CN100382846C - 用于改进成像及光动力治疗的方法 - Google Patents
用于改进成像及光动力治疗的方法 Download PDFInfo
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- CN100382846C CN100382846C CNB998129917A CN99812991A CN100382846C CN 100382846 C CN100382846 C CN 100382846C CN B998129917 A CNB998129917 A CN B998129917A CN 99812991 A CN99812991 A CN 99812991A CN 100382846 C CN100382846 C CN 100382846C
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Abstract
本发明指的是一部仪器,及至少用一种光动力治疗(“PDT”)剂进行成像与治疗的方法。该方法包括给患者956)服用一种光激活药剂,用一部成像设备(52)如CAT扫描或MRI为患者成像以对患者体内的患病组织或肿瘤(54)进行定位,并且足以光激光该组织内的该药剂的光(60)来治疗已成像的患病组织。
Description
技术领域
本项发明涉及一部诊疗仪和至少使用一种光动力医疗(photodynamictherapy,“PDT”)剂来成像和治疗的方法。细言之,该诊疗仪及方法用于对患病的组织进行成像和治疗。
背景技术
成像一般用于对体内的患病组织或肿瘤进行定位。患病组织的位置一经确定,随之将以某种方式对其进行治疗,以便杀灭该组织内患病的细胞。正如下面所述,以往,这是两个独立的疗程,时间拉得过长,而且常常是不成功的。
通常,成像是用成像设备如CAT(计算机轴向层析X光摄影)扫描机或MRI(磁共振成像)设备来实现的。此外,还可以使用X光间接摄影法(用由X射线在荧光屏上生成的图像)或者类似的过程。这些成像过程中的每一过程均要求一种造影剂(contrast agent),以获得最佳性能。这种成像造影剂的例子包括用于x射线成像的碘化剂例如欧乃哌克TM(碘海醇)和OmniscanTM(加多米特)或多种顺磁MRI造影剂如DPTA钆(Gd-DPTA)中的一种。
患病组织的位置一经成像的方式得到确定,即需对其加以治疗。然而,这种治疗常常是不成功的。
目前对癌症的全部疗法(例如放射线疗法及化学疗法)均是以对迅速增生的细胞施以攻击的方式进行的。不幸的是,这种目标选定的依据并不仅限于对癌细胞的治疗效果。结果,这些疗法伴有不希望出现的会威及生命的副作用。而且,这样的疗法实际上会削弱人体固有的对肿瘤的防御能力。例如,放疗及化疗就会对迅速分裂的免疫细胞造成伤害,使抗肿瘤及抗干染的反应受到抑制。
除了产生不希望出现的副作用之外,目前的疗法大多不能达到预期的疗效,因其并非专门对癌细胞进行攻击。因此,放疗或化疗的单独或联合使用均难以治愈癌症。因而,目前对癌的首要疗法是手术切除肿瘤。这通常还要与辅助的放疗及化疗相配合。因此,为了治愈,患者要遭受手术之苦,并在着力杀灭全部癌细胞的过程中遭受高毒疗法的毒害。
为尽量缩小癌症治疗造成的侵害并提高综合疗效,光动力疗法(PDT)被开发出来。光动力疗法是光敏剂与特定部位照视法的结合,以便在确定的组织,比如一个肿瘤中,产生对治疗的反应。光敏剂吸收光子后达到激活状态,继而有效。不幸的是,在PDT中照视这一步骤所使用的常规的单光子激活(SPE)方法无法使PDT发挥其潜力,主要因为(1)该疗法所要求的高能光无法深入到组织内部,并且(2)该照视法只允许医生对治疗部位进行最小的空间控制。与此相反,双光子激活(TPE)PDT所使用的低能光能够安全地穿透组织并对治疗的界限提供三维控制。
