In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 25, No. 18_suppl ( 2007-06-20), p. 2537-2537
Abstract:
2537 Background: Strategies to monitor molecular & cellular responses to novel cell cycle targeting agents are vital to provide proof of their mechanism & biological activity. In developing biomarkers for the novel chk1 inhibitor, PF-477736, we demonstrated that gemcitabine chemotherapy induced a significant increase, or flare, in uptake of the PET tracer, 3’-deoxy-3’flurothymidine (FLT), into tumor xenografts 24 h after dosing (Proc ASCO 24:A3045, 2006). We postulated that an early flare in FLT may also occur following gemcitabine therapy in human tumors. Methods: Eligible patients had at least 1 malignant lesion identified by CT scan outside of a previous radiation field. Patients received a baseline FLT-PET scan day-1 to -4 relative to 1st dose of gemcitabine at 1,000 mg/m 2 , and a post dose FLT- PET scan 22–26 h after gemcitabine. Endpoints were FLT uptake as assessed by: SUV; a qualitative scoring system; and tumor-to-background (T:B) ratios using liver, mediastinum and bone marrow as references. Results: Six of 8 planned patients with 14 index lesions have been accrued in this pilot study. 4/6 patients demonstrated increased uptake of FLT as defined by 〉 50% increase in SUV or T:B ratio in at least 1 lesion. Analysing all index lesions showed an increase in FLT-uptake post gemcitabine as assessed by a 4 point qualitative scoring system from 1.6±0.2 to 2.7±0.1 (p=0.01) or T:B 1.1±0.2 to 2.0±0.3 (p 〈 0.01) using liver as a reference. Interestingly in contrast to increased uptake in tumors, uptake of FLT in bone marrow was reduced from an SUV of 6.4±0.6 to 3.4±0.7 (p 〈 0.01) following gemcitabine. Conclusion: Following treatment with gemcitabine there was an early flare in uptake of FLT into many tumors. In contrast, uptake in bone marrow was reduced. FLT-PET appears to be a promising tool to monitor the cell cycle response of both tumor and bone marrow to cytotoxic chemotherapy. No significant financial relationships to disclose.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2007.25.18_suppl.2537
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2007
detail.hit.zdb_id:
2005181-5
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