Journal
NUCLEAR MEDICINE AND BIOLOGY
Volume 40, Issue 5, Pages 630-637Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.nucmedbio.2013.03.005
Keywords
Ductal carcinoma in situ (DCIS); Intraoperative detection; Indium-111; Trastuzumab (Herceptin); Gamma probe; Fab fragments
Funding
- Ontario Institute for Cancer Research
- Province of Ontario
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Introduction: Our aim was to conduct a Phase I clinical trial to determine the feasibility of intraoperative detection of tumor margins in HER2 positive breast carcinoma using a hand-held gamma-probe following administration of In-111-DTPA-trastuzumab Fab fragments. Accurate delineation of tumor margins is important for preventing local recurrence. Methods: Six patients with HER2-positive in situ or invasive ductal carcinoma were administered 74 MBq (0.5 mg) of In-111-DTPA-trastuzumab Fab fragments and counts in the tumor, surgical cavity wall and en face margins were measured intraoperatively at 72 h post-injection using the Navigator or C-Trak gamma-probes. Margins were evaluated histologically. Quantitative whole body planar imaging was performed to estimate radiation absorbed doses using OLINDA/EXM software. SPECT imaging of the thorax was performed to evaluate tumor uptake. The pharmacokinetics of elimination from the blood and plasma were determined over 72 h. Results: There were no acute adverse reactions from In-111-DTPA-trastuzumab Fab fragments and no changes in hematological or biochemical indices were found over a 3 month period. In-111-DTPA-trastuzumab Fab fragments exhibited a biphasic elimination from the blood and plasma with t(1/2)alpha = 11.9 h and 7.5 h, respectively, and t(1/2)beta = 26.6 and 20.7 h, respectively. The radiopharmaceutical accumulated in the liver, spleen and kidneys. SPECT imaging did not reveal tumor in any patient. The mean effective dose was 0.146 mSv/MBq (10.8 mSv for 74 MBq). Counts in excised tumors were low but were higher than in margins. Margins in two patients harboured tumor but this was not correlated with counts obtained using the gamma-probes. Surgical cavity counts were high and likely due to detection of gamma-photons outside the surgical field. Conclusion: We conclude that it was not feasible, at least at the administered amount of radioactivity used in this study, to reliably detect the margins of disease in patients with in situ or invasive ductal carcinoma intraoperatively using a hand-held gamma-probe and In-111-DTPA-trastuzumab Fab fragments due to low uptake in the tumor and involved margins. (C) 2013 Elsevier Inc. All rights reserved.
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