在共同拥有的美国专利U.S.S.N.08/739,801中提供了对TPE及SPE的更为详细的解释,这里引用以作为参考。
在PDT中使用双光子激活明显地改进了穿透深度和困扰着常规PDT的空间控制问题,同时,由于PDT剂医疗性能的改进以及在选择激活部位方面确定病变特异性的改进,可以获得其它的改进。这是由于当前使用的PDT剂以及激活所选目标的手段存在一些不足所致。
由美国食品与药品管理局批准的仅有的主要PDT剂是II型剂,porfimer钠(或PHOTOFRINTM)。基于卟啉的该药剂是一族相关药剂(如苯并卟啉衍生物,SnEt2,和黄体酮)的代表,该族药剂通常用单光子方式以波长为500纳米至730纳米的光来激活。该II型药剂由于氧通过光激活转换(光化学催化转换)变为不稳定的有毒形态(单线态氧)来杀灭有机体而产生疗效。不幸的是,这一过程要求在治疗部位有丰富的供氧。然而,供氧会很快耗尽,例如,因为供血受损(这一点在大肿瘤的中心是普遍的)或强烈的照射(会消耗所获的全部氧而阻断向单线态氧的持续转换)。因此,用这种药剂治疗大肿瘤并过度地使用照射法是不实际的。而且,象porfimer钠这种药剂通常须大剂量全身用药(通过静脉注射),尚需远在照射之前给药(一般情况下至少提前24小时——给患者增加了费用及不便)。再者,全身用药所需的大剂量是非常昂贵的(每剂高达5000美元或更多),而且会使皮肤产生对光的持久敏感。
基于卟啉的药剂的这些问题部分地源自这些药剂无法在肿瘤中达到足够的浓度。更确切地说,大剂量全身用药使所有组织均达到饱和。结果,经过几小时至数日的间隔之后,治疗部位的残余药剂的单光子激活不仅能在患病的组织中产生需要的细胞毒杀作用,而且也会因为其中也存在的药剂的激活而对外围的健康组织造成损害。也是该残留药剂使皮肤产生对光的持久敏感。此外,在未被光激活的情况下该族药剂意味着相当高的毒性(暗时对细胞产生的毒性)。光激活通常只是在一定程度上增大这一毒性(不良的明-暗细胞毒性比)。而对于这种药剂而言,双光子激活的应用能够改进PDT的效果,尤其是在实施照视法的过程中因为将TPE与具有已提高了生物靶向能力及明-暗细胞毒性的药剂配合而显著地扩大了PDT的安全性与效果并进而降低或消除潜在的间接损害。
然而,欲获得这些优点就要求确知靶的大小、位置和深度,以便TPE使用的光线准确地抵达靶的。这样,就要求有一个能够迅速而准确地对肿瘤或其他患病组织进行标识与定位的新方法。这样一种方法的附加特征应该能够解决PDT目前存在的其他问题,包括:使药剂的明-暗细胞毒性比得以提高(更准确地说是非常低的暗时细胞毒性);增加在患病组织与健康组织间具有强烈反差的药品在患病组织中的累积;以及使成像与治疗相结合(例如通过对在成像处的药品的光激活的方式)的能力。除此而外该方法的其他特征应包括显著降低药剂的费用以及能迅速地从正常组织中清除药剂。
因此,满足这些特征及克服当前使用的方法及药品中存在的不足就成为本项发明的一个目的。
发明内容
本项发明涉及至少使用一种PDT药剂时患病组织进行成像与治疗的方法及仪器。
本项发明的方法的一个具体实施例包括以下步骤:施以一种光激活药剂;该光激活药剂被留存于患病组织之中;用足够的光来激活患病组织中的光激活药剂以对患病组织进行治疗。
该光激活药剂优选是一种卤代夹氧蒽,如四碘四氯荧光素。
本项发明的方法的另一个实施例包括以下步骤:在成像之前或紧随其后对患者施以一种光激活药剂,该光激活剂留存于患病组织中;对患者进行成像以标识患病组织;用足够的光来激活已成像的患病组织中的光激活药剂以对已成像的患病组织进行治疗。
在另一个实施例中,光激活药剂可以作为CAT描扫,间接X光照相或相关医疗过程中的造影剂来使用。
在另一个实施例中,光激活药剂可以作为CAT描扫,间接X光照相或相关程序中的造影剂来使用,并且在患病组织中被光激活。
