Mariani G, Collecchi P, Baldassarri S, Di Luca L, Buralli S, Fontanini G, Baranowska-Kortylewicz J, Adelstein S J, Kassis A I
CNR Institute of Clinical Physiology, University of Pisa, Italy.
J Nucl Med. 1996 Apr;37(4 Suppl):16S-19S.
In patients with bladder cancer, little is known about diffusion in the tumor mass of 5-iodo-2'-deoxyuridine (IUdR) administered intraluminally, although previous studies based on external scanning have shown promising tumor-targeting properties of IUdR instilled intravesically. This study compared the pattern of IUdR uptake by bladder cancer cells with the actual distribution of mitotic activity, as evaluated by incubation of ex vivo tumor specimens with tritiated thymidine.
The [125I]IUdR (2-13 MBq) was instilled over 1-3 hr in the bladder of four patients with bladder cancer scheduled for ablative surgery. Twenty-four hours later, surgical samples were assayed for radioactivity and processed for microautoradiography, while fresh tumor specimens were fragmented, incubated with [3H]thymidine and further processed for microautoradiography. The diffusion of labeled IUdR across the bladder wall was evaluated by blood sampling.
Tumor incorporation of [125I]IUdR 24 hr after intravesical instillation was 0.002%-0.05% ID/g, while the average tumor-to-normal bladder ratio was about 20. Microautoradiography showed that [125I]IUdR incorporation was confined to tumor cells in the most superficial layers of the bladder, while incubation of the tumor fragments with [3H]thymidine demonstrated the presence of diffuse mitotic activity also in the deeper tumor mass. Diffusion of labeled IUdR in the general circulation was minimal.
Poor diffusion in the tumor mass makes *IUdR unsuitable for intracavitary therapy of bladder cancer, but the role of such an approach in the postsurgical "sterilization" of cancer remnants floating in the bladder lumen after partial cystectomy should be explored.
在膀胱癌患者中,对于腔内注射5-碘-2'-脱氧尿苷(IUdR)后在肿瘤块中的扩散情况了解甚少,尽管先前基于外部扫描的研究表明膀胱内灌注的IUdR具有良好的肿瘤靶向特性。本研究通过用氚标记的胸腺嘧啶核苷孵育离体肿瘤标本评估有丝分裂活性的实际分布,比较了膀胱癌细胞摄取IUdR的模式。
将[125I]IUdR(2 - 13 MBq)在1 - 3小时内灌注到4例计划进行切除手术的膀胱癌患者的膀胱中。24小时后,对手术样本进行放射性测定并进行显微放射自显影处理,同时将新鲜肿瘤标本切碎,与[3H]胸腺嘧啶核苷一起孵育,然后进一步进行显微放射自显影处理。通过采血评估标记的IUdR在膀胱壁中的扩散情况。
膀胱内灌注后24小时,肿瘤对[125I]IUdR的摄取量为0.002% - 0.05% ID/g,而肿瘤与正常膀胱的平均比值约为20。显微放射自显影显示,[125I]IUdR的摄取局限于膀胱最表层的肿瘤细胞,而用[3H]胸腺嘧啶核苷孵育肿瘤碎片表明,在更深层的肿瘤块中也存在弥漫性有丝分裂活性。标记的IUdR在体循环中的扩散极小。
IUdR在肿瘤块中的扩散不佳,使其不适用于膀胱癌的腔内治疗,但应探索这种方法在部分膀胱切除术后漂浮在膀胱腔内的癌残留“消毒”中的作用。