Radiolabelled 5 '-iodo-2 '-deoxyuridine: A promising alternative to [F-18]-2-fluoro-2-deoxy-D-glucose for PET studies of early response to anticancertreatment

We investigated the potential of radiolabelled 5 iodo-2'-deoxyuridine (IUdR ) as a pharmacodynamic probe for use with positron emission tomography (PET ) in studies of early proliferative response to anticancer treatment. Using the hormone-responsive rat mammary carcinoma OES.HR1, we used a multiple r adiotracer method to examine treatment-induced changes in 24 h tumour reten tion of [I-131]IUdR, uptake of [H-3]2-deoxy-D-glucose ([H-3]DG) together wi th [Tc-99m]hexylmethylpropylene amineoxine ([Tc-99m]HMPAO) uptake as a meas ure of blood flow. Radiotracer data were compared with macroscopic changes in tumour growth, and cell proliferation as determined by DNA histogram flo w cytometry. From 4 days after tumour growth arrest induced by oestrogen ab lation, a sustained fall in tumour cell proliferation was demonstrated, whi ch was associated with reduced tumour uptake of each tracer. Whereas reduce d levels of tumour [3H]DG could be accounted for by changes in blood flow, this was not the case for [I-131]IUdR, which was found to be closely relate d to percentage S-phase cells within tumour (r = 0.73, p < 0.002). It was a lso estimated that residual levels of radioiodide may contribute significan tly to the low levels of retained radioactivity associated with responding tumours at 24 h following IUdR administration, suggesting that metabolite c orrection methods should be implemented as part of IUdR PET imaging protoco ls. We conclude that [I-124]IUdR is a promising alternative to [ F-18]fluor odeoxyglucose ([F-18]FDG) for the early assessment by PET of tumour respons e to treatments directed at targets associated with cell proliferation. NUC L MED BIOL 26;6:667-672, 1999. (C) 1999 Elsevier Science Inc. All rights re served.