Preparation, biodistribution, and micropet imaging of ⁴⁵Ti‐transferrin

Abstract

Several titanium complexes are currently being investigated for their ability to exhibit antitumor activity both in vitro and in vivo (1). Sun et al. recently showed the first specific Ti(IV)‐protein complex through binding experiments with transferrin (2). This suggests that transferrin could be the mode of transport for titanium anticancer drugs since tumor cells show high levels of transferrin receptors on the cell surface (3). Transferrin has a molecular weight of 80 kDa and is only 30% saturated with iron, leaving available binding sites for other metal ions (4). Titanium‐45 has a half‐life of 3.09 hours and a positron branching ratio of 85% with an Eβ+max of 1.04 MeV. The work of Ishiwata et al. investigated 45Ti as a potential metal for labeling pharmaceuticals for PET imaging (5). In the current study, the biodistribution of 45Ti‐transferrin was examined to investigate the mode of transport of titanium compounds to tumors.

Spatial light modulator based active wide-field illumination for ex vivo and in vivo quantitative NIR FRET imaging

“…Our biodistribution results of FRET NIR pair match previous results [13,[21][22][23][24] suggesting that upon injection of radioactively or fluorophore labeled Tfn into nude mice, and the labeled Tfn can pass freely through various tissues and reach epithelial-and phagocytic-rich organs, such as liver, and spleen and kidney, rapidly. During circulation, the Tfn is potentially taken up by phagocytic cell-rich organs, such as liver and spleen leading to their clearance after phagocytosis from the animal [13,[21][22][23][24]. Although FD% signal at 6hr-post injection is detected mainly in liver, spleen and brain tissues with high Tfn uptake, the FD % signal after 24hr-post injection remains predominantly in the liver indicating the importance of this organ in the metabolism and catabolism of Tfn.…”

“…TfnR is predominantly expressed in liver and it is also expressed in kidney, spleen, brain and very low expression in heart [13,[21][22][23][24]. Thus, the heart is expected to exhibit much less internalization of Tfn than the other four organs.…”

Cyclotron Production of Unconventional Radionuclides for PET Imaging: the Example of Titanium-45 and Its Applications

“…The work also demonstrated a clear spatial resolution observed down to a rod diameter of 1.25 mm using a Derenzo phantom, i.e., a resolution comparable with 18 F, only with a slight degradation due to the higher energy endpoint and consequent range widening of positrons emitted by 45 Ti (see Figure 2) [31]. Another study of Vavere and Welch [32] produced 45 Ti and used small animal imaging with 45 Ti-transferrin, which provided new insights about the mechanism of action of a new class of cytostatic agents based on titanium complexes. This research performed a direct labeling of apotransferrin with 45 Ti and studied the resultant biodistribution.…”

“…This research performed a direct labeling of apotransferrin with 45 Ti and studied the resultant biodistribution. The microPET images provided indications on the increased uptake of 45 Ti-transferrin in tumors, with retention up to 24 h, demonstrating that titanium radiopharmaceuticals could be explored as new tools for the in vivo Another study of Vavere and Welch [32] produced 45 Ti and used small animal imaging with 45 Ti-transferrin, which provided new insights about the mechanism of action of a new class of cytostatic agents based on titanium complexes. This research performed a direct labeling of apotransferrin with 45 Ti and studied the resultant biodistribution.…”

Positron and γ-ray intensities in the decay of 45Ti

“…According to the work of Becker et al [16] metalloproteins are ambitious targets for therapy and diagnosis of tumour growth or neurodegenerative diseases like stroke. In biological studies Vāvere and Welch [17] [19] in 1941, the corresponding -radiation was not discovered till 1960 by Ishii and Takahashi [20]. In 1965 Gföller and Flammersfeld [21] determined the four most intense -rays connected with its decay.…”