The effect of ligand structure on glutathione-mediated decomposition of propylene amine oxime derivatives

99mTc-Labeled Small Peptides as Diagnostic Radiopharmaceuticals

“…Tetradentate ligand PnAO (3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime) was first shown by Troutner and co-workers to react with the [TcO] 3+ core and form a neutral technetium complex [TcO(PnAO)], which demonstrates transient flow-related brain uptake in animal models and in humans . As a result, a large number of PnAO derivatives were synthesized and studied as brain imaging agents. − It has been shown that PnAO technetium-oxo complexes all have a square pyramidal coordination geometry with the two amine N being deprotonated and the two hydroxy groups sharing the same proton via hydrogen bonds. , The PnAO chelating group, an example of which is shown in Figure , has been used for the 99m Tc-labeling of a nitroimidazole, − biotin, and a somatostatin analogue. , The advantage of using PnAO type of BFCAs is that the radiolabeling can be performed at ambient temperature . The disadvantages include low specific activity for the radiolabeled biomolecules, solution instability, and extremely high lipophilicity of the technetium chelate.…”

“…219 As a result, a large number of PnAO derivatives were synthesized and studied as brain imaging agents. [220][221][222][223][224] It has been shown that PnAO technetium-oxo complexes all have a square pyramidal coordination geometry with the two amine N being deprotonated and the two hydroxy groups sharing the same proton via hydrogen bonds. 220,221 The PnAO chelating group, an example of which is shown in Figure 11, has been used for the 99m Tclabeling of a nitroimidazole, [225][226][227] biotin, 228 and a somatostatin analogue.…”

Powder X-ray studies ofmeso-hexamethyl propylene amine oxime (meso-HMPAO) in two different phases

“…It is well known that both diastereomeric forms of hexamethyl propylene amine oxime, meso-HMPAO, (I), and d,l-HMPAO, (II), have important radiopharmaceutical applications in nuclear medicine after labelling with 99m Tc (Neirinckx et al, 1987;Sasaki & Senda, 1997;Roth et al, 1992;Jurisson et al, 1986). For example, 99m Tc-d,l-HMPAO has been widely used as a leukocyte labelling agent and for SPECT (single photon emission computed tomography) imaging of regional cerebral blood perfusion (Jurisson et al, 1986).…”

The Design and Properties of 99mTc Chelates for Brain Perfusion Imaging

“…No unique ''""Tc product results from the in vivo dissociation of this chelate and the chemical reactions responsible for these processes is not fully understood. Neirinckx et al [23] suggests that intracellular reduced glutathione (GSH) plays a major role in triggering dissociation of ^^'"Tc-djl-HMPAO, however, other reactions must also be considered [24]. Regardless of the chemical or biochemical reactions involved, once the non-diffusible '^'"Tc products are formed inside of the cells (e.g., small charged ^'•"Tc species or ^^"•Tc bound to intracellular proteins or structures), the retention of ^^^Tc activity in brain is prolonged.…”