Chemoradionuclide therapy with186re-labeled liposomal doxorubicin in combination with radiofrequency ablation for effective treatment of head and neck cancer in a nude rat tumor xenograft model

Anuradha Soundararajan, Gerald D. Dodd, Ande Bao, William T Phillips, Linda M Mcmanus, Thomas J. Prihoda, Beth A. Goins

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Abstract

Purpose: To determine the therapeutic efficacy of rhenium 186 ( 186Re)-labeled PEGylated liposomal doxorubicin (186Re- liposomal doxorubicin) in combination with radiofrequency (RF) ablation of human head and neck squamous cell carcinoma (HNSCC) xenograft in nude rats. Materials and 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) 186Re-PEGylated liposomes (1295 MBq/kg), (e) 186Re-liposomal doxorubicin (555 MBq/kg), (f) PEGylated liposomes plus RF ablation, (g) liposomal doxorubicin plus RF ablation, (h) 186Re-PEGylated liposomes plus RF ablation, or (i) 186Re-liposomal doxorubicin plus RF ablation. Six rats did not receive any treatment (control group). Tumor uptake in 186Re 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 cm3 ± 0.17. At 6 weeks after therapy, control of tumor growth was better with 186Re-liposomal doxorubicin than with liposomal doxorubicin alone (tumor volume, 2.26 cm3 ± 0.89 vs 5.43 cm3± 0.93, respectively; P <.01). The use of RF ablation with liposomal doxorubicin and 186Re-liposomal doxorubicin further improved tumor control (tumor volume, 2.05 cm3 ± 1.36 and 1.49 cm3 ± 1.47, respectively). The tumor growth trend correlated with change in percentage of injected dose of FDG in tumor for all groups (R2 = 0.85, P <.001). Viable tumor volume was significantly decreased in the group treated with 186Re-liposomal doxorubicin plus RF ablation (0.54 cm3 ± 0.38; P <.001 vs all groups except 186 Re-liposomal doxorubicin alone). Conclusion: Triple and dual therapies had an observable trend (186Re-liposomal doxorubicin plus RF ablation > 186Re-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.

Original languageEnglish (US)
Pages (from-to)813-823
Number of pages11
JournalRadiology
Volume261
Issue number3
DOIs
StatePublished - Dec 2011

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Nude Rats
Head and Neck Neoplasms
Heterografts
Neoplasms
Tumor Burden
Liposomes
Therapeutics
Positron-Emission Tomography
liposomal doxorubicin
Growth
Animal Care Committees
Rhenium
Fluorodeoxyglucose F18
Group Psychotherapy
Single-Photon Emission-Computed Tomography
Analysis of Variance

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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Chemoradionuclide therapy with186re-labeled liposomal doxorubicin in combination with radiofrequency ablation for effective treatment of head and neck cancer in a nude rat tumor xenograft model. / Soundararajan, Anuradha; Dodd, Gerald D.; Bao, Ande; Phillips, William T; Mcmanus, Linda M; Prihoda, Thomas J.; Goins, Beth A.

In: Radiology, Vol. 261, No. 3, 12.2011, p. 813-823.

Research output: Contribution to journalArticle

Soundararajan, Anuradha ; Dodd, Gerald D. ; Bao, Ande ; Phillips, William T ; Mcmanus, Linda M ; Prihoda, Thomas J. ; Goins, Beth A. / Chemoradionuclide therapy with186re-labeled liposomal doxorubicin in combination with radiofrequency ablation for effective treatment of head and neck cancer in a nude rat tumor xenograft model. In: Radiology. 2011 ; Vol. 261, No. 3. pp. 813-823.
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title = "Chemoradionuclide therapy with186re-labeled liposomal doxorubicin in combination with radiofrequency ablation for effective treatment of head and neck cancer in a nude rat tumor xenograft model",
abstract = "Purpose: To determine the therapeutic efficacy of rhenium 186 ( 186Re)-labeled PEGylated liposomal doxorubicin (186Re- liposomal doxorubicin) in combination with radiofrequency (RF) ablation of human head and neck squamous cell carcinoma (HNSCC) xenograft in nude rats. Materials and 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) 186Re-PEGylated liposomes (1295 MBq/kg), (e) 186Re-liposomal doxorubicin (555 MBq/kg), (f) PEGylated liposomes plus RF ablation, (g) liposomal doxorubicin plus RF ablation, (h) 186Re-PEGylated liposomes plus RF ablation, or (i) 186Re-liposomal doxorubicin plus RF ablation. Six rats did not receive any treatment (control group). Tumor uptake in 186Re 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 cm3 ± 0.17. At 6 weeks after therapy, control of tumor growth was better with 186Re-liposomal doxorubicin than with liposomal doxorubicin alone (tumor volume, 2.26 cm3 ± 0.89 vs 5.43 cm3± 0.93, respectively; P <.01). The use of RF ablation with liposomal doxorubicin and 186Re-liposomal doxorubicin further improved tumor control (tumor volume, 2.05 cm3 ± 1.36 and 1.49 cm3 ± 1.47, respectively). The tumor growth trend correlated with change in percentage of injected dose of FDG in tumor for all groups (R2 = 0.85, P <.001). Viable tumor volume was significantly decreased in the group treated with 186Re-liposomal doxorubicin plus RF ablation (0.54 cm3 ± 0.38; P <.001 vs all groups except 186 Re-liposomal doxorubicin alone). Conclusion: Triple and dual therapies had an observable trend (186Re-liposomal doxorubicin plus RF ablation > 186Re-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.",
author = "Anuradha Soundararajan and Dodd, {Gerald D.} and Ande Bao and Phillips, {William T} and Mcmanus, {Linda M} and Prihoda, {Thomas J.} and Goins, {Beth A.}",
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T1 - Chemoradionuclide therapy with186re-labeled liposomal doxorubicin in combination with radiofrequency ablation for effective treatment of head and neck cancer in a nude rat tumor xenograft model

