99mTc-Ethylenedicysteine-guanine

Excerpt

Evaluation of tumor malignancy and growth potential is important for the assessment of cancer treatment. For this evaluation, the uptake of indicators such as ¹⁸F-labeled 2’-fluorodeoxyglucose (¹⁸F-FDG) is often used to monitor the effectiveness of a treatment because ¹⁸F-FDG was shown to be related to the number of viable cells present in a tumor (1, 2). In addition, a variety of labeled amino acids have also been used to determine the proliferative potential of neoplastic cells and tumors (3, 4). Although these compounds determine the proliferation of viable cells, none of them are incorporated into the cellular DNA and can not determine the true state of tumor malignancy and proliferative potential. Because labeled purine- and pyramidine-based compounds can be incorporated into DNA, these agents can be employed to determine tumor malignancy and proliferative potential, and to evaluate the efficacy of or response to a treatment. However, a variety of ¹⁸F-labeled pyrmidine or purine compounds have been used primarily to image the expression of reporter genes such as the wild-type or mutant herpes simplex virus type I thymidine kinase (HSV1-tk) (5, 6). The thymidine kinase enzyme (TK) produced from HSV-tk phosphorylates many different substrates, including acycloguanines. Because mammalian TK is known to minimally phosphorylate acycloguanines, this makes such compounds useful only for the imaging of reporter genes (6).

To assess the efficacy of tumor therapy, it is important to have an agent that interacts primarily with the endogenous TK and measures only cell proliferation. Different isotopes of carbon (¹¹C), iodine (^123/125I), or fluorine (¹⁸F) have been employed to generate labeled thymidine or uracil for the investigation of cell proliferation because these compounds are incorporated into cellular DNA or RNA (7-9). Nonetheless, these compounds have limited use either because of the complex chemistry involved in their synthesis, short isotope half-life, or stability issues. Because technetium (^99mTc) has a longer half-life than ¹¹C, ^123/125I, or ¹⁸F, Yang et al. synthesized a ^99mTc-labeled guanine (a purine) analog that contains ethylenedicysteine (EC) as a chelator of ^99mTc (10). Subsequently, ^99mTc-EC-guanine (^99mTc-EC-guan) was investigated for the biodistribution and assessment of tumor growth in rodents (10).