In vivo evaluation of cisplatin-loaded superabsorbent polymer microspheres for use in chemoembolization of VX2 liver tumors.
OBJECTIVE
To investigate the pharmacokinetics and efficacy of chemoembolization with a cisplatin-loaded superabsorbent polymer (SAP) suspension in a rabbit model with transplanted liver VX2 tumors.


METHODS
VX2 tumors were implanted into the left lobe of the liver in eight rabbits. Embolization of the proper hepatic artery was performed with cisplatin-loaded or unloaded SAP. In the cisplatin-loaded SAP group (n = 4), 5 mg of SAP (106-150 μm) loading 2.35 mg of cisplatin and 0.5 mL of ionic contrast material (ioxaglic acid 320 mgI/mL) was injected into the proper hepatic artery. In the control group (hepatic arterial infusion [HAI] + SAP; n = 4), 5 mg of SAP loading 0.5 mL of ioxaglic acid alone was injected after a bolus infusion of an equivalent amount of cisplatin. Sequential change of the plasma platinum concentration within the first 24 hours was measured. Blood sampling and histopathologic examination were performed at 1-week follow-up. Magnetic resonance (MR) images were used to calculate the growth rate of the VX2 tumor.


RESULTS
All animals underwent successful embolization. Both total and free plasma platinum mean concentrations within the first 24 hours remained lower in the cisplatin-loaded SAP group, although without statistical significance (P > .05). The mean tumor growth rate was significantly lower in the cisplatin-loaded SAP group than the control group (20% vs 116%; P = .049). Histopathologic examination revealed coagulative necrosis to nontumorous liver parenchyma in two rabbits in the cisplatin-loaded SAP group, although no deaths occurred.


CONCLUSIONS
These results suggested that chemoembolization with cisplatin-loaded SAP was a safe and tolerable treatment and was more effective in suppressing the tumor growth.
Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan. n-maeda@radiol.med.osaka-u.ac.jp
Noboru
N
Maeda
Keigo
K
Osuga
Kouki
K
Shimazu
Eiichi
E
Morii
Koji
K
Mikami
Shinichi
S
Hori
Tetsuro
T
Nakazawa
Hiroki
H
Higashihara
Kaname
K
Tomoda
Hironobu
H
Nakamura
Noriyuki
N
Tomiyama
D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity; D003287:Contrast Media / Q000008:administration & dosage; D004337:Drug Carriers; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D007485:Ioxaglic Acid / Q000008:administration & dosage; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008863:Microspheres; D011145:Polyvinyls / Q000737:chemistry*; D011817:Rabbits; D047368:Tumor Burden / Q000187:drug effects
D000180:Acrylic Resins; D000970:Antineoplastic Agents; D003287:Contrast Media; D004337:Drug Carriers; D011145:Polyvinyls; C569390:acrylic acid-vinyl alcohol copolymer; D002945:Cisplatin; D007485:Ioxaglic Acid