Chemoradionuclide therapy with 186Re-labeled liposomal doxorubicin in combination with radiofrequency ablation for effective treatment of head and neck cancer in a nude rat tumor xenograft model.
OBJECTIVE
To determine the therapeutic efficacy of rhenium 186 ((186)Re)-labeled PEGylated liposomal doxorubicin ((186)Re-liposomal doxorubicin) in combination with radiofrequency (RF) ablation of human head and neck squamous cell carcinoma (HNSCC) xenograft in nude rats.


METHODS
This investigation was approved by the animal care committee. Sixty nude rats with subcutaneously implanted HNSCC xenografts (six per group) were treated with (a) RF ablation (70 °C for 5 minutes), (b) PEGylated liposomes, (c) liposomal doxorubicin, (d) (186)Re-PEGylated liposomes (1295 MBq/kg), (e) (186)Re-liposomal doxorubicin (555 MBq/kg), (f) PEGylated liposomes plus RF ablation, (g) liposomal doxorubicin plus RF ablation, (h) (186)Re-PEGylated liposomes plus RF ablation, or (i) (186)Re-liposomal doxorubicin plus RF ablation. Six rats did not receive any treatment (control group). Tumor uptake in (186)Re therapy groups was monitored with small-animal single photon emission computed tomography for 5 days. Therapeutic efficacy was monitored for 6 weeks with measurement of tumor volume, calculation of the percentage injected dose of fluorine 18 fluorodeoxyglucose (FDG) in tumor from small-animal positron emission tomography (PET) images, and determination of viable tumor volume at histopathologic examination. Significant differences between groups were determined with analysis of variance.


RESULTS
The average tumor volume (± standard deviation) on the day of therapy was 1.32 cm(3) ± 0.17. At 6 weeks after therapy, control of tumor growth was better with (186)Re-liposomal doxorubicin than with liposomal doxorubicin alone (tumor volume, 2.26 cm(3) ± 0.89 vs 5.43 cm(3) ± 0.93, respectively; P < .01). The use of RF ablation with liposomal doxorubicin and (186)Re-liposomal doxorubicin further improved tumor control (tumor volume, 2.05 cm(3) ± 1.36 and 1.49 cm(3) ± 1.47, respectively). The tumor growth trend correlated with change in percentage of injected dose of FDG in tumor for all groups (R(2) = 0.85, P < .001). Viable tumor volume was significantly decreased in the group treated with (186)Re-liposomal doxorubicin plus RF ablation (0.54 cm(3) ± 0.38; P < .001 vs all groups except (186)Re-liposomal doxorubicin alone).


CONCLUSIONS
Triple and dual therapies had an observable trend ((186)Re-liposomal doxorubicin plus RF ablation > (186)Re-liposomal doxorubicin > liposomal doxorubicin plus RF ablation > liposomal doxorubicin) of improved tumor growth control and decreased viable tumor compared with other therapies. FDG PET could be used as a noninvasive surrogate marker for tumor growth and viability in this tumor model.
Department of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, Mail Code 7800, San Antonio, TX 78229-3900, USA.
Anuradha
A
Soundararajan
Gerald D
GD
Dodd
Ande
A
Bao
William T
WT
Phillips
Linda M
LM
McManus
Thomas J
TJ
Prihoda
Beth A
BA
Goins
D000704:Analysis of Variance; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000628:therapy*; D017115:Catheter Ablation; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D004357:Drug Synergism; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy*; D007553:Isotope Labeling; D008081:Liposomes; D009683:Nuclear Medicine / Q000379:methods; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D011923:Rats, Nude; D012211:Rhenium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D014183:Transplantation, Heterologous
D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D019275:Radiopharmaceuticals; D012211:Rhenium; D004317:Doxorubicin