在另一个实施例中,光激活药剂可以作为MRI的造影剂来使用并可在患病组织中被光激活。
在此外的另一个实施例中,光激活药剂在使用之前要与MRI,CAT扫描,间接X光照相中相关的靶向剂或造影剂混合。
在本项发明的另一个实施例中,实施PDT的光源要与成像设备(如CAT扫描器,MRI,或相关的设备)集成或安装在一起。在另一个实施例中,该方法在能产生双光子激活的PDT/成像组合装置中使用了一个光源。在此外的又一个实施例中,PDT/成像组合装置中的光源可产生单光子激活。
根据本发明,提供了卤代夹氧蒽在制备用于为患病的组织成像的药剂中的用途,其中,在所述药剂中的所述卤代夹氧蒽的一部分能够留存在所述患病组织中;并且其中所述卤代夹氧蒽能够产生可检测的信号,以利用计算机轴向层析X光摄影法,间接X光照相法或磁共振成像法将所述患病组织形成造影并将其标识。
附图说明
图1a:四碘四氯荧光素的化学结构图;
图1b:一个卤代夹氧蒽的化学结构图;
图2:几个卤代夹氧蒽样品的双光子有效截面的图解;
图3:示出了装有四碘四氯荧光素、X光造影剂与对照剂的试管的CAT扫描图像;
图4:示出了图3中的一个浓度范围内的溶液的CAT扫描;
图5:卤素的能量与X光有效断面的关系曲线图;
图6:示出了根据本项发明的一台成像与治疗组合设备。
具体实施方式
本项发明涉及诊疗仪和在对患病组织进行成像和治疗的过程中至少一种药剂的使用。
本项发明的第一个实施例指的是光动力疗法的一个改进方法,可以通过一种具有优越的明-暗细胞毒性的光激活药剂的使用来增强效果。该实施例包括用光来激活患病组织中的光激活药剂使之杀灭患病组织进而达到对患病组织的治疗。该实例中包括的一个步骤是给患者施用一种光激活(PDT)药剂。该PDT药剂将更好地在患病组织中累积。这些步骤中的每一步骤,该PDT药剂以及以此为基础的本项发明的其他实施例将在下面作更为详细的讨论。
能在本项发明中使用的一个PDT药剂是四碘四氯荧光素(4,5,6,7-四氯-2′,4′,5′,7′-四碘荧光素);(见图1a之10)。四碘四氯荧光素是一种I型PDT药剂,以能在某些肿瘤及其他的患病组织(即靶的)中优先积累而著称。I型药剂通过直接的光化学转换变为有毒物质而产生对细胞的毒杀反应,而其I型光动力效应与氧完全无关。在有氧存在的情况下,四碘四氯荧光素也能高效地产生单线态氧(II型效应),进一步增强其光动力潜力。实际上,本申请的发明人已经发现,与常规的PDT药剂(如仅限于I型或II型结构效应之内的porfimer钠和其他基于卟啉的药剂)相比,四碘四氯荧光剂是一种非常有效的PDT药剂。例如,体外实验表明,经5秒之内的照射,浓度≤10μg/ml(微克/毫升)的四碘四氯荧光素能够杀死107个细菌/毫升。在相同条件下,仅杀灭这些细菌的百分之几,porfimer钠就需要几个小时的时间。因此,相对于porfimer钠而言,四碘四氯荧光素具有非常高的光致细胞毒性。而且,四碘四氯荧光素的暗时细胞毒性是微不足道的。因此,四碘四氯荧光素具有作为基于卟啉的PDT药剂的合格替代品的全部特征:卓越的生物靶向功能和很高的明-暗细胞毒性比。
四碘四氯荧光素是本发明选用的一类光激活药剂中的一个特例。这些药物被称为卤代夹氧蒽,在图1b中给出了图示,其中符号X,Y,和Z表示处于指定位置的不同元素,而符号R1和R2则表示在指定位置的不同的官能团。在附表1中对典型的卤代夹氧蒽的物理及光化学特性做出了概括。目前使用的最常见的PDT药剂porfimer钠也在表中列出,以便对相关特性作出比较。
总的来说,卤代夹氧蒽的特征是暗细胞毒性低,明细胞毒性高,单光子有效截面高,可从300纳米延伸至600纳米,而且其光化学特性明显地不受局部化学环境和在R1及R2位置附加功能衍生物的影响。此外,卤代夹氧蒽还将根据选择参与特性来靶向某些肿瘤或其他的患病组织。
