Serial stimulated thyroglobulin measurements are more specific for detecting distant metastatic differentiated thyroid cancer before radioiodine therapy

Objective: Preablative stimulated thyroglobulin (ps-Tg) has the potential to be used in identifying distant metastatic differentiated thyroid carcinoma (DM-DTC), but its single level can be affected by remnant thyroid tissue and thyrotropin (TSH). The objective of this retrospective study was to evaluate the value of serial ps-Tg measurements in identifying DM-DTC specifically. Methods: A total of 317 DTC patients with serial measurements of ps-Tg, TSH and anti-Tg antibody were divided into M1 (n=72) and M0 (n=245) according to the presence of distant metastasis (DM) or not. The initial psTg measurement, with a corresponding TSH exceeding 30 mu IU/mL, was marked as Tg1, and ps-Tg measured right before radioactive iodine (RAI) therapy was defined as Tg2, with a median interval of 8 days. Delta Tg denotes Tg2-Tg1, and Delta TSH denotes TSH2-TSH1. Tg1, Tg2, Delta Tg, and Delta Tg/Delta TSH were tested for efficacy in identifying DM-DTC using receiver operating characteristic (ROC) curve analysis, and further compared with chest computed tomography (CT) and posttreatment whole-body RAI scan (RxWBS). Results: Compared with single ps-Tg measurement (Tg1 or Tg2), both Delta Tg and Delta Tg/Delta TSH were more narrowly distributed around zero in the M0 group, which made their distribution in the M1 group more distinguished in a relatively dispersed way. Delta Tg/Delta TSH manifested a higher accuracy (88.64%) and specificity (90.20%) in identifying DM-DTC than Tg1 or Tg2 measurements, with a much higher specificity than chest CT (90.20% vs. 66.00%) and a much higher sensitivity than RxWBS (83.33% vs. 61.11%). Conclusions: Serial ps-Tg measurements even over as short an interval as 8 days hold incremental value in identifying DM-DTC. Delta Tg/Delta TSH is a specific early biochemical marker for DM-DTC.

Baculovirus vector-mediated transfer of NIS gene into colon tumor cells for radionuclide therapy

AIM:To investigate the feasibility of radionuclide therapy of colon tumor cells by baculovirus vector-mediated transfer of the sodium/iodide symporter(NIS) gene.METHODS:A recombinant baculovirus plasmid carrying the NIS gene was constructed,and the viruses(BacNIS) were prepared using the Bac-to-Bac system.The infection efficiency in the colon cancer cell line SW1116 of a green fluorescent protein(GFP) expressing baculovirus(Bac-GFP) at different multiplicities of infection(MOI) with various concentrations of sodium butyrate was determined by flow cytometry.An in vitro cytotoxicity assay was also conducted after infection of SW1116 cells with Bac-NIS.Iodine uptake of Bac-NIS infected SW1116 cells and inhibition of this uptake by sodium perchlorate was examined,and the effect of Bac-NISmediated 131 I in killing tumor cells was evaluated by cell colony formation tests.RESULTS:Infection and transgene expression in SW1116with Bac-GFP were significantly enhanced by sodium butyrate,as up to 72% of SW1116 cells were infected with the virus at MOI of 400 and sodium butyrate at 0.5 mmol/L.No obvious cytotoxicity was observed under these conditions.Infection of SW1116 with Bac-NIS allowed uptake of 131 I in these tumor cells,which could be inhibited by sodium perchlorate.The viability of SW1116 cells infected with Bac-NIS was significantly lower than with Bac-GFP,suggesting that NIS gene-mediated 131 I uptake could specifically kill tumor cells.CONCLUSION:Baculovirus vector-mediated NIS gene therapy is a potential approach for treatment of colon cancer.

Fractionated radioimmunotherapy using low doses of iodine 131 labeled anti-CEA monoclonal antibody after tumor volume reduction

OBJECTIVE: To assess the efficacy of fractionated administration of radiolabeled monoclonal antibody in the treatment of metastases after tumor volume reduction surgery, various experimental therapies were studied comparatively. METHODS: A total of 200 inbred mice received tumor implantation from a murine adenocarcinoma cell line. The mice were randomly grouped to give saline, Arc-a, 131I-C50 in single or fractionated doses, cold C50, or non-specific 131I-IgG with or without surgical removal of the implanted tumor xenograft. RESULTS: In comparison to controls, animals receiving Arc-a and radioactive agents had longer survival, smaller tumor, better clinical condition, and less metastases foci. The best therapeutic response was noted after fractionated doses of 131I-C50, which showed better results in every aspect than those treated with other modalities. The favorable outcome was even more pronounced after tumor volume reduction. CONCLUSIONS: Fractionated dosing may improve the deposition of radiolabeled monoclonal antibody (McAb) and provide the best therapeutic effect on implanted tumor and metastases. Thus fractionated radioimmunotherapy (RIT) after tumor volume reduction might be a practical method with promising therapeutic results.

