title: 5-[123I/125I]iodo-2'-deoxyuridine in metastatic lung cancer: radiopharmaceutical formulation affects targeting.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Elham Safaie
authors.initials: ES
authors.lastname: Semnani
authors.forename: Ketai
authors.initials: K
authors.lastname: Wang
authors.forename: S James
authors.initials: SJ
authors.lastname: Adelstein
authors.forename: Amin I
authors.initials: AI
authors.lastname: Kassis
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D007065:Idoxuridine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007553:Isotope Labeling / Q000379:methods; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D011874:Radiometry / Q000379:methods*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D014018:Tissue Distribution; D014915:Whole-Body Counting
chemical_list: D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D007065:Idoxuridine