卤代夹氧蒽瞄准特定组织或其他部位的功能可以通过在R1和R2的位置附加特定的功能衍生物进而改变药剂的化学参与或生物活性的方式来加以优化。例如,在R1或R2的位置加入一个或多个起靶向作用的部分就能改进对特定组织如癌瘤组织或局部感染部位的靶向能力。这些起靶向作用的部分包括DNA(脱氧核糖核酸),RNA(核糖核酸),氨基酸,蛋白质,抗体,配体,半抗原,碳水化合物受体或络合剂,类脂体受体或络合剂,蛋白质受体或络合剂,螯合剂,以及包封载体。
使四碘四氯荧光素与一个类脂体结合(通过在R1位置酯化作用)以增强四碘四氯荧光素的亲脂性能,借此在容许的范围内来修饰其靶向特性,就是该特征的一个例子。这种经过修饰的药剂可以作为一种胶态离子悬浮液来直接给药,或者与一个释放载体如表面活性剂一起释放,并能够显示出其已经增强的对肿瘤细胞的靶向能力。适合该药剂的剂型包括局部施用的霜剂与洗剂,和静脉施用的,不经肠胃施用的或肿瘤内施用的注射液。
除了具有所要求的SPE特征外,卤代夹氧蒽还可提供用于TPE的引人注目的性能。尤其是,如图2中所示,该类药剂能够在从大于730纳米直至小于1100纳米的波长伸展范围内提供广泛而强烈的TPE光谱反应。更确切地说,作为一个例子,添加在R1及R2位置的部分并未引起TPE光谱特性的明显变化,这通过对曙红Y(这里R1=Na)和乙基曙红(这里R1=OCH2CH3)的光谱响应作出比较就一目了然。因而,添加靶向药剂又不明显影响药剂的光化学性能是可能的。
因此,卤代夹氧蒽成为SPE及TPE激活方式的优秀PDT药剂,并且可以直接使用,或者提高了溶解度或生物靶向能力的衍生物形式来使用,例如,这可以通过在R1及R2位置添加不同的官能团来实现。因此,在本项发明所选的一个实施例中,至少有一种卤代夹氧蒽或其衍生物是作为PDT药剂来使用。该PDT药剂可以以业内熟知的方式,如口服,全身用药(如通过注射),或者局部用药的方式来给药。四碘四氯荧光剂作为PDT药剂来使用是更好的选择。该药剂可以用单光子激活的方式来激活,或者,当然更好,用双光子方式。
在本项发明的另一个实施例中,通过使用常规的成像方法来标识患病的组织靶的,使光致激活的选择性得到了提高。例如,以X光为基础的成像如计算机轴向层析X光摄影法(CAT扫描),间接X光照相法或者其他相关的方式,或者是磁共振成像法(MRI),均可用于检测患病组织的位置。这样的成像通过对组织成分(如密度)的分布或功能中的异常,某些物质的存在或消失,或者成像造影剂的吸收或排斥情况的探测来进行。然后该患病组织被用作给患者服用的光动力剂选用的光激活的靶的,借此有选择地杀灭该患病组织。
本项发明的发明人发现某些PDT药剂,而更确切地说是卤代夹氧蒽,并没有被明显地以光动力的方式激活,也没有因暴露在X光或MRI成像所共用的能量之下而失效。因此,这些药剂在该诊断过程之前对服用者是安全的。这样,PDT药剂是可以在诊断之前(这样就可以缩短诊断与治疗之间的时间延迟)或者随诊断之后(这样,就可降低在未检测出病患的情况下的不必要的服药)服给患者的。
因此,本项发明所选的一个实施例包括的步骤有以常规方式进行X光或MRI成像以检测患病组织的存在;服用PDT药剂,最好是卤代夹氧蒽,在对该患病的组织进行检测之前或结束检测后立即服用,并且把适于SPE或者最好是TPE激活方法的光,象下面讨论的那样,射向检测出的患病组织或射到其上面,要足以激活该PDT药剂,并借此有选择地显著地但仅是摧毁该患病组织。
在本发明的另一个实施例中,通过成像造影剂的使用使前一个实施例中的检测或成像步骤的功效得到进一步的改进。特别是PDT药剂,更确切地说是卤代夹氧蒽,要与一个成像造影剂混合,如,以X光造影剂为例,象欧乃哌克TM(碘海醇)和OmniscanTM(加多米特),或者各种各样的MRI造影剂的一种,象DPTA钆(Gd-DPTA).例如,四碘四氯荧光素在溶解状态下与诸如欧乃哌克TM、OmniscanTM和DPTA钆这样的药剂是相容的,并显示出相同的生物靶向特性。然后,将这种混合剂服给患者。服用这种造影剂与PDT药剂的混合剂后,用常规的成像法(如,以CAT扫描或MRI为例)根据常规造影剂的反应对患病组织进行定位,然后,用SPE或者更好是用TPE将共同位于患病组织中的PDT药剂在患病组织所在的部位激活,以摧毁该患病组织。
