Pimm M V, Perkins A C, Gribben S J, Mezö G, Gaál D, Hudecz F
Cancer Research Laboratory, University of Nottingham, UK.
Ann Nucl Med. 1995 Nov;9(4):247-51. doi: 10.1007/BF03168409.
Radiolabelled synthetic branched chain polypeptides (BCP) represent a new and novel range of materials with potential as radiopharmaceuticals. Preliminary imaging studies have been undertaken with 111In-labelled BCP in mice with subcutaneously transplanted mammary carcinoma. Four polypeptides each with a poly(L-lysine) backbone and side chains of DL-alanine residues were studied. These were AK, which is polycationic, EAK which is amphoteric, having additional glutamic acid residues at the end of the side chains, and AcEAK (anionic) and SucEAK (highly polyanionic) where the terminal glutamic acid amino groups were acetylated or succinylated respectively. Radiolabelling was achieved by previous conjugation with DTPA. Serial images up to 48 hours showed marked retention of 111In-labelled polycationic AK and polyanionic SucEAK in the liver and spleen, with renal uptake also being visible in the case of AK. 111In-labelled EAK and AcEAK showed longer blood survival with some liver uptake, but tumour uptake was also visualized by 24 hours with both of these polypeptides. These studies demonstrate the feasibility of using 111In-labelled synthetic branched chain polypeptides as radiopharmaceuticals for gamma scintigraphy and the visualization of tumours by modification of the side chain structure. These materials warrant further study.
放射性标记的合成支链多肽（BCP）代表了一类新型的具有作为放射性药物潜力的材料。已对皮下移植了乳腺癌的小鼠进行了用¹¹¹In标记的BCP的初步成像研究。研究了四种多肽，每种多肽都具有聚（L-赖氨酸）主链和DL-丙氨酸残基侧链。这些多肽分别是带正电的AK、两性的EAK（在侧链末端有额外的谷氨酸残基）、AcEAK（带负电）和SucEAK（高度带负电），其中末端谷氨酸氨基分别被乙酰化或琥珀酰化。通过先前与二乙三胺五乙酸（DTPA）偶联实现放射性标记。长达48小时的系列图像显示，¹¹¹In标记的带正电的AK和带负电的SucEAK在肝脏和脾脏中有明显滞留，对于AK来说，肾脏也有摄取。¹¹¹In标记的EAK和AcEAK在血液中的存留时间更长，有一些肝脏摄取，但这两种多肽在24小时时也都能看到肿瘤摄取。这些研究证明了使用¹¹¹In标记的合成支链多肽作为放射性药物用于γ闪烁显像以及通过修饰侧链结构来实现肿瘤显像的可行性。这些材料值得进一步研究。
