Mixed-ligand complexes of yttrium-90 dialkyldithiocarbamates with 1,10-phenanthroline as a possible agent for therapy of hepatocellular carcinoma

Abstract

Yttrium-90 is a radioelement which has found wide use in targeted radionuclide therapy because of its attractive physical and chemical properties. Radioembolisation of hepatocellular carcinoma with radiolabelled Lipiodol is a method of choice. We have synthesised a series of alkyldithiocarbamate yttrium complexes, easily extracted into Lipiodol due to their high lipophilicity. Among the prepared series, a new radioconjugate, which is stable over an extended period of time, has been prepared, and could represent a potential treatment procedure for hepatocellular carcinoma.

Transarterial Radioembolization (TARE) Agents beyond 90Y-Microspheres

“…The radiotracer showed increased stability compared to oxinate and high tumour uptake, but its stability was not satisfactory enough. Other compounds mentioned in the literature include dithiocarbamate/phenanthroline 90 Y-complex [133] and di(2-ethylhexyl) orthophosphoric acid (P204), initially developed for solvent extraction of metals [134], with no biological data. Ligands used are summarised in Figure 3.…”

Transarterial Radionuclide Therapy with 188Re-Labelled Lipiodol

“…However, the high energy gamma emission and long half-life of iodine-131 (E βmax = 0.81 MeV; Eγ = 364 keV (81 %); t 1/2 = 8.02 d), as well as its high production cost have hindered its more widespread use. Yttrium-90, a pure beta-emitter (E βmax = 2.28 MeV; t 1/2 = 64.0 h, max tissue penetration = 12 mm) [25], and rhenium-188 (E βmax = 2.12 MeV; Eγ = 155 keV (15 %); t 1/2 = 16.9 h, max tissue penetration = 11 mm) [26] have been proposed as an advantageous alternative to iodine-131. As highlighted in this special issue, rhenium-188 appears promising, and several approaches have been proposed to label Lipiodol with this isotope, some of them being under clinical evaluation.…”

Labeling of Hinokitiol with 90Y for Potential Radionuclide Therapy of Hepatocellular Carcinoma

“…Thus, the combination of Lipiodol embolization with Yttrium-90 irradiation seems attractive. To date, attempts to label Lipiodol with Yttrium-90 have been disap pointing, with complicated syntheses and/or low stability [22][23][24][25]. It is worth mentioning that Lipiodol labeling is not done with the formation of a covalent bond between the Lip iodol and the chelate, except for EDTB [22], but instead is reached through solubilization of a lipophilic chelate into the oily medium.…”

“…For comparison, other lipophilic radiotracers described in the literature to label Lipiodol were prepared according to previously published methods [18,23,25] and their release studied. An amount of 1 mL of freshly prepared 90 Y-oxine (37-74 MBq), 90 Y(DEDC) 3 (Phen) (37-74 MBq) and 188 Re-SSS (82-87 MBq) in Lipiodol phase were collected with a syringe, and the above procedure was applied.…”

“…Besides its already mentioned use in micro spheres for radioembolization, it has been used in peptide receptor radionuclide therapy (PRRT) and radioimmunotherapy (RIT) of various tumor types [21]. 90 Y-labeling of Lip iodol has also been described [22][23][24][25]. With the exception of 131 I-radiolabeling, Lipiodo labeling is reached through solubilization of a lipophilic chelate into the oily medium.…”