The Correlation Between Integrin α_vβ₃ Expression And ^99mTc-3PRGD₂ Imaging In Different Pathological Grades Of Brain Glioma

Objective:(1) to find out the the biological distribution and optimal time for imaging of 99mTc-3PRGD2 in brain glioma, to explore the correlation between different pathlogical grade with 99mTc-3PRGD2. (2) to find out the correlation betweenαvβ3 expression and 99mTc-3PRGD2 imaging in different pathological grades of brain glioma,to explore the mapping mechanism.Methods:23 brain glioma patient underwent dynamic imaging in 10 min,2 h,4 h and brain SPECT/CT in 2 h,4 h after injection of 99mTc-3PRGD2. Regions of interest (ROIs),2 cm, were placed over major organs (heart.lung, liver, spleen, kindney, muscle). The location of the ROIs was then copied to other place of the organ and count. Polygonal ROIs adapted to the contour of bladder and intestin with the maximum activity were drawn. Then each count divide the total counts of the whole body in 10 min,2 h and 4 h. Results are expressed in ID%. In the brain SPECT/CT scans, ROIs were set 1 cm in tumor and normal tissue and ratios of tumor-to-normal were caculated. All the patient have a surgery in 1 week. The samples were sent to pathological examination with hematoxylin and eosin stain and immuohistochemistry. All the patient classify into low malignant group and high malignant group according hematoxylin and eosin stain.αvβ3 expression was positive when it show brown particles in cell and vascular. Then, all the patient were divided into different group accordingαvβ3 expression:non-expression.high expression, moderate expression and low expression.Result:99mTc-3PRGD2 shows rapid renal excretion and clearance from the blood pool, with blood-pool activity 44.1%,27.4%,17.0%,14.2% and 11.4% after injection 10 min,20 min,30 min,45 min,60 min。The highest ID% in organs in 10 min, 2 h, 4 h after injection were found in baldder (14.07±3.41)%ID, (3.19±1.39)%ID,(1.73±0.89)%ID, followed by the kidneys(10.87±1.81)%ID). (6.11±1.43)%ID,(7.01±2.53)%ID. In the liver, there is some retention of activity over time. At the same time, low activity can be seen in biliary and gut. The dynamic scans revealed 99mTc-3PRGD2 was mainlv eliminated from urinary svstem. In the SPECT/CT scans, 13 out of 23 patient showed 99mTc-3PRGD2 uptake in tumor at 2 h, while rapid tracer accumulation were seen at choroid plexus, parotid gland and thyroid gland. At 4 h, tumor showed perfect with the activity decrease in these glands.99mTc-3PRGD2 uptake cannot be seen in other patient.There are 13 high malignant patient and 10 low malignant patient according hematoxylin and eosin stain.10 high malignant and 3 low malignant patient show 99mTc-3PRGD2 positive imaging. There are significant difference between HM and LM(X2=5.064,P=0.04.P<0.05). At the same time, ratios of tumor-to-tumor tissue(T/NT) was 1.87±0.36,1.94±0.40 in HM and 1.42±0.18,1.46±0.26 in LM at 2h and 4 h respectively. There are significant difference between HM and LM (P2 h=0.002,P<0.05;P4 h=0.003,P<0.05). Moreover, the malignancy of the tumor was related with the uptake of T/NT ratio (r2 h=0.622.P=0.002,P<0.05;r4 h=0.593.P=0.003,P<0.05).αvβ3, brown particles,was mainly expressed in membrane.invasive edge or vascular endothelial, but seldom in central necrosis and surrounding normal tissue.1 patient show low expression,4 patient show moderate expression and 8 patient show high expression in high malignant group. At the same time,4 patients show moderate expression and 6 patient show low expression in low malignant group. There are significant difference between HM and LM(X2=11.374.P=0.003,P<0.05).7 patients show high expression and 6 show moderate expression in 13 patients who show 99mTc-3PRGD2 positive imaging.1 patients show high expression,3 show moderate expression and 6 patients show low expression in 10 patients, who show negative imaging.There are significant difference in 99mTc-3PRGD2 imaging between high expression, moderate expression and low expression(P=0.000,P<0.05).αvβ3 expression was related with with the uptake of 99mTc-3PRGD2 (r2h=0.419, P=0.047,P<0.05;r4h=0.422,P=0.045,P<0.05).Conclution:(1)99mTc-3PRGD2, mainly eliminated from urinary.shows rapid renal excretion and clearance from the blood pool, can used in clinical image.(2) 99mTc-3PRGD2 may be a good tracker in tumor imaging in most regions of the body except for the urogenital tract, the spleen and liver.(3) We recommend imaging 4 h after injection of the tracer for optimal lesion-to-background contrast. (4) 99mTc-3PRGD2 imaging correlated to the malignancy of brain glioma and maybe severed to evaluate the malignant degree before surgery.(5)The expression ofαvβ3 in brain glioma show related to the malignancy. (6) 99mTc-3PRGD2 imaging may serve as an important non-invasive method in predicting the avP3 expression.