Synthesis, radiolabeling and biological evaluation of propylene amine oxime complexes containing nitrotriazoles as hypoxia markers.

Two propylene amine oxime (PnAO) complexes, 1, containing a 3-nitro-1,2,4-triazole and 2, containing two 3-nitro-1,2,4-triazoles, were synthesized and radiolabeled with (99m)Tc in high labeling yields. Cellular uptakes of (99m)Tc-1 and (99m)Tc-2 were tested using a S180 cells line. Under anoxic conditions, the cellular uptakes of (99m)Tc-1 and (99m)Tc-2 were 33.7 ± 0.2% and 35.0 ± 0.7% at 4 h, whereas the normoxic uptakes of the two complexes were 6.0 ± 1.6% and 4.6 ± 0.9%, respectively. Both (99m)Tc-1 and (99m)Tc-2 displayed significant anoxic/normoxic differentials. The cellular uptakes were highly dependent on oxygen and temperature. Biodistribution studies revealed that both (99m)Tc-1 and (99m)Tc-2 showed a selective localization in tumor and slow clearance from it. At 4 h, the tumor-to-muscle ratios (T/M) were 3.79 for (99m)Tc-1 and 4.58 for (99m)Tc-2. These results suggested that (99m)Tc-labeled PnAO complexes (99m)Tc-1 and (99m)Tc-2 might serve as novel hypoxia markers. By introducing a second nitrotriazole redox center, the hypoxic accumulation of the marker was slightly enhanced.

Synthesis of Tc-D,D-HMPAO and Tc-L,L-HMPAO and their comparison of chemical and biological properties.

Tc-D,D- and TC-L,L-HMPAO were synthesized. The stability of Tc-D,D- and TC-L,L-HMPAO in vitro is similar to that of d,l-isomers by the spectrophotometric and three strips methods. Cerebral uptake (%D in brain) for the L,L-isomer is higer than the D,D- and d,l-isomer in rats. Delayed studies shows that T-L,L-HMPAO reveals less washout and reflects a higher cerebral deposition properties than the D,D- and d,l-isomer.

Preparation and properties of 99Tcm-exametazime using stannous ion augmentation of fractionated cold kits.

Fractionation of 99Tcm-exametazime enables several patients doses to be prepared from one vial. To overcome the disadvantages of storage at -70 degrees C, storage at higher temperatures was investigated with replacement of stannous ions before use. Kits were fractionated using a nitrogen-purged 0.9% w/v sodium chloride injection, sub-dispensed into five nitrogen-filled vials in an aseptic environment and stored at -20 degrees C. Under these conditions, exametazime vials failed quality control in approximately 1 week. However, the addition of stannous pyrophosphate solution (10 micrograms Sn(II) in 0.1 ml, prepared by aseptic dilution of a red blood cell labelling kit) immediately before 99Tcm-pertechnetate produced 90.1 +/- 1.6% (n = 8) lipophilic complex with a normal rate of decomposition. Biodistribution studies of this product in mice compared with the full kit showed identical brain and other organ uptakes. This product was used for cerebral imaging in patients with 90.5 +/- 3.3% lipophilic complex (n = 647) at approximately 3 min and produced excellent clinical results. It is concluded that stannous ion augmentation ('reboot') using approved Sn(II)-pyrophosphate kits is a viable option for institutions with facilities for aseptic preparation of fractionated exametazime kits, enabling substantial cost savings. Other advantages include removal of restrictions on generator eluate and 'rejuvenation' of expired kits.