Imaging studies, radiolabeled

There are a variety of interesting studies that successfully used B12 derivatives for selective targeting of tumor cells. In vitro, tumor cells have been specifically killed by cytotoxic B12 derivatives, involving a TC- and CD320-dependent uptake mechanism. In preclinical in vivo studies, radiolabeled or fluorescent B12 derivatives have been shown to accumulate in tumors. Consequently, tumors could be imaged in patients with an "Tn-labeled B12 derivative. However, the high uptake of B12 derivatives in healthy tissue poses a challenge for the successful use of cytotoxic B12 derivatives for cancer therapy. 

The activity of MMPs is subject to complex regulation, involving both transcriptional and posttranslational mechanisms. The latter involves a group of endogenous protein inhibitors known as tissue inhibitors of metaUoproteinases (TlMPs), of which there are several. The balance of these enzymes is a major determinant of extracellular matrix control (58). TIMPs have been radiolabeled for imaging studies but have not yet been validated in vivo (59). 

Table 13.2 Climcal Imaging Studies Using Radiolabeled Annexin V Analogs...

Compared to conventional automated synthesis, the radiochemical yield and purity of the compound obtained by microreactor processing were higher and also synthesis time was shorter [28]. Multiple doses of 2-deoxy-2-[ F]fluoro-D-glucose for positron emission tomography imaging studies in mice were prepared. Today, 2-deoxy-2-[ F]fluoro-D-glucose is routinely produced in about 50 min with the use of expensive commercial synthesizers and the radiolabeled compound for 10-100 doses is produced in a single mn. 

The same group reported the simultaneous radiolabeling (with DOTA-anchored 4Cu) and fluorescence studies, coupled with biodistribution in vivo and in vitro (92). It is believed that appropriately functionalized SWNTs can efficiently reach tumor tissues in mice with no apparent toxicity (159). Furthermore, water-solubilised carbon nanotubes are nontoxic when taken up by cells even in high concentration (92). These studies have been complemented by the recent PET imaging of water-soluble 86Y labelled carbon nanotubes in vivo (mice) (160,161), to explore the potential usefulness of carbon nanocarriers as scaffolds for drug delivery. The tissue biodistribution and pharmacokinetics of model DOTA functionalized nanotubes have been explored in vivo (mouse model). MicroPET images indicated accumulation of activity mainly in the kidney, liver, spleen, and to a much less... 

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