Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, ON, Canada M4N 3M5.
Nucl Med Biol. 2013 Jul;40(5):630-7. doi: 10.1016/j.nucmedbio.2013.03.005. Epub 2013 Apr 22.
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 γ-probe following administration of (111)In-DTPA-trastuzumab Fab fragments. Accurate delineation of tumor margins is important for preventing local recurrence.
Six patients with HER2-positive in situ or invasive ductal carcinoma were administered 74MBq (0.5mg) of (111)In-DTPA-trastuzumab Fab fragments and counts in the tumor, surgical cavity wall and en face margins were measured intraoperatively at 72h post-injection using the Navigator or C-Trak γ-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 72h.
There were no acute adverse reactions from (111)In-DTPA-trastuzumab Fab fragments and no changes in hematological or biochemical indices were found over a 3month period. (111)In-DTPA-trastuzumab Fab fragments exhibited a biphasic elimination from the blood and plasma with t1/2α=11.9h and 7.5h, respectively, and t1/2β=26.6 and 20.7h, respectively. The radiopharmaceutical accumulated in the liver, spleen and kidneys. SPECT imaging did not reveal tumor in any patient. The mean effective dose was 0.146mSv/MBq (10.8mSv for 74MBq). 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 γ-probes. Surgical cavity counts were high and likely due to detection of γ-photons outside the surgical field.
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 γ-probe and (111)In-DTPA-trastuzumab Fab fragments due to low uptake in the tumor and involved margins.
我们的目的是进行一项 I 期临床试验，以确定在 HER2 阳性乳腺癌患者中使用手持式 γ 探针在注射（111）In-DTPA-曲妥珠单抗 Fab 片段后术中检测肿瘤边缘的可行性。准确描绘肿瘤边缘对于预防局部复发非常重要。
六名 HER2 阳性原位或浸润性导管癌患者给予 74MBq（0.5mg）（111）In-DTPA-曲妥珠单抗 Fab 片段，并在注射后 72 小时内使用 Navigator 或 C-Trak γ 探针术中测量肿瘤、手术腔壁和正面边缘的计数。组织学评估边缘。使用 OLINDA/EXM 软件进行定量全身平面成像以估计辐射吸收剂量。进行胸部 SPECT 成像以评估肿瘤摄取。在 72 小时内确定从血液和血浆中消除的药代动力学。
（111）In-DTPA-曲妥珠单抗 Fab 片段无急性不良反应，3 个月内未发现血液学或生化指标变化。（111）In-DTPA-曲妥珠单抗 Fab 片段从血液和血浆中呈双相消除，t1/2α分别为 11.9h 和 7.5h，t1/2β分别为 26.6h 和 20.7h。放射性药物在肝脏、脾脏和肾脏中积累。SPECT 成像未在任何患者中发现肿瘤。平均有效剂量为 0.146mSv/MBq（74MBq 为 10.8mSv）。切除肿瘤中的计数较低，但高于边缘。两名患者的边缘有肿瘤，但与γ探针获得的计数无关。手术腔计数较高，可能是由于检测到手术场外的γ光子。
我们的结论是，至少在本研究中使用的放射性活度剂量下，使用手持式 γ 探针和（111）In-DTPA-曲妥珠单抗 Fab 片段术中可靠地检测原位或浸润性导管癌患者的疾病边缘是不可行的，因为肿瘤和受累边缘的摄取量低。
