Abstract

BACKGROUND:

Emerging imaging technologies such as real-time multispectral imaging (rMSI) hold great potential for simultaneous visualization of multiple target structures using fluorophores on various tumours including bladder cancer (BC). These technologies, however, require a multi-step preclinical evaluation process, including mouse models.

OBJECTIVE:

To demonstrate the suitability of the new rMSI technology for the detection of premalignant lesions and malignant BC in a preclinical mouse model using contrast agents.

METHODS:

Tumours were induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), which is known to induce BC in rodent models. In total, 30 mice (C57BL/6) were fed with 0.1% BBN ad libitum in drinking water for up to 5 months. Bladders were excised at 3 (n = 6) and 5 months (n = 24) of treatment and incubated ex vivo with Hexaminolevulinat (HAL, Hexvix®), CD47-FITC, CD90.2-FITC or a combination of CD90.2-FITC/CD47-FITC and HAL. The bladders were analyzed by an endoscopic rMSI prototype system equipped with a spectral filter (Chroma), a 4 mm endoscope (Karl Storz) with 30° optic, a LED light source and a PC with a microcontroller board.

RESULTS:

5-month treatment of mice with 0.1% BBN led to the formation of squamous carcinoma (46%, n = 11) while urothelial carcinoma was observed only in one mouse (4%, n = 1). Carcinoma in situ (CIS) was detectable in twelve out of twenty-four mice (50%, n = 12) treated for 5 month and in three out of six mice (50%, n = 3) treated for 3 months.The metabolite of HAL, protoporphyrin IX (PpIX), could be reliably and specifically detected in all of mouse bladder tumours and CIS. However, detection of the CD90.2 surface marker was less reliable, potentially due to species- or tumour-subtype specificity.

CONCLUSIONS:

This model offers the potential for preclinical imaging studies with combined fluorescence targets, e.g. HAL, in combination with BC-specific antibodies.

中文翻译：

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使用临床前体内模型检测膀胱癌的实时多光谱成像技术的建立

摘要

背景：

诸如实时多光谱成像（rMSI）之类的新兴成像技术具有巨大的潜力，可以使用荧光团在包括膀胱癌（BC）在内的各种肿瘤上同时可视化多个目标结构。但是，这些技术需要多步骤的临床前评估过程，包括鼠标模型。

目的：

为了证明新的rMSI技术适用于使用造影剂在临床前小鼠模型中检测癌前病变和BC恶性的适用性。

方法：

N-丁基-N-（4-羟丁基）-亚硝胺（BBN）诱导了肿瘤，已知它会在啮齿动物模型中诱导BC。总共给30只小鼠（C57BL / 6）喂食了0.1％BBN的饮用水，长达5个月。囊物在切下3（Ñ  = 6）和5个月（Ñ 治疗= 24），并温育体外与Hexaminolevulinat（HAL，Hexvix®），CD47-FITC，CD90.2-FITC或CD90.2-的组合FITC / CD47-FITC和HAL。膀胱通过内窥镜rMSI原型系统进行分析，该原型系统配备有光谱滤光片（Chroma），带30°光学元件的4毫米内窥镜（Karl Storz），LED光源和带有微控制器板的PC。

结果：

用0.1％BBN的小鼠进行5个月的治疗会导致鳞状癌的形成（46％，n  = 11），而仅在一只小鼠中观察到了尿路上皮癌（4％，n  = 1）。癌原位（CIS）中12为可检测出24只小鼠（50％，的Ñ 为5个月处理= 12）和在三个出六只小鼠（50％，的Ñ  3个月。代谢物治疗= 3） HAL中的原卟啉IX（PpIX）可以在所有小鼠膀胱肿瘤和CIS中可靠且特异性地检测到。但是，检测CD90.2表面标记的可靠性较差，这可能是由于物种或肿瘤亚型的特异性所致。

结论：

该模型为结合联合的荧光靶标（例如HAL）和BC特异性抗体的临床前成像研究提供了潜力。