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5-[¹²³I/¹²⁵I]Iodo-2'-Deoxyuridine in Metastatic Lung Cancer: Radiopharmaceutical Formulation Affects Targeting

Department of Radiology, Harvard Medical School, Boston, Massachusetts

This study assesses targeting of lung metastases in mice with the radioiodinated thymidine analog 5-[¹²³I/¹²⁵I]iodo-2'-deoxyuridine (¹²³I-IUdR/¹²⁵I-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 ¹²⁵I-IUdR synthesized using 1, 35, 100, 150, 200, or 250 µg 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 -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 ¹²⁵I-IUdR formulated with each tin precursor concentration. Scintigraphy was also performed 3 and 24 h after intravenous injection of ¹²³I-IUdR. Results: The %ID/g ¹²⁵I-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 µg SnUdR (5 µg per mouse). This enhancement in radioactive uptake by the lungs led to approximately 14-fold increases in T/NT ratios. Phosphor imaging (¹²⁵I-IUdR) of lungs as well as scintigraphy (¹²³I-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.

Key Words: 5-[¹²³I/¹²⁵I]iodo-2'-deoxyuridine • metastatic lung cancer • 5-tributylstannyl-2'-deoxyuridine • tumor targeting

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JNM 2005 46: 8a-9a. [Full Text]