ABSTRACT
In this study,a novel technique for the preparation of 125I-5-trimethylstannyl1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) urail (FIAU) was developed,125I-FIAU biodistribution profile was detected in Kunming mice and the possibility of using FTAU radio-labeling for reporter gene imaging was explored.5-trimethylstannyl-l-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) urail.(FTAU) was labeled with radioiodine (125I).A rotary evaporation method was used to remove excess methanol.The reactant was purified through a Sep-Pak C18 reversal phase column.The radiochemical purity and in vivo stability were determined using silica gel thin layer chromatography (TLC).The biodistribution of 125I-FIAU in Kunming mice was also detected.The results showed that 125I-FIAU could be radiolabeled effectively with FTAU,with mean labeling rate being (81±0.38)％ (n =5).The mean radiochemical purity of (98.01±0.40)％ (n=5) was achieved after a reversal phase Sep-park column purification.125I-FIAU was stable when incubated in normal human serum or in saline at 37℃,with a radiochemical purity ＞96％ during a 0.5-24 h time period.Biological experiments exhibited rapid clearance of 125I-FIAU from the blood pool.125I-FIAU was mostly excreted by kidneys.125I-FIAU in myocardium dropped conspicuously after 8 h and there was hardly retention at 24 h.We were led to concluded that the new method of radioiodinization of FTAU for the preparation of 125I-FIAU is easy,highly effective and stable in vivo.The biodistribution of 125I-FIAU in Kunming mice showed it can serve as an imaging probe for myocardial reporter genes.
ABSTRACT
Summary: In order to investigate the clinical significance of 99mTc-Tetrofosmin (TF) seintigraphy in the evaluation of lung cancer and mediastinal lymphoid node involvement, 33 patients with pulmonary neoplasmas were subjected to both 99mTc-TF scintigraphies and CT scans in one week before their operations or puncturations. All the images were judged visually and the emission images were analyzed with semi-quantitative methods in addition. The results of each group were compared. There was marked difference in target/non-target (T/N) ratio between the lung cancer group and the benign lesion group (P<0.001). Moreover, in the lung cancer group, T/N ratio in tomographies was significantly higher than that in planar images (P<0.01). The sensitivity and accuracy of semi-quantitative analysis in 99mTc-TF SPECT were significantly higher than those of CT in the diagnosis of pulmonary neoplasmas (P<0.05 and P<0.01 respectively), so was the sensitivity of 99mTc-TF SPECT vs CT in the diagnosis of mediastinai lymphoid node metastasis (P<0.05). It was also found that epidermoid squamous cell carcinomas and adenocarcinomas had a higher T/N ratio than in small cell carcinomas (P<0.05), and 2 h washout rate (WR) of adenocarcinomas was higher than that of epidermoid squamous cell carcinomas (P<0.05). In conclusion, 99mTc-TF scintigraphy showed a favorable diagnostic accuracy in appraising lung cancers and mediastinal lymph node metastases. Furthermore semi-quantitative technology can improve the accuracy, and is potential to offer some information about histological type of the cancer tissue. Therefore, 99mTc-TF scintigraphy will be a useful tool in the diagnosis and staging of lung cancer.
ABSTRACT
The 15-mer oligonucleotide sequence was synthesized, aminolinked (sense and antisense phosphodiester) and conjugated with S-Acetyl-NHS-MAG3 by a N-hydroxy-succinimide derivative. The purified MAG3-DNA was radiolabeled with 99mTc by transchelation from sodium tartrate and free 99mTc was separated by gel filtration. The radiolabeled antisense and sense probes were injected intravenously in mammary tumor-bearing KM mice(1×106 cells,6 days post inoculation).Biodistribution was studied and the mice were imaged.Essentially complete conjugation was achieved by reverse-phase Sep-Pak C18 chromatography analysis.The MAG3-DNA was labeled with 99mTc at room temperature and neutral pH, with a mean labeling efficiency of 80.11 percent (s.d=2.96 percent , N=4). After labeling, the stability of the DNA in saline or serum was retained as determined by reverse-phase Sep-Pak C18 chromatography analysis, except a shift at 30 min in serum incubation which might suggest a short time serum protein binding. The labeled antisense DNA still remained the ability to hybridize with its complementary DNA. The pharmacodynamics of 99mTc labeled c-myc probes (antisense and sense) in mammary tumor-bearing KM mice did not change with the time postinjection. The highest accumulation of label was in the liver first, with the kidney and small bowel next. The injected activity localized in the lesion as early as 30min and reached a saturation value at 4hr. The accumulation of radioactivity in the tumor was lower at all time points in animals receiving the blocking oligonucleotides or sense probes. All images obtained with 99mTc-MAG3-c-myc antisense probes showed specific accumulation of radioactivity at the site of tumor. Radiolabel rapidly accumulates at the site of tumor and remains associated with the site even though circulation levels of radioactivity have greatly diminished. The tumor was readily evident since 45min and reached the highest tumor-to-muscle ratio at 4hr. The quite encouraging result was obtained at 20hr to 22hr when the background activity was diminished sufficiently. Positive imaging was not obtained in case of control group (in which non-conjugated, non-labeled antisense oligonucleotides were administered 2hr before the radiolabeled antisense probes were injected) and of sense group. Conclusion The 99mTc labeled antisense probe may provide a sensible and specific tool for noninvasive imaging of c-myc oncogene mRNA for a variety of malignant tumors at an earlier stage