sstr profile for diagnostic (positron emission tomography and single-photon emission computed tomography) and radiotherapeutic applications. Experimental Design: The following promising structures emerged from a parallel synthetic approach: [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA0),1-Nal3,Thr8]-octreotide (1, DOTA-NOC-ATE) and [DOTA0,BzThi3,Thr8]-octreotide (2, DOTA-BOC-ATE). The conjugates were labeled with cold and radioactive 111In. Pharmacologic properties were compared with [111In-DOTA,Tyr3]-octreotide ([111In-DOTA]-TOC). Results: The receptor affinity profile showed high affinity of both peptides to hsstr2, hsstr3, and hsstr5 and some intermediate affinity to hsstr4, whereas [111In-DOTA]-TOC shows affinity only to sstr2. The internalization is fast in sstr2 expressing AR4-2J and in transfected sstr3 expressing human embryonic kidney 293 cells. Both radiopeptides internalize much more efficiently than [111In-DOTA]-TOC. Animal biodistribution studies showed very high and specific uptake of [111In]-1 and [111In]-2 in s.c. implanted AR4-2J tumors (Lewis rats) and in somatostatin receptor expressing normal tissues. The uptake was at least 2-fold higher in these tissues and in the tumor compared with [111In-DOTA]-TOC. In addition, the kidney uptake was significantly lower for both radiopeptides. Conclusions: These data suggest that the novel radiopeptides are superior to [111In/90Y-DOTA]-TOC and show great promise for the clinical application in the imaging of somatostatin receptor–positive tumors and their targeted radiotherapy.