Synthesis, radiolabeling and biological evaluation of [99m]Tc-labeled deoxyglucose derivatives for molecular imaging

Two deoxyglucose [DG] derivatives, [alpha, beta]-2-deoxy-2-amino[ethylcarbamate]-D-glucose [ECB-DG] and [alpha, beta]-2-deoxy-2-amino[1,2-dihydroxypropyl]-D-glucose [DHP-DG], were synthesized and radiolabeled successfully with [[99m]Tc[H[2]O][3][CO][3]][+] complex. [[99m]Tc]-ECB-DG and [[99m]Tc]-DHP-DG complexes were prepared [96% and 93% radiochemical purities respectively] by using 46 mCi of Na[99m]TcO[4] in 1 mL saline. Radio-HPLC analysis of [[99m]Tc]-ECB-DG at pH = 7.4, revealed that labeling with [99m]Tc leads to formation of one radiochemical species with t[R] = 381 second. Three radiochemical species, Na[99m]TcO[4], [[99m]Tc]-DHP-DG and [[99m]Tc[H[2]O][3][CO][3]][+] complexes with t[R] = 342 sec, t[R]= 567 sec and t[R] = 1586 sec respectively, were obtained when [[99m]Tc]-DHP-DG complex evaluated by HPLC. Biodistribution of two complexes were studied on normal mice at 10, 30 and 60 min post-injections. Compared to the [18]F-FDG, [[99m]Tc]-ECB-DG displayed a 2.8-fold reduction in brain uptake [1.7 +/- 0.2 versus 0.61% +/- 0.09], whereas [[99m]Tc]-DHP-DG just showed 1.9-fold reduction in heart uptake [2.2 +/- 0.05towards 1.16 +/- 0.10] at 1 h post-injection.On the basis of our results, it seems that ECB-DG and DHP-DG analogues could be used as brain and heart imaging agent respectively

improved synthesis and preliminary biodistribution study of a technetium-99m-labeled 2-amino-2-deoxy[thioacetyl]-D-glucose complex [[99mTc]-TA-DG] as a tumor imaging agent

This report describes the synthesis of 2-Amino-2-deoxy[S-benzoylthioacetyl]-D-glucose [S-Bz-TA-DG], radiolabeled with [99mTc[CO]3[OH2]3]+complex with a procedure including deprotection of the benzoyl group, characterization by HPLC using a C18 reverse phase column and preliminary biodistribution study in normal mice. [99mTc[CO]3[H2O]3]+complex was used to label TA-DG with 99mTc. This complex was prepared using up to 46 mCi of Na99mTcO4 in 1mL saline. The radiochemical purity [>95%] was determined by TLC in normal saline solution as the mobile phase. Radio-HPLC analysis of [99mTc]-[TA-DG] at pH=9.5-10, revealed that labeling with 99mTc resulted in the formation of three radiochemical species [Na99mTcO4 with tR=5.7 min, [99mTc[CO]3[H2O]3]+complex with tR=27.5 min and [99mTc]-[TA-DG] [yield>85%] with tR=8.2 min] with different HPLC-profiles. The biodistribution of the [99mTc]-[TA-DG] complex was studied in normal mice [body mass 25-35 g] at 30 min and 1 h post-injection, according to a published procedure. This complex showed negligible brain uptake [0.13% +/- 0.03 ID] at 30 min post-injection, an efficient clearance from the blood, a rapid excretion to the urine and a low retention in the liver and kidneys. Nonfunctionalized carbohydrate compounds such as glucose are generally weak ligands for chelating with 99mTc. Therefore, functionalization with an external chelating group or the insertion of some functional groups is essential to obtain strong metal-binding compounds. On the basis of our results, it seems that [99mTc]-[TA-DG] has not most of the favorable properties as an imaging agent for brain tumors