Interventional therapy of head and neck cancer with lipid nanoparticle-carried rhenium 186 radionuclide.
OBJECTIVE
Minimally invasive interventional cancer therapy with drug-carrying lipid nanoparticles (ie, liposomes) via convection-enhanced delivery by an infusion pump can increase intratumoral drug concentration and retention while facilitating broad distribution throughout solid tumors. The authors investigated the utility of liposome-carrying beta-emitting radionuclides to treat head and neck cancer by direct intratumoral infusion in nude rats.


METHODS
Four groups of nude rats were subcutaneously inoculated with human tongue cancer cells. After tumors reached an average size of 1.6 cm(3), the treatment group received an intratumoral infusion of liposomal rhenium-186 ((186)Re) (185 MBq [5 mCi]/cm(3) tumor). Three control groups were intratumorally infused with unlabeled liposomes, unencapsulated (186)Re-perrhenate, or unencapsulated intermediate (186)Re compound ((186)Re-N,N-bis[2-mercaptoethyl]-N',N'-diethyl-ethylenediamine [BMEDA]). In vivo distribution of (186)Re activity was measured by planar gamma-camera imaging. Tumor therapy and toxicity were assessed by tumor size, body weight, and hematology.


RESULTS
Average tumor volume in the (186)Re-liposome group on posttreatment day 14 decreased to 87.7% +/- 20.1%, whereas tumor volumes increased to 395.0%-514.4% on average in the other three groups (P< .001 vs (186)Re-liposome). The (186)Re-liposomes provided much higher intratumoral retention of (186)Re activity, resulting in an average tumor radiation absorbed dose of 526.3 Gy +/- 93.3, whereas (186)Re-perrhenate and (186)Re-BMEDA groups had only 3.3 Gy +/- 1.2 and 13.4 Gy +/- 9.2 tumor doses, respectively. No systemic toxicity was observed.


CONCLUSIONS
Liposomal (186)Re effectively treated head and neck cancer with minimal side effects after convection-enhanced interventional delivery. These results suggest the potential of liposomal (186)Re for clinical application in interventional therapy of cancer.
French
J Tyler
JT
Department of Otolaryngology-Head and Neck Surgery, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MSC 7800, San Antonio, TX 78229-3900, USA.
Goins
Beth
B
Saenz
Marcela
M
Li
Shihong
S
Garcia-Rojas
Xavier
X
Phillips
William T
WT
Otto
Randal A
RA
Bao
Ande
A
D000818:Animals; D001835:Body Weight; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D006801:Humans; D007260:Infusion Pumps; D036502:Infusions, Intralesional; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D053758:Nanoparticles; D011829:Radiation Dosage; D011868:Radioisotopes; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D051381:Rats; D011923:Rats, Nude; D012211:Rhenium / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D013997:Time Factors; D014062:Tongue Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D047368:Tumor Burden
D008055:Lipids; D008081:Liposomes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C015428:perrhenate; D012211:Rhenium