The Experimental Study On Labeling Method Of A Low Dosage Of Octreotide With Rhenium-188 And Its Biodistribution In Normal Mice And Nude Mice

Objective To study a method for labeling a low dosage of octreotide with rhenium-188 and building a nude mice mode which bearing H460 none small cell lung cancer. To study the biodistribution of ¹⁸⁸Re-octreotide in normal mice and nude mice. Methods The amount of stannous chloride changed from 50 to 1600μg, octreotide was 10,20 or 30μg, pH value of acetate buffer from 4.0 to 6.0, the volume of rhenium-188 perrhenate from 0.05 to 0.20ml, the reaction temperature from room temperature to 100℃. The labeling efficiency and the in vitro stability of ¹⁸⁸Re-octreotide were analyzed.Those normal mice were been killed and the blood,major organs were taken out from those mice at 0.5h, 1h, 2h, 4h, 24h after been injected ¹⁸⁸Re-octreotide through the tail veins, and one normal mouse have been randomized allocated from each term for SPECT scanning before those mouse were killed, then the radioactivity count of those organs were measured. Similarly,four nude mice had SPECT scaned at 2h, 4h, 24h,48h after injection, and using ROI technique for semi-quantitative analysis of main organ and tumor uptake. Others nude mice were killed at 2h, 4h, 24h,48h after injection,then tumors and major organs were taken out and the radioactivity count of those organs and tumors were measured. Two nude mice SPECT scaned after intratumor injected ¹⁸⁸Re-octreotide and the tumor/organ ratios were studied. Results The optimal conditions for rhenium-188 labeling reaction are follows: 0.1ml sodium glucoheptonate(0.3mmol/L),0.05ml stannous chloride(16g/L)was dissolved by 0.1mol/ L hydrochloric ,0.1ml acetate buffer (pH=5)and 0.1ml octreotide (0.1g/L)were mixed at room temperature for 1h with nitrogen atmosphere and continuous agitating. 0.1ml fresh rhenium-188 perrhenate was added, water bathing 100℃for 30min. It was found that the labeling efficiency of ¹⁸⁸Re-octreotide was (95.3±1.8)%, after it was cooled in room temperature, radiochemical purity was (89.6±2.5)% at 24h. ¹⁸⁸Re- octreotide was major distributed in lives, small bowels, large bowels and kidneys in normal mice, and major distributed in tumors,lives, small bowels, large bowels and kidneys in nude mice.The largest uptake of tumors is 9.8%ID/g at 4h after injection.The largest tumor/muscle ratios in the SPECT study in those nude mice is 7.1 at 24h after injection. Those nude mice of intratumor injected have higher tumor/organ ratios than tail vein injected ones. Conclusion This method of labeling octreotide with rhenium-188 is convenient with satisfactory in vitro stability and labeling efficiency, and does not need further purification to the labeling radiopharmaceutical before administration. The distribution of radionuclide will been reduced in the non-target organs because of the low dosage of octreotide. The clear of ¹⁸⁸Re-octreotide from blood is fast, ¹⁸⁸Re-octreotide was up taken highly by small and large bowels followed by kidneys and livers. the tumor/muscle ratios in nude mice is large enough for targeting therapy. The tumor/organ ratios have been raised through intratumor injected.