发明人指出,在肝脏模型中,服用该药溶液之后四碘四氯荧光素能够选择性的光动力激活。这种模型用于累积常规的X光及MRI造影剂方面也是人们熟知的。因此,发明人指出,向目标组织释放常规的成像造影剂和PDT药剂是可行的,而且这些药剂将在目标组织中保留各自的活性,这样就可以对处于根据检测到的形像造影剂进行成像所指明的位置的患病组织进行组合的探测和治疗。因此,本发明的一个优选实施例就是联合服药,或者是连续地服用(如通过注射或静脉内点滴),或者最好是以单一的混合溶液的形式服用,一种或多种X光或MRI造影剂与一种或多种PDT药剂最好是卤代夹氧蒽药剂混合,然后根据用一个或多个造影剂获得的成像数据直接激活一个或多个PDT药剂。
在本项发明的另一个实施例中,PDT药剂还起成像造影剂的作用。成像与治疗过程使用同一药剂具有很高的优越性。例如,一种药剂就没有必要再服第二剂。第二剂药要求在成像与治疗之间有更多的时间,因为象第二种药一样在服用之后,在治疗可以开始之前必须在患病组织中累积。而且,用第二种药会使治疗更昂贵,并使患者再次遭受体外异物的作用。
更确切地说,因为有充分的卤素含量,卤代夹氧蒽的化学结构的电子密度就高,因而对X光线不透明。例如,四碘四氯荧光素就能够高度遮挡用于CAT扫描或常规X光成像的X光线。图3与图4示出了四碘四氯荧光素的不透明度与标准的X光造影剂和对照剂的关系曲线。这些图是根据本发明的发明人所作的实验的实际图片画出的。例如,图3中所示的装有不同溶液的试管的CAT扫描图像表明,碘40(350毫克碘/毫升,水溶液),四碘四氯荧光素42(225毫克卤素/毫克,盐水溶液),和欧乃哌克TM44(350碘/ml碘海醇)都有相同的X光密度。而且,这些密度明显地高于对照剂46(盐水)的密度。图4中示出了这些相同溶液的不同稀释度的样品(装在一个96孔样品板的孔中)的一个CAT扫描图像,该图说明在一个浓度范围内四碘四氯荧光素42的响应度与标准的X光造影剂40,44的响应度不相上下。
图5表明,在远低于标准的X光诊断设备使用的能量水平的情况下卤素的强烈吸收,标准的X光诊断设备通常使用大于50KeV(千电子伏)的能量。因此,卤代夹氧蒽的卤素含量使该类光动力剂成为有效的X光造影剂。由于X光的有效截面依F<Cl<Br<I(F:氟;Cl:氯;Br:溴;I:碘)的顺序显著增强,碘或溴含量高的那些卤代夹氧蒽用作X光的造影剂成为优选。例如,表1表明,由于各自在卤素含量上的差别,四碘四氯荧光素、Phloxine B、藻红B、和曙红Y的X光有效截面要大于亚加红或曙红B,因此将被优选为X光造影剂来使用。更优选的是,高碘含量的四碘四氯荧光素使该药成为这类药剂中最具吸引力的X光造影剂。
这样,某些特定的PDT药剂,尤其是卤代夹氧蒽,可以作为造影剂用于基于X光的为了检测疾病而对组织进行的检测和成像。这是基于这种药剂的组织特性以及它们的X光密度大的原因。因此,用这种药剂作为X光的造影剂更是一个优选的实施例。
在这样的使用条件下这种药剂通常能够保持其光动力能力,因此可以用于基于X光的对患病组织的检测,然后用SPE或者最好是用TPE激活法来引导成像的光动力激活,进而有选择地摧毁患病的组织。由于卤化夹氧夹蒽的碘或溴的含量大,它们的X光密度和光动力效应均为最大,因此,这些药剂对于把X光成像与随后的根据成像结果对特定部位进行PDT激活这两个过程组合起来而言是最佳选择。例如表1表明,四碘四氯荧光素,Phloxine B、藻红B、和曙红Y在单线态氧的生成上具有高效,并且也是极度高效的PDT剂。这样,本项发明的一个更为优选的实施例是,用卤代夹氧蒽,最好是选碘化或溴化的卤代夹氧蒽作为组合的X光反差和PDT药剂,其中X光成像用于导引随后的用SPE或最好是用TPE激活方法对该药剂的激活。
