Abstract | BACKGROUND: METHODS: In vitro cell viability and cell cycle arrest of human ovarian cancer cells were assessed upon different treatment conditions. For therapy studies, nude mice (n = 8) were injected subcutaneously with IGROV1 human ovarian carcinoma cells and received a single dose of 6 MBq (177)Lu-DOTA-chCE7 alone or in combination with 600 μg PTX (31.6 mg/kg). Tumour growth delay and survival were determined. To investigate whether PTX can influence the tumour uptake of the radioimmunoconjugates (RICs), a biodistribution study (n = 4) and SPECT/CT images were acquired 120 h post injections of 2 MBq (177)Lu-DOTA-chCE7 alone or in combination with 600 μg PTX. RESULTS: Lu-DOTA-chCE7 in combination with PTX revealed a significantly decreased cell viability of ovarian carcinoma cells in vitro and was effective in a synergistic manner (combination index < 1). PTX increased the RIT efficacy by arresting cells in the radiosensitive G2/M phase of the cell cycle 24 h post treatment start. In vivo combination therapy including (177)Lu-DOTA-chCE7 and PTX resulted in a significantly prolonged overall survival (55 days vs. 18 days/PTX and 29 days/RIT), without weight loss and/or signs of toxicity. Biodistribution studies revealed no significant difference in tumour uptakes of (177)Lu-DOTA-chCE7 72 h post injection regardless of an additional PTX administration. CONCLUSIONS: Combination of anti-L1CAM (177)Lu-RIT with PTX is a more effective therapy resulting in a prolonged overall survival of human ovarian carcinoma-bearing nude mice compared with either monotherapy. The combination is promising for future clinical applications.
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Authors | Dennis Lindenblatt, Eliane Fischer, Susan Cohrs, Roger Schibli, Jürgen Grünberg |
Journal | EJNMMI research
(EJNMMI Res)
Vol. 4
Issue 1
Pg. 54
(Dec 2014)
ISSN: 2191-219X [Print] Germany |
PMID | 26116117
(Publication Type: Journal Article)
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