Studies On Distribution And Imaging Of ⁶⁸Ga-labelled DOTA-cRGD Peptide In Mice Bearing Tumors

Objective:1. To explore the 68 Ga labelling method and quality monitoring of DOTA-c RGD.2. To explore the biodistribution and pharmacokinetics of 68Ga-DOTA-c RGD in healthy ICR mice.3. To explore the micro PET imaging effect of 68Ga-DOTA-c RGD in A549 human lung adenocarcinoma models. Methods:1. The αvβ3 expression in A549 cancer tissues was estimated respectively by flow cytometry and immunohistochemistry.2. 68Ga-DOTA-c RGD was synthesized through water bath at PH=5.0 while HEPES as buffer system. The radiolabeled yield and stability was analysed with HPLC.3. Biodistribution study was performed following an i.v.injection(given via the tail vein) of 68Ga-DOTA-c RGD. Healthy ICR mice were sacrificed with cervical dislocation at designated time points in group. The blood and major organs were removed, weighed and counted in a gamma scintillation counter to determine the %ID/g(percentage of injected dose related to the organ weight) for each radioactive substance.4. 68Ga-DOTA-c RGD was injected into nude mice beating human lung cancer A549 tumors via tail vain.Dynamic and static images were performed using micro PET.ROI was drawn to calculate the T/NT. Results:1. The quality monitoring and stability 68Ga-DOTA-c RGD. The results of HPLC showed the labelling rate of was(97.8±0.1)%(n=10) and the radiochemical purity was 95% after 2h.2. The biodistribution in normal mice showed rapid clearence from blood(the uptake was(0.10±0.02) %ID/g at 1h postinjection). 68Ga-DOTA-c RGD was excreted mainly via the kidney with little radioactivity accumulation in the liver and gastrointestinal tract(the uptake of liver, stomach, intestine was(0.19±0.13),(0.16±0.06),(0.06±0.01)% ID/g at 1h postinjection).3. The micro PET imaging effect of 68Ga-DOTA-c RGD in A549 human lung adenocarcinoma models.Marked uptake of radioactivity was found in tumor tissue of the Balb/c nude mice bearing human lung cancer with maximum T/NT ratio of 5.93±0.43(n=3) at 1h postinjection.4. 68Ga-DOTA-c RGD could be specifically uptaken by A549 cells with high affinity.5. The αvβ3 expressed in A549 cells and xenograft tissues were(80.65±2.75)%(n=3). Conclusion:68Ga-DOTA-c RGD was easily prepared with high radiolabeling yeild and radiochemical purity. The stability and good biodistribution characteristics make it useful for the diagnosis of human lung cancer with over-expression of the αvβ3 receptor.