Objective  To explore how to label small molecule inhibitor K237 (HTMYYHHYQHHL) of vascular endothelial growth factor receptor-2

(VEGFR-2

KDR) with technetium 99m and to study pharmacokinetic characteristics and body distribution of the labeled peptide in healthy animals.   Methods  MAG3-K237 was prepared through chemosynthesis

and then labeled it with

99

Tc

m

. Then its stability and physicochemical properties were determined by paper chromatography. The best compartment model and its pharmacokinetic parameters were obtained through determining blood radioactive concentrations at 1.5

3

5

10

30

60

90

120

240 and 480 min after injection of 37 MBq

99

Tc

m

-MAG

3

-K237 into 6 rabbits. SPECT imaging was applied to investigate the dynamic distribution of the peptide in rabbits. After 7.4 MBq

99

Tc

m

-MAG

3

-K237 injected into 35 healthy mice via caudal vein

the mice were sacrificed in 1

5

10

30

60

120 and 240 min respectively after the injection (n=5 at each time point)

and then their samples of blood

heart

lungs

liver

spleen

intestine

muscle

bone and brain were collected to measure the weight and radioactive counting of each organ after injection

and to calculate %ID/g of each organ.   Results  The radiochemical purity of

99

Tc

m

-MAG

3

-K237 was (97.98±0.76)%

which was (96.15±0.37)% after 8 h being conserved under room temperature (25℃) and the cysteine replacement rate was from 0.2% to 0.37% and the labeled peptide could not combine with blood serum protein. Its dynamics in rabbits conformed to the three-compartment model with the weight of 1/c

2

and the main parameter were as follows: t

1/2α

t

1/2β

and t

1/2γ

were 4.00±3.53

24.48±9.84  and 852.24±444.00 min respectively; CL was 1.833±0.408 ml/min. SPECT imaging and distribution test in mice showed that the peptide could be quickly cleared from blood in healthy animals and distributed more in the kidney

liver and intestine

but its distribution in the liver became fewer in 30 min after injection.   Conclusion  We obtaine

d the

99

Tc

m

labeled peptide with high radiochemical purity (95%) and perfect stability

which could be quickly cleared from blood and excreted though liver and kidney.