Miscellaneous approaches

Various porphyrin derivatives are known to be tumour-avid agents and a rhenium labelled porphyrin derivative has been evaluated as a potential therapeutic modality. A water-soluble porphyrin-bearing carboxylate group (Figure 24.20) was labelled with radioactive rhenium, a mixture of 186Re and 188Re, prepared by irradiation of natural rhenium.

CO2H

ho2c ho2c co2h

CO2H

ho2c ho2c

HO2C

CO2H

co2h Figure 24.20

CO2H

co2h Figure 24.20

The two isotopes that were produced with this method were not separated.

was added to a solution of the buffer dissolved in a bicarbonate buffer system and stannous tartrate was added as a reductant. The actual chemical nature of the complex is not known and the radiochemical purity decreased from 98 to 35% when the complex was stored at room temperature. Biodistribution studies were carried out in fibrosarcoma-bearing Swiss mice. An uptake of more than 3.5%/g of tumour was observed 30min after the injection. The low stability of the complex was implicated in the fast clearance of the agent from non-target tissue and 24 h after the injection 89% of the activity showed renal clearance presumably as perrhenate.46 In this case the rhenium probably coordinates to the peripheral carboxylate groups and a more stable rhenium-porphyrin conjugate could be synthesised by incorporating donor groups that are better suited to rhenium in mid-low oxidation states.

Another ligand system that offers potential in the development of rhenium-based radiopharmaceuticals is that based on tridentate formylpyridyl thio-semicarbazones (Figure 24.21). A series of Re(III) complexes, [ReL2]+, where LH = a 2-formylpyridine thiosemicarbazone, have been synthesized. Thiosemi-carbazones are of considerable pharmacological interest since a number of derivatives have shown a broad spectrum of chemotherapeutic properties and their metal complexes often show enhanced biological activities. These thiosemi-carbazone ligands can be readily functionalized with biomolecules to provide in vivo specificity or to control lipophilicity and biodistribution of any metal

HO2C

S NHR

NHR Figure 24.21

S NHR

NHR Figure 24.21

complexes. In these complexes the rhenium atom is in a distorted octahedral environment with two tridentate deprotonated thiosemicarbazones binding as monoanionic ligands through the sulphur, pyridyl nitrogen and azamethinic nitrogen in a mer (azomethine nitrogen atoms trans) configuration.47 The compounds can be synthesized directly from perrhenate. Although radiolabel-ling of these compounds is yet to be published, these complexes are of particular interest in the development of radiopharmaceuticals, as they offer unique homoleptic complexes and the use of two tridentate chelating ligands binding in a mer fashion to form octahedral rhenium complexes. This does not result in syn/anti-isomeric mixtures which complicate the radiolabelling and pharmacokinetic properties of the well-known oxorhenium complexes formed with N2S2 ligands; also the complexes are stable and of a low molecular weight.

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