Hydrophilic 99mTc-EC and nonlipophilic 99mTc- MAMA′-BA complexes, owing to the existing of intact blood-brain barrier (BBB) in vivo, cannot cross from blood to brain. Previous studies showed that insulin is selectively transported by receptor-mediated transcytosis through the brain capillary endothelial wall that makes up the BBB. In this paper, based on the characteristic of the insulin receptor enriched in brain capillary, the complexes of hydrophilic 99mTc-EC and nonlipophilic 99mTc-MAMA′-BA are conju- gated to insulin respectively. After purification, the radio- chemical purity of 99mTc-EC-insulin and 99mTc-MAMA′- BA-insulin was > 90% and the stability in vitro was good. Expectation for the special formulation can be internalized and endocytosed into the capillary membrane by the vec- tor-mediated brain delivery system, and transported 99mTc-labeled conjugate through the BBB in vivo, thus en- hancing brain uptake in mice. The biodistribution results of 99mTc-EC-insulin and 99mTc-MAMA′-BA-insulin in mice in- dicated that the brain uptake was higher than 99mTc-EC and 99mTc-MAMA′-BA to some extent. The ratios of brain uptake of 99mTc-EC-insulin to 99mTc-EC, 99mTc-MAMA′-BA-insulin to 99mTc-MAMA′-BA were 4―6 at 2 and 3 h post-injection respectively. In conclusion, the given results have illustrated a new way of brain uptake enhancing for nonlipophilic like complexes that have BBB delivery problems. It has a poten- tial value for the ongoing development of 99mTc-labeled ra- diopharmaceuticals for CNS receptors imaging. Hydrophilic 99mTc-EC and nonlipophilic 99mTc-MAMA’-BA complexes, owing to the existing of intact blood-brain barrier (BBB) ​​in vivo, can not cross from blood to brain. Previous studies showed that insulin is selectively transported by receptor-mediated transcytosis through this brain capillary endothelial wall that makes up the BBB. In this paper, based on the characteristic of the insulin receptor enriched in brain capillary, the complexes of hydrophilic 99mTc-EC and nonlipophilic 99mTc-MAMA’-BA are conjuged to insulin respectively. After purification, the radio-chemical purity of 99mTc-EC-insulin and 99mTc-MAMA’-BA-insulin was> 90% and the stability in vitro was good. Expectation for the special formulation can be internalized and endocytosed into the capillary membrane by the vec- tor-mediated brain delivery system, and 99mTc-labeled conjugate through the BBB in vivo, thus en hancing brain uptake in mice. The biodistribution results of 99mTc-EC-insulin and 99 mTc-MAMA’-BA-insulin in mice in- dicated that the brain uptake was higher than 99mTc-EC and 99mTc-MAMA’-BA to some extent. The ratios of brain uptake of 99mTc- EC-insulin to 99mTc- 99mTc-MAMA’-BA-insulin to 99mTc-MAMA’-BA were 4-6 at 2 and 3 h post-injection respectively. In conclusion, the given results have illustrated a new way of brain uptake enhancing for nonlipophilic like complexes that have BBB delivery problems. It has a poten- tial value for the ongoing development of 99mTc-labeled ra- diopharmaceuticals for CNS receptors imaging.