Intraoperative therapy with liposomal drug delivery: retention and distribution in human head and neck squamous cell carcinoma xenograft model.
The focus of this study is to investigate the retention and biodistribution of technetium-99m ((99m)Tc) labeled liposomes in a human head and neck squamous cell carcinoma (HNSCC) positive surgical margin animal xenograft model. Positive surgical margin (with margin<1mm) in HNSCC is associated with significant higher mortality and recurrence rate when compared to clear margin. An immediate intraoperative application of liposome-carried therapeutic agents may treat the residual disease intraoperatively and improve long term survival in these patients. To understand the feasibility of this intraoperative therapy in HNSCC, the in vivo behavior of liposomes after intraoperative administration of (99m)Tc-labeled liposomes using non-invasive nuclear imaging was investigated in an animal xenograft model. Neutral and cationic (99m)Tc-labeled liposomes of 100 nm, 1 microm and 2 microm in diameter (6 study groups with 4 rats per study group) were injected into a nude rat HNSCC positive surgical margin xenograft model. Intratumoral, locoregional, and systemic retention and distribution of the (99m)Tc-liposomes were determined using non-invasive nuclear imaging and post-mortem organ distribution. The (99m)Tc-liposomes demonstrated high locoregional retention rate of 55.9+/-3.7% to 72.9+/-2.4% at 44 h after intraoperative injection to allow significant radiation to the surgical cavity if therapeutic radionuclides were used. Overall, the cationic liposomes demonstrated higher intratumoral retention rate, and the neutral liposomes showed greater retention in the paratumoral cavity (p<0.05 respectively). In conclusion, intraoperative therapy with liposome carried radionuclide drug delivery system carries great potential in treating unresectable HNSCC, and further study using therapeutic radionuclide should be explored.
Department of Otolaryngology-Head and Neck Surgery, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Sean X
SX
Wang
Ande
A
Bao
William T
WT
Phillips
Beth
B
Goins
Stephanie J
SJ
Herrera
Cristina
C
Santoyo
Frank R
FR
Miller
Randal A
RA
Otto
D000825:Animal Structures / Q000378:metabolism; D000818:Animals; D001826:Body Fluids / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005029:Ethylenediamines / Q000737:chemistry; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery*; D006801:Humans; D015552:Injections, Intralesional; D007430:Intraoperative Care / Q000379:methods*; D007668:Kidney / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000737:chemistry; D010316:Particle Size; D011874:Radiometry; D051381:Rats; D011923:Rats, Nude; D012867:Skin / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D055114:X-Ray Microtomography; D023041:Xenograft Model Antitumor Assays
D005029:Ethylenediamines; D008081:Liposomes; D015609:Organotechnetium Compounds