ABSTRACT
UNLABELLED: This study assesses targeting of lung metastases in mice with the radioiodinated thymidine analog 5-[(123)I/(125)I]iodo-2'-deoxyuridine ((123)I-IUdR/(125)I-IUdR), formulated with varying amounts of tributyltin precursor and injected intravenously. METHODS: Six- to 8-wk-old C57BL/6 mice were injected intravenously with B16F10 melanoma cells. Two weeks later, when lung tumors were established, the animals were injected intravenously with (125)I-IUdR synthesized using 1, 35, 100, 150, 200, or 250 microg 5-tributylstannyl-2'-deoxyuridine (SnUdR) in the presence of an oxidant. Nontumor-bearing mice were also injected with these formulations and served as control animals. Twenty-four hours later, the animals were killed, and the radioactivity associated with the lungs and other tissues was measured in a gamma-counter. The percentage injected dose per gram tissue (%ID/g) and tumor-to-nontumor ratios (T/NT ratios) were calculated. Phosphor imaging was done on lungs from tumor-bearing and nontumor-bearing mice injected with (125)I-IUdR formulated with each tin precursor concentration. Scintigraphy was also performed 3 and 24 h after intravenous injection of (123)I-IUdR. RESULTS: The %ID/g (125)I-IUdR was higher in lungs of tumor-bearing animals than in lungs of control animals. Although the increase in SnUdR present led to a small but statistically significant decrease in the radioactive content of normal lungs, a 3-fold increase was observed in the lungs of tumor-bearing animals with radiopharmaceutical formulated with 100 microg SnUdR (5 microg per mouse). This enhancement in radioactive uptake by the lungs led to approximately 14-fold increases in T/NT ratios. Phosphor imaging ((125)I-IUdR) of lungs as well as scintigraphy ((123)I-IUdR) of whole animals substantiated these findings. CONCLUSION: The formulation for the synthesis of radio-IUdR that leads to the highest %ID/g in tumor and the best T/NT ratio has been identified. Further studies are required to determine the factors responsible for specific enhancement in IUdR tumor uptake.
Subject(s)
Drug Delivery Systems/methods , Idoxuridine/pharmacokinetics , Iodine Radioisotopes/pharmacokinetics , Lung Neoplasms/metabolism , Melanoma/metabolism , Melanoma/secondary , Radiometry/methods , Animals , Idoxuridine/therapeutic use , Iodine Radioisotopes/therapeutic use , Isotope Labeling/methods , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/radiotherapy , Male , Melanoma/diagnostic imaging , Melanoma/radiotherapy , Mice , Mice, Inbred C57BL , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Radiopharmaceuticals/therapeutic use , Radiotherapy Dosage , Tissue Distribution , Whole-Body CountingABSTRACT
PURPOSE: To assess the therapeutic potential of methotrexate (MTX) and 5-[1251]liodo-2'-deoxyuridine (125IdUrd) administered sequentially in rats bearing advanced (ten-day-old) intrathecal (i.t.) TE671 human rhabdomyosarcoma tumours. MATERIALS AND METHODS: Nude rats were injected with TE671 cells through an i.t. placed catheter. Ten days later, the animals were injected i.t. over a 12-day period with (i) saline daily, (ii) MTX every other day, (iii) 125IdUrd every other day, or (iv) MTX and 125IdUrd on alternating days. Onset of paralysis was determined as a function of time, and the medians for onset (M), percentage of cells killed (% kill), and log cell kill were calculated. RESULTS: The data show that (i) injection of MTX leads to a moderate delay in the onset of paralysis (M(MTX) = 29 d versus Msaline = 20 d), (ii) administration of 125IdUrd is more effective (M(IdUrd) = 36 d), and (iii) sequential administration of MTX- 125IdUrd further increases the therapeutic efficacy of 125IdUrd (M(MTX)-IdUrd = 47 d). CONCLUSIONS: Intrathecal injection of MTX-(125)IdUrd is efficacious in the therapy of advanced intrathecal tumours.