Clinical study of 312 cases with matastatic differentiated thyroid cancer treated with large doses of ^(131)I

Patients with metastatic thyroid cancer (MTC) was routinely treated with a small dose of ^(131)I before 1989. After that we have been switched to multiple courses of large dose ^(131)I therapy. In this paper, the therapeutic result and its effect, in particular on bone marrow depression, pulmonary, parathyroid and salivary gland function as well as chromosome aberration^(1-3) were observed and reported.

Adenovirus-mediated and tumor-specific transgene expression of the sodium-iodide symporter from the human telomerase reverse transcriptase promoter enhances killing of lung cancer cell line in vitro

Background The sodium-iodide symporter （NIS） protein can mediate the active radioiodine uptake.The human telomerase reverse transcriptase （hTERT） promoter is known to be selectively reactivated in majority of tumors and hence could be used for tumor targeting.We constructed a recombinant adenovirus containing the human sodium iodide symporter （hNIS） gene directed by the hTERT promoter, characterized the ability of infected cells in uptaking iodide, and explored the therapeutic efficacy of 131I in a lung cancer cell line in vitro.Methods The hTERT promoter was amplified by PCR from DNA isolated from log-phase HepG2 cells, subcloned into lineralized FL＊-hNIS/pcDNA3, and then the hTERT-hNIS sequence was subcloned into the shuttle plasmid pAdTrack.The recombinant adenovirus Ad-hTERT-hNIS was constructed by AdEasy system.A positive control adenovirusAd-CMV-hNIS and a negative control adenovirus Ad-CMV were created similarly.A549 cells were transduced with recombinant adenoviruses.125I uptake studies and sodium perchlorate suppression studies were used to confirm hNIS expression and function.Toxic effects of 131I on tumor cells were studied by in vitro clonogenic assay.Results We first successfully constructed an adenovirus mediated transgene expression system of the hNIS under the control of hTERT promoter.When infected with recombinant adenovirus constructs expressing hNIS directed by hTERTand CMV-promoters （Ad-hTERT-hNIS and Ad-CMV-hNIS, respectively）, the lung cancer cell line A549 had increased ability to uptake radioiodide up to 23- and 30- fold compared to the control parental cells, respectively.The radioiodide uptake ability of both the Ad-CMV-hNIS and Ad-hTERT-hNIS transduced cell lines were repressed 11-fold by sodium perchlorate （NaCIO4）.The subsequent in vitro clonogenic assay of the infected A549 cell line was further repressed to 23% （Ad-CMV-hNIS） and 30% （Ad-hTERT-hNIS） of the control group after receiving radioiodide for 7 hours （P 〈0.001）.Conclusion Our preliminary study indicates that an adenovirus mediated transgene expression system of the hNIS under the control of hTERT promoter has the potential to become an effective wide-spectrum yet highly specific anti-cancer strategy.

Inhibition of human prostate cancer xenograft growth by 125I labeled triple-helin forming oligonucleotide directed against androgen receptor

Background The failure of hormone treatment for advanced prostate cancer might be related to aberrant activation of the androgen receptor. We have shown that 125I labeled triple-helix forming oligonucleotide （TFO） against the androgen receptor gene inhibits androgen receptor expression and cell proliferation of LNCaP prostate cancer cells in vitro. This study aimed at exploring the effects of the 125I-TFO on prostate tumor growth in vivo using a nude mouse xenograft model. Methods TFO was labeled with 125I by the iodogen method. Thirty-two nude mice bearing LNCaP xenograft tumors were randomized into 4 groups and were intratumorally injected with 125I-TFO, unlabeled TFO, Na125I and normal saline. Tumor size was measured weekly. The tumor growth inhibition rate （RI） was calculated by measurement of tumor weight. The expression of the androgen receptor gene was performed by RT-PCR and immunohistochemical study. The prostate specific antigen （PSA） serum levels were measured by enzyme linked immunosorbent assay. The tumor cell apoptosis index （AI） was detected by TUNEL assay. Results Tumor measurements showed that tumor development was significantly inhibited by either 125I-TFO or TFO, with tumor RIs of 50.79% and 32.80% respectively. 125I-TFO caused greater inhibition of androgen receptor expression and higher AIs in tumor tissue than TFO. Both the tumor weight and the PSA serum levels in 125I-TFO treated mice （（0.93±0.15） g and （17.43±1.85） ng/ml, respectively） were significantly lower than those （（1.27±0.21） g and （28.25±3.41） ng/ml, respectively） in TFO treated mice （all P〈0.05）. Na 125I did not significantly affect tumor growth and androgen receptor expression in tumor tissue. Conclusions The 125I-TFO can effectively inhibit androgen receptor expression and tumor growth of human prostate cancer xenografts in vivo. The inhibitory efficacy of 125I-TFO is more potent than that of TFO, providing a reference for future studies of antigen radiotherapy.