人精子中发射俄歇电子的诊断性放射性核素的转铁蛋白依赖性摄取及剂量测定

Transferrin-dependent uptake and dosimetry of Auger-emitting diagnostic radionuclides in human spermatozoa.

作者信息

Hoyes K P, Nettleton J S, Lawson R S, Morris I D

机构信息

School of Biological Sciences, University of Manchester, and Manchester Royal Infirmary, United Kingdom.

出版信息

J Nucl Med. 1998 May;39(5):895-9.

PMID:9591597

Abstract

UNLABELLED

Localization of Auger-emitting radionuclides within spermatozoa could lead to the induction of transmissible genetic damage. We have quantified in vitro uptake of the widely used diagnostic Auger-emitters, (111)In and 99mTc, by ejaculated human spermatozoa and investigated the role of transferrin in their cellular localization. The resultant dose to sperm heads, including cellular dosimetry for Auger emissions, has been calculated for each radionuclide and compared with that achieved using conventional macrodosimetry.

METHODS

Freshly isolated human spermatozoa were incubated in a physiological salt solution containing (111)In-chloride, 99mTc-pertechnetate or the transferrin-binding isotope 59Fe-citrate as a positive control. Cellular uptake mechanisms were investigated with transferrin competition and temperature dependence studies. The percentage uptake of each radionuclide was determined, and the dose to individual sperm heads was calculated using both conventional macrodosimetric methods and by consideration of radionuclide localization and energy deposition at the cellular level, including Auger electron emissions from (111)In and 99mTc.

RESULTS

On in vitro incubation, human spermatozoa were found to accumulate (111)In and 59Fe but not 99mTc. Cell uptake of (111)In and 59Fe was transferrin-mediated; however, an alternative transferrin-independent uptake pathway was also present for (111)In. The dose to sperm heads from (111)In, calculated using measured uptake and cellular dosimetry, was found to be larger than that calculated using conventional dosimetry by a factor of more than 100. In contrast, conventional dosimetry was adequate for 99mTc and 59Fe.

CONCLUSION

Isolated human spermatozoa appear to accumulate transferrin-binding isotopes, such as the Auger-emitter (111)In. If this uptake mechanism operates in the male reproductive tract, the resultant high dose to the sperm head could indicate that contraception may be advisable after large diagnostic doses of (111)In and, possibly, other transferrin-binding radionuclides. Such precautions could prevent transmission of any genetic damage from irradiated spermatozoa.

摘要

未标记

俄歇发射放射性核素在精子内的定位可能导致可传播的遗传损伤。我们已对射出的人类精子对广泛使用的诊断性俄歇发射体（111）铟和99m锝的体外摄取进行了定量，并研究了转铁蛋白在其细胞定位中的作用。已针对每种放射性核素计算了精子头部的所得剂量，包括俄歇发射的细胞剂量学，并与使用传统宏观剂量学所获得的剂量进行了比较。

方法

将新鲜分离的人类精子在含有氯化（111）铟、高锝酸盐99m锝或转铁蛋白结合同位素柠檬酸铁59作为阳性对照的生理盐溶液中孵育。通过转铁蛋白竞争和温度依赖性研究来研究细胞摄取机制。测定每种放射性核素的摄取百分比，并使用传统宏观剂量学方法以及考虑细胞水平上的放射性核素定位和能量沉积（包括来自（111）铟和99m锝的俄歇电子发射）来计算单个精子头部的剂量。

结果

在体外孵育时，发现人类精子会积累（111）铟和59铁，但不会积累99m锝。（111）铟和59铁的细胞摄取是由转铁蛋白介导的；然而，（111）铟也存在另一种不依赖转铁蛋白的摄取途径。使用测量的摄取量和细胞剂量学计算得出，（111）铟对精子头部的剂量比使用传统剂量学计算得出的剂量大100多倍。相比之下，传统剂量学适用于99m锝和59铁。