Copper-64-pyruvaldehyde-bis(N4-methylthiosemicarbazone) for the prevention of tumor growth at wound sites following laparoscopic surgery: Monitoring therapy response with microPET and magnetic resonance imaging

Jason S. Lewis, Michael J. Welch, Judith M. Connett, Thomas L. Buettner, James W. Fleshman, Joel R. Garbow, Yasuhisa Fujibayashi

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (64Cu-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 (∼3.2 × 104 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 64Cu-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 64Cu-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 64Cu-PTSM in inhibiting cancer cell implantation and growth at doses well below the maximum tolerated dose, with no signs of toxicity to the hamsters.

Original languageEnglish
Pages (from-to)445-449
Number of pages5
JournalCancer research
Volume62
Issue number2
StatePublished - Jan 15 2002

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