除了前面提到的把卤代夹氧蒽作为X光造影剂来使用之外,这些药剂独特的结构特征使其成为MRI造影剂的颇具吸引力的候选。虽然并非像大多数常规MRI造影剂那样是顺磁性的,但是卤代夹氧蒽含有芳烃质子,在该质子的化学漂移方面展示出其具有特色的MRI特征。而且,由于卤代夹氧蒽中存在密度相当大的芳烃卤素,使其在检测来自这些芳烃卤素的共振上具有更为独特而有用的MRI特征。由于质子及卤素的核磁共振是相当敏感的现象(例如,表2中所示,与碳-13NMR(核磁共振)相比,氟、溴和碘有着高出许多倍的敏感性),根据患病组织中卤代夹氧蒽的存在进行的MRI检测与成像代表了该药剂的更为独特与颇具吸引力的医学应用。因此,本项发明的又一个优选实施例是把卤代夹氧蒽作为MRI造影剂来应用,并且用根据对这种药剂的检测得到的成像数据有选择地引导后续的对存在于患病组织中的这种药剂进行的光激活,用的是SPE而且最好是TPE激活光法。由于大多数已安装的MRT设备是基于对质子共振进行检测,那么根据存在于卤代夹氧蒽中的芳烃质子的共振来进行这种MRI检测就成为又一个优选。
紧随本项发明中的成像之后,通过一个光源把光加至患病部位以便用光把与患病组织结合的该药剂激活。最好使用激光。替代的光源包括发光二极管,微型激光器,用以产生激活光的单色或连续激光器或灯泡,以及连续波或脉冲激光器或灯泡。或者是单光子激活方法,或者是双光子激活方法,都可用于药剂的激活。这种激活方法的更为详细的解释在于1996年10月30日提出的08/739,801号共同转让的申请中给出,这里引用以作为参考。光激活药剂的激活开始了一个最后将杀灭患病组织中的细胞的过程。
在本项发明的另一个实施例中,用于光动力激活的光源被集成到成像设备如一个MRI系统或X光成像设备之中或之上。图6中给出了用于成像和治疗的这样一台设备的例子50。这种组合的成像与治疗设备由于改进了成像数据与治疗目标之间的读数的精度,能使治疗更准确地抵达患病组织。例如,图6展示出了一部常规的成像单元52,比如是一个CAT扫描或MRI系统,用于标定患者56体内存在的疾患54。该疾患的成像可以通过前面讨论过的方法或者其他已知的成像方法来完成。然后,该疾患54作为一个集成的激活单元58的靶的,该激活单元用于有选择地光激活存在于疾患中的PDT药剂。激活单元58优选包括一个光源60,例如一个能对该药剂实施SPE激活的激光器,而最好地是一个对该药剂实施TPE激活的激光器如一个锁模钛蓝宝石或钕YLF激光器。最好,激活单元58还包括一个瞄准系统62,如一个镜基的电流计或其他的光学扫描系统。以这种方式制造及运行,成像单元52就可以用来控制由激活单元58产生的光64的施加,例如,由医生进行手动控制或者最好是自动或半自动的计算机控制,这样,激活光64实质上只施加到检测到的疾患54的部位,借此改善治疗过程的安全性与有效性。
锁模钛蓝宝石激光器是集成的激活单元的光源的优选实施例。这样的激光器能产生快速的NIR光的系列高峰功率脉冲,非常适合于卤代夹氧蒽的TPE。标准的,市场上可以买得到的锁模钛蓝宝石激光器能够输出时间间隔小于200fs(fs:飞秒,10-15秒)的锁模脉冲,脉冲能量约为1-20nJ(nJ:纳焦耳),脉冲重复频率超过75MHz。这就产生了具有相当低的平均功率(最高可达几瓦)但尖峰功率高(约为100千瓦)的准连续光束,该光束在接近690-1080nm的NIR波长带上可以连续调节。由该光源生成的脉冲序列易于用标准的光学方法如反射或折射光学的方法来瞄准,以便被引至一个疾患或其他的局部治疗目标。适合于光动力药剂的激活的其他光源包括:连续波和脉冲式灯,二极管光源,半导体激光器;其他类型的气体、染料与固态的连续的、脉冲式的或销模式的激光器,包括:氩离子激光器,氪离子激光器,氦氖激光器,氦镉激光器,红宝石激光器;ND:YAG,ND:YLF,ND:YAP,Nd:YVO4,Nd:GLASS,和Nd:CrGsGG激光器;Cr:LiSF激光器;Er:YAG激光器;F-center激光器;Ho:YAF和Ho:YLF激光器;铜蒸气激光器;氮激光器;光学参量振荡器,放大器与发生器;再生放大激光器;线性调频脉冲放大激光器;和日光。