AU - Soundararajan, Anuradha

AU - Dodd, Gerald D.

AU - Bao, Ande

AU - Phillips, William T

AU - Mcmanus, Linda M

AU - Prihoda, Thomas J.

AU - Goins, Beth A.

PY - 2011/12

Y1 - 2011/12

N2 - Purpose: To determine the therapeutic efficacy of rhenium 186 ( 186Re)-labeled PEGylated liposomal doxorubicin (186Re- liposomal doxorubicin) in combination with radiofrequency (RF) ablation of human head and neck squamous cell carcinoma (HNSCC) xenograft in nude rats. Materials and 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) 186Re-PEGylated liposomes (1295 MBq/kg), (e) 186Re-liposomal doxorubicin (555 MBq/kg), (f) PEGylated liposomes plus RF ablation, (g) liposomal doxorubicin plus RF ablation, (h) 186Re-PEGylated liposomes plus RF ablation, or (i) 186Re-liposomal doxorubicin plus RF ablation. Six rats did not receive any treatment (control group). Tumor uptake in 186Re 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 cm3 ± 0.17. At 6 weeks after therapy, control of tumor growth was better with 186Re-liposomal doxorubicin than with liposomal doxorubicin alone (tumor volume, 2.26 cm3 ± 0.89 vs 5.43 cm3± 0.93, respectively; P <.01). The use of RF ablation with liposomal doxorubicin and 186Re-liposomal doxorubicin further improved tumor control (tumor volume, 2.05 cm3 ± 1.36 and 1.49 cm3 ± 1.47, respectively). The tumor growth trend correlated with change in percentage of injected dose of FDG in tumor for all groups (R2 = 0.85, P <.001). Viable tumor volume was significantly decreased in the group treated with 186Re-liposomal doxorubicin plus RF ablation (0.54 cm3 ± 0.38; P <.001 vs all groups except 186 Re-liposomal doxorubicin alone). Conclusion: Triple and dual therapies had an observable trend (186Re-liposomal doxorubicin plus RF ablation > 186Re-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.

AB - Purpose: To determine the therapeutic efficacy of rhenium 186 ( 186Re)-labeled PEGylated liposomal doxorubicin (186Re- liposomal doxorubicin) in combination with radiofrequency (RF) ablation of human head and neck squamous cell carcinoma (HNSCC) xenograft in nude rats. Materials and 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) 186Re-PEGylated liposomes (1295 MBq/kg), (e) 186Re-liposomal doxorubicin (555 MBq/kg), (f) PEGylated liposomes plus RF ablation, (g) liposomal doxorubicin plus RF ablation, (h) 186Re-PEGylated liposomes plus RF ablation, or (i) 186Re-liposomal doxorubicin plus RF ablation. Six rats did not receive any treatment (control group). Tumor uptake in 186Re 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 cm3 ± 0.17. At 6 weeks after therapy, control of tumor growth was better with 186Re-liposomal doxorubicin than with liposomal doxorubicin alone (tumor volume, 2.26 cm3 ± 0.89 vs 5.43 cm3± 0.93, respectively; P <.01). The use of RF ablation with liposomal doxorubicin and 186Re-liposomal doxorubicin further improved tumor control (tumor volume, 2.05 cm3 ± 1.36 and 1.49 cm3 ± 1.47, respectively). The tumor growth trend correlated with change in percentage of injected dose of FDG in tumor for all groups (R2 = 0.85, P <.001). Viable tumor volume was significantly decreased in the group treated with 186Re-liposomal doxorubicin plus RF ablation (0.54 cm3 ± 0.38; P <.001 vs all groups except 186 Re-liposomal doxorubicin alone). Conclusion: Triple and dual therapies had an observable trend (186Re-liposomal doxorubicin plus RF ablation > 186Re-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.

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