5-[123I/125I]iodo-2'-deoxyuridine in metastatic lung cancer: radiopharmaceutical formulation affects targeting.
5-[123I/125I]iodo-2'-deoxyuridine in metastatic lung cancer: radiopharmaceutical formulation affects targeting.
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发表时间：
2005-05
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通讯作者：
Elham Safaie Semnani;Ketai Wang;S. Adelstein;A. Kassis
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作者：
Elham Safaie Semnani;Ketai Wang;S. Adelstein;A. Kassis
未标记本研究评估了放射性碘标记胸苷类似物5-[（123）I/（125）I]碘-2 '-脱氧尿苷（（123）I-IUdR/（125）I-IUdR）对小鼠肺转移瘤的靶向作用，该类似物与不同量的三丁基锡前体配制并静脉注射。方法6 ~ 8周龄C57 BL/6小鼠静脉注射B16 F10黑色素瘤细胞。两周后，当建立肺肿瘤时，在氧化剂存在下，用1、35、100、150、200或250微克5-三丁基甲锡烷基-2 '-脱氧尿苷（SnUdR）合成的（125）I-IUdR静脉注射动物。非荷瘤小鼠也注射这些制剂，并作为对照动物。24小时后，将动物处死，并在γ计数器中测量与肺和其他组织相关的放射性。计算每克组织的注射剂量百分比（%ID/g）和肿瘤与非肿瘤比率（T/NT比率）。对荷瘤和非荷瘤小鼠的肺进行磷光体成像，这些小鼠注射了用每种锡前体浓度配制的（125）I-IUdR。静脉注射123 I-IUdR后3 h和24 h行闪烁显像。结果荷瘤动物肺组织中%ID/g（125）I-IUdR含量高于对照动物肺组织。尽管SnUdR的增加导致正常肺的放射性含量的小但统计学显著的降低，但在具有100 μ g SnUdR（每只小鼠5 μ g）配制的放射性药物的荷瘤动物的肺中观察到3倍的增加。肺放射性摄取的这种增强导致T/NT比率增加约14倍。肺的磷显像（（125）I-IUdR）以及整个动物的肺造影（（123）I-IUdR）证实了这些发现。结论确定了放射性IUdR合成的最佳T/NT比和最高肿瘤%ID/g的配方。需要进一步研究以确定负责IUdR肿瘤摄取的特异性增强的因素。
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.