ABSTRACT
Objective To study the tumor targeting ability and application of farnesylthiosalicylic Acid (FTS) and heptamethine carbocyanine fluorescent dye-mediated near-infrared imagine in living animals, and confirm the inhibitory effect of this compound on growth of tumor cells.Methods Human breast cancer cell line MCF-7, glioma cell line U251 and prostate cancer cell line PC3 were cultured to logarithmic growth phase, and different concentrations of FTS and FTS-IR783 were added, respectively.We observed the inhibitory effect of those two compounds on the growth of tumor cells.Under fluorescence microscopy, specific accumulation of FTS-IR783 in these tumor cells was observed.The tumor cells (1×106) were transplanted subcutaneously into nude mice.These mice were subjected to intraperitoneal injection of FTS-IR783 (10 nmol/mouse) two weeks later.In the in vivo imaging, near infrared fluorescence signal and tumor volume were measured and their correlation was analyzed.Results Compared with FTS, FTS-IR783 significantly inhibited the growth of MCF-7, U251 and PC3 cells in vitro.FTS-IR783 was specifically uptaken by these three kinds of tumor cells, showing strong near infrared fluorescence in cell agglomerates.After subcutaneous injection of FTS-IR783, the correlation between fluorescence intensity and tumor volume was 0.987, 0.998 and 0.971, respectively.Conclusions The compound of FTS conjugated with near infrared fluorescent dye IR-783 can specifically recognize tumor cells, in both in vitro and in vivo imaging.At the same time, the compound can significantly inhibit the growth of tumor cells, and may be expected to become a new potential targeted drug.
ABSTRACT
Objective To establish a mouse model of early lung adenocarcinoma to serve the imaging studies of early lung adenocarcinoma .Methods Two-hundred and ten 4-week old SPF female Kunming mice were randomly divided into 5 experimental groups (40 mice per group) and 1 control group (10 mice).The mice of experimental groups were subcutaneously injected with a dose of 0.2 ml 1-methyl-3-nitro-1-nitroso-guanidine ( MNNG) solution in concentration of 2.0 mg/mL weekly for 1, 2, 4, 8, 12 weeks (group A-E), respectively, while the mice of control group was subcutane-ously injected with 0.2 mL saline weekly for 12 weeks.Ten mice were randomly sacrificed from each experimental group at the 60th, 80th, 100th and 120th days after initial injection ( group A60 , group A80 , group A100 , group A120; group B60 ,……and so on) , and the bilateral lungs were dissected .The tumor occurrence rate , number and size of lung tumors were observedandrecorded.Results 1.Thetumoroccurrencerateandnumberoflungtumorswerepositivelyproportionalto the time and dose of MNNG injection .No tumor was found in any group at the 60th day.2.At the 80th day, the tumor oc-currence rate in the groups A, B, C, D and E was 0, 10%, 30%, 40%and 50%, respectively.The number of tumors in each group was 0, 4, 42, 60 and 81, respectively.The number of tumors smaller than 0.5 mm in diameter was 0, 4, 25, 31 and 40, respectively.3.At the 100th day, the tumor occurrence rate was 20%, 40%, 100%, 100%and 100%, re-spectively.The number of tumors was 6, 19, 187, 223 and 301, respectively, and the number of tumors smaller than 0.5 mm in diameter was 5, 16, 132, 124 and 123, respectively.4.At the 120th day, the tumor occurrence rate was 30%, 50%, 100%, 100%and 100%, respectively.The number of tumors was 30, 124, 302, 351 and 362 per group, respec-tively.The number of tumors smaller than 0.5 mm in diameter was 21, 98, 123, 140 and 108, respectively.The induced lung adenocarcinomas were confirmed by pathology .Conclusions MNNG solution 0.2 mL (2.0 mg/mL) subcutaneously injected weekly for 4 weeks can produce 100%occurrence rate of lung adenocarcinoma in mice and most tumors are smaller than 0.5 mm in diameter at 100th day after initial injection .It is a most suitable model for imaging studies of mouse early lung adenocarcinoma .