Copper-64-pyruvaldehyde-bis(N(4)-methylthiosemicarbazone) for the prevention of tumor growth at wound sites following laparoscopic surgery: monitoring therapy response with microPET and magnetic resonance imaging.
Laparoscopic colectomy for curable colon cancer may result in the development of abdominal wall implants because of disseminated disease and the favorable environment of the wound site for cell implantation. Injection of disaggregated human GW39 colon cancer cells into the hamster peritoneum represents a model of tumor spillage that may occur during dissection, manipulation, resection, and extraction of tumor during surgery in the clinical setting. Using this well-established animal model, we tested the efficacy of (64)Cu-pyruvaldehyde-bis(N(4)-methylthiosemicarbazone) ((64)Cu-PTSM) in inhibiting tumor cell implantation in trocar wound sites. Anesthetized hamsters had four 5-mm trocars inserted through the anterior abdominal wall. GW39 cells ( approximately 3.2 x 10(4) cells in 0.5 ml) were injected into the peritoneum through a midline incision. Ten min later, hamsters were randomized to receive 5, 3, or 1 mCi of (64)Cu-PTSM through the same midline incision. High-resolution magnetic resonance imaging and microPET were used to monitor tumor volume and morphology after surgery. After 7 weeks, animals were sacrificed, and trocar and midline wounds were harvested for macroscopic and histological analysis. No macroscopic tumor was found in any of the group treated with 5 mCi of (64)Cu-PTSM, whereas 96% of the wound sites in the group treated with saline had macroscopic tumor growth (P < 0.001). This study demonstrates the therapeutic potential of (64)Cu-PTSM in inhibiting cancer cell implantation and growth at doses well below the maximum tolerated dose, with no signs of toxicity to the hamsters.
Lewis
Jason S
JS
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Connett
Judith M
JM
Garbow
Joel R
JR
Buettner
Thomas L
TL
Fujibayashi
Yasuhisa
Y
Fleshman
James W
JW
Welch
Michael J
MJ
D000009:Abdominal Muscles / Q000473:pathology; D000008:Abdominal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D003301:Copper Radioisotopes; D006224:Cricetinae; D010535:Laparoscopy / Q000009:adverse effects*; D008279:Magnetic Resonance Imaging; D008647:Mesocricetus; D009366:Neoplasm Seeding; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000494:pharmacology; D013882:Thiosemicarbazones / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D023041:Xenograft Model Antitumor Assays
D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C052629:copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex