25 research outputs found
A kit formulation for the preparation of 188Re-lipiodol: preclinical studies and preliminary therapeutic evaluation in patients with unresectable hepatocellular carcinoma
A lyophilized kit formulation for the efficient labelling of lipiodol with generator-produced rhenium-188 is described. The preliminary preparation of the lipophilic complex bis-(diethyldithiocarbamato)nitrido rhenium-188 (188ReN-DEDC) was carried out using a two-vial kit containing S-methyl-N-methyl-dithiocarbazate, SnCl2 and sodium oxalate in the first vial, and diethyldithiocarbamate and a carbonate buffer in the second vial. After mixing of the reaction solution with lipiodol, the complex 188ReN-DEDC was quantitatively extracted and retained by this hydrophobic substance, thus allowing the stable incorporation of the beta-emitting radionuclide. The radiochemical purity of the complex 188ReN-DEDC was 97+/-2%. The activity extracted into the lipiodol phase was 96+/-3% of the initial activity, indicating that the complex 188ReN-DEDC was almost quantitatively removed from the aqueous reaction solution. In vitro stability studies in human plasma, at 37 degrees C, demonstrated the release of less than 15% of the activity within three half-lives. The biodistribution of Re-lipiodol in non-tumour-bearing Wistar rats at 6, 24, 48 and 72 h after intraportal venous injection showed one-third of total activity in the liver at 6 h, declining to 2% retention at 72 h. Bowel uptake at 6 and 24 h declined to low levels at 48 and 72 h. Renal activity peaked at 1.7%, diminishing to 0.6% over 48 h. Rat whole body gamma imaging showed gut activity in addition to hepatic uptake at 6 and 24 h, but only liver was evident from 48 to 72 h. Kidneys were not demonstrable at any imaging time point. In nine patients, activity was localized in the tumours immediately following intrahepatic arterial injection. Computed tomography/single-photon emission computed tomography (CT/SPECT) imaging at 1 and 24 h confirmed the retention of 188Re-lipiodol in the hepatoma, with minimal gut uptake and no lung activity over 24 h. These patients were subsequently treated with activities of 2.5-5 GBq of 188Re-lipiodol fractions without adverse effects. Six patients followed for up to 2 years in the pilot study achieved stable disease and there was objective partial response in one patient. Repeated treatments were performed on two to three occasions in three patients without evident toxicity. An additional patient given 6 GBq of 188Re-lipiodol demonstrated myelosuppression, which recovered with granulocyte colony-stimulating factor (GCSF) and platelet support. It is concluded that 188Re-lipiodol, prepared using our novel kit formulation, is stable in vivo and provides safe and effective therapy of unresectable hepatocellular carcinoma when given via the hepatic artery, either alone or in combination with transarterial chemoembolization
A kit formulation for the preparation of Re-188-lipiodol: preclinical studies and preliminary therapeutic evaluation in patients with unresectable hepatocellular carcinoma (vol 25, pg 691, 2004)
A lyophilized kit formulation for the efficient labelling of
lipiodol with generator-produced rhenium-188 is
described. The preliminary preparation of the lipophilic
complex bis-(diethyldithiocarbamato)nitrido rhenium-188
(188ReN-DEDC) was carried out using a two-vial kit
containing S-methyl-N-methyl-dithiocarbazate, SnCl2 and
sodium oxalate in the first vial, and diethyldithiocarbamate
and a carbonate buffer in the second vial. After mixing of
the reaction solution with lipiodol, the complex 188ReNDEDC
was quantitatively extracted and retained by
this hydrophobic substance, thus allowing the stable
incorporation of the b-emitting radionuclide. The
radiochemical purity of the complex 188ReN-DEDC was
97± 2%. The activity extracted into the lipiodol phase was
96± 3% of the initial activity, indicating that the complex
188ReN-DEDC was almost quantitatively removed from the
aqueous reaction solution. In vitro stability studies in
human plasma, at 378C, demonstrated the release of less
than 15% of the activity within three half-lives. The
biodistribution of 188Re-lipiodol in non-tumour-bearing
Wistar rats at 6, 24, 48 and 72 h after intraportal venous
injection showed one-third of total activity in the liver at 6 h,
declining to 2% retention at 72 h. Bowel uptake at 6 and
24 h declined to low levels at 48 and 72 h. Renal activity
peaked at 1.7%, diminishing to 0.6% over 48 h. Rat whole
body gamma imaging showed gut activity in addition to
hepatic uptake at 6 and 24 h, but only liver was evident
from 48 to 72 h. Kidneys were not demonstrable at any
imaging time point. In nine patients, activity was localized
in the tumours immediately following intrahepatic arterial
injection. Computed tomography/single-photon emission
computed tomography (CT/SPECT) imaging at 1 and 24 h
confirmed the retention of 188Re-lipiodol in the hepatoma,
with minimal gut uptake and no lung activity over 24 h.
These patients were subsequently treated with activities of
2.5–5 GBq of 188Re-lipiodol fractions without adverse
effects. Six patients followed for up to 2 years in the pilot
study achieved stable disease and there was objective
partial response in one patient. Repeated treatments were
performed on two to three occasions in three patients
without evident toxicity. An additional patient given 6 GBq
of 188Re-lipiodol demonstrated myelosuppression, which
recovered with granulocyte colony-stimulating factor
(GCSF) and platelet support. It is concluded that
188Re-lipiodol, prepared using our novel kit formulation, is
stable in vivo and provides safe and effective therapy of
unresectable hepatocellular carcinoma when given via
the hepatic artery, either alone or in combination with
transarterial chemoembolization