Radioiododeoxyuridine in cancer therapy: an in vitro approach to developing in vivo strategies.
Studies were undertaken to determine the relationship between IUdR concentration and the duration of radiolabeled IUdR treatment required to incorporate the equivalent of a D(o) dose in vitro and to estimate the treatment parameters necessary to incorporate a killing dose in vivo.


METHODS
W138 (normal human) and HeLa (human cancer) cells were grown axenically or in co-culture. The three cultures were treated for 5 days with 18.5 kBq/ml [125I]IUdR. After treatment, the cells were subcultured and grown for 7 days in medium without [125I]IUdR. In separate experiments, Chinese hamster ovary cells (CHO) were labeled with various ratios of radiolabeled (125I) and nonradiolabeled IUdR and the mole rate of IUdR incorporation in double-stranded DNA was measured. Mitotically selected CHO cells were incubated without treatment until > 98% were in S phase. At this time, the cells were labeled for 15 min with several concentrations of either [123I]IUdR or [125I]IUdR and their colony survival was measured.


RESULTS
After incubation with [125I]IUdR, selective eradication of HeLa cells from a co-culture of W138 and HeLa cells was achieved. The incorporation of IUdR into DNA of CHO cells, although the sum of a series of enzymatic steps, has the appearance of and can be analyzed as a Michaelis-Menton type curve. The maximum rate of IUdR incorporation (Vmax) is 4.424 x 10(-18) mol/min and the substrate concentration at 1/2 Vmax (K) is 3.717 x 10(-6) M IUdR. The Do dose rates for [123I]IUdR and [125I]IUdR, respectively, are 18.78 and 1.88 initial decays/cell/hr.


CONCLUSIONS
The D(o) dose for *IUdR can be determined from survival curves versus the mole amount of *IUdR incorporated in DNA. To be effective as an in vivo treatment it will be necessary to manipulate the IUdR delivery time, concentration and volume in a manner that assures that the target cells incorporate a cytocidal dose of *IUdR.
Schneiderman
M H
MH
Department of Radiology, J. Bruce Henriksen, MD, Cancer Research Laboratories, University of Nebraska Medical Center, Omaha, USA.
Schneiderman
G S
GS
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured / Q000528:radiation effects; D006224:Cricetinae; D006801:Humans; D007065:Idoxuridine / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D011829:Radiation Dosage; D014407:Tumor Cells, Cultured / Q000528:radiation effects
D007457:Iodine Radioisotopes; D007065:Idoxuridine