这些描述只是为了举例说明,并不是对本发明的限制,本发明的范围由权利要求书限定。
权利要求书中提出了本发明新的且希望予以保护的方案。
Claims (8)
1.卤代夹氧蒽在制备用于为癌病变组织成像的药剂中的用途,
其中,在所述药剂中的所述卤代夹氧蒽的一部分能够留存在所述患病组织中,所述卤代夹氧蒽选自一个组,该组包括分子量为1018g的二钠四碘四氯荧光素、分子量为830g的二钠焰红染料B、分子量为880g的二钠藻红B、和分子量为692g的二钠曙红Y;
并且其中所述卤代夹氧蒽能够产生可检测的信号,以利用计算机轴向层析X光摄影法,间接X光照相法或磁共振成像法将所述患病组织形成造影并将其标识。
2.权利要求1的用途,其中所述卤代夹氧蒽作为一个功能衍生物包括一个靶向部分,该部分选自一个组,该组包括DNA,RNA,氨基酸,蛋白质,抗体,配体,半抗原,碳水化合物受体或络合剂,类脂体受体或络合剂,蛋白质受体或络合剂,螯合剂,以及包封载体。
3.权利要求1的用途,其中所述卤代夹氧蒽与常规的成像造影剂混合生成一种混合剂,而后给患者服用所述混合剂。
4.权利要求3的用途,其中所述常规成像造影剂选自一个组,该组包括OmnipaqueTM(碘海醇),OmniscanTM(加多米特),和各种顺磁性的MRI造影剂中的一种,其中包括DPTA钆(Gd-DPTA)。
5.权利要求3的用途,其中所述常规成像造影剂是一个X光造影剂。
6.权利要求3的用途,其中所述常规成像造影剂是一个MRI造影剂。
7.权利要求1的用途,其中由所述卤代夹氧蒽产生可检测的信号是依据所述卤代夹氧蒽中的芳烃质子的共振进行的。
8.权利要求1的用途,其中由所述卤代夹氧蒽产生可检测的信号是依据所述卤代夹氧蒽中的芳烃卤化物的共振进行的。
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DE69938870D1 (de) | 2008-07-17 |
WO2000025665A1 (en) | 2000-05-11 |
JP2002528472A (ja) | 2002-09-03 |
IL142729A0 (en) | 2002-03-10 |
ES2307344T3 (es) | 2008-11-16 |
EP1126782B1 (en) | 2008-06-04 |
US6493570B1 (en) | 2002-12-10 |
CA2348094A1 (en) | 2000-05-11 |
EP1126782A4 (en) | 2003-06-04 |
AU1452100A (en) | 2000-05-22 |
HK1040899A1 (en) | 2002-06-28 |
KR20010080932A (ko) | 2001-08-25 |
HK1040899B (zh) | 2008-12-24 |
CN1325284A (zh) | 2001-12-05 |
EP1126782A1 (en) | 2001-08-29 |
ATE397408T1 (de) | 2008-06-15 |
BR9914969A (pt) | 2001-07-10 |
AR021061A1 (es) | 2002-06-12 |
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