Combination radiofrequency ablation and intravenous radiolabeled liposomal Doxorubicin: imaging and quantification of increased drug delivery to tumors.
OBJECTIVE
To identify, with noninvasive imaging, the zone of radiopharmaceutical uptake after combination therapy with radiofrequency (RF) ablation and intravenous administration of technetium 99m ((99m)Tc) liposomal doxorubicin in a small-animal tumor model, and to quantify and correlate the uptake by using imaging and tissue counting of intratumoral doxorubicin accumulation.


METHODS
This study was approved by the animal care committee. Two phases of animal experiments were performed. In the first experiment, a single human head-and-neck squamous cell carcinoma tumor was grown in each of 10 male nude rats. Seven of these animals were treated with intravenous (99m)Tc-liposomal doxorubicin followed by RF tumor ablation at a mean temperature of 70 degrees C + or - 2 for 5 minutes, and three were treated with intravenous (99m)Tc-liposomal doxorubicin only. Combination single photon emission computed tomography-computed tomography (SPECT/CT) was performed at 15 minutes, 4 hours, and 20 hours after therapy. In the second experiment, two tumors each were grown in 11 rats, but only one of the tumors was ablated after intravenous administration of (99m)Tc-liposomal doxorubicin. SPECT/CT and planar scintigraphy were performed at the same posttreatment intervals applied in the first experiment, with additional planar imaging performed at 44 hours. After imaging, tissue counting in the excised tumors was performed. Radiotracer uptake, as determined with imaging and tissue counting, was quantified and compared. In a subset of three animals, intratumoral doxorubicin accumulation was determined with fluorimetry and correlated with the imaging and tissue-counting data.


RESULTS
At both SPECT/CT and planar scintigraphy, increased uptake of (99m)Tc-liposomal doxorubicin was visibly apparent in the ablated tumors. Results of quantitative analysis with both imaging and tissue counting confirmed significantly greater uptake in the RF ablation-treated tumors (P < .001). Intratumoral doxorubicin accumulation correlated closely with imaging (r = 0.9185-0.9871) and tissue-counting (r = 0.995) results.


CONCLUSIONS
Study results show that increased delivery of intravenous liposomal doxorubicin to tumors combined with RF ablation can be depicted and quantified with noninvasive imaging.
Head
Hayden W
HW
Departments of Radiology, Otolaryngology, and Pathology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, MC 7800, San Antonio, TX 78229-3900, USA.
Dodd
Gerald D
GD
Bao
Ande
A
Soundararajan
Anuradha
A
Garcia-Rojas
Xavier
X
Prihoda
Thomas J
TJ
McManus
Linda M
LM
Goins
Beth A
BA
Santoyo
Cristina A
CA
Phillips
William T
WT
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000601:surgery*; D017115:Catheter Ablation / Q000379:methods*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000601:surgery*; D006801:Humans; D021621:Imaging, Three-Dimensional; D007275:Injections, Intravenous; D016014:Linear Models; D008297:Male; D009368:Neoplasm Transplantation; D011857:Radiographic Image Interpretation, Computer-Assisted; D019275:Radiopharmaceuticals; D051381:Rats; D011923:Rats, Nude; D016284:Technetium Tc 99m Pentetate; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D004317:Doxorubicin; D016284:Technetium Tc 99m Pentetate