Breast-conserving surgery involves completely excising the tumour while limiting the amount of normal tissue removed, which is technically challenging to achieve, especially given the limited intraoperative guidance available to the surgeon. This study evaluates the feasibility of radioimmunoguided surgery (RIGS) to guide the detection and delineation of tumours intraoperatively. The 3D point-response function of a commercial gamma-ray-detecting probe (GDP) was determined as a function of radionuclide (131I, 111In, 99mTc), energy-window threshold, and collimator length (0.0–3.0-cm). This function was used to calculate the minimum detectable tumour volumes (MDTVs) and the minimum tumour-to-background activity concentration ratio (T:B) for effective delineation of a breast tumour model. The GDP had larger MDTVs and a higher minimum required T:B for tumour delineation with 131I than with 111In or 99mTc. It was shown that for 111In there was a benefit to using a collimator length of 0.5-cm. For the model used, the minimum required T:B required for effective tumour delineation was 5.2 ± 0.4. RIGS has the potential to significantly improve the accuracy of breast-conserving surgery; however, before these benefits can be realized, novel radiopharmaceuticals need to be developed that have a higher specificity for cancerous tissue in vivo than what is currently available. 1. Introduction In North America, over 60% of breast cancer patients receive breast-conserving surgery [1]. The primary goal of this operative procedure is the complete excision of the cancerous lesion, with a margin of grossly normal tissue. The purpose of this margin is to reduce the probability that microscopic disease remains. A secondary, conflicting goal is to limit the volume of normal tissue that is excised, thereby reducing patient morbidity and improving cosmesis. Achieving these goals is technically challenging, and incomplete excision occurs in 15–40% of breast-conserving operations, with pathologic evaluation revealing cancerous cells at the cut edge of the excised volume [2, 3]. Studies by Park et al. [4] and Peterson et al. [5] have independently shown that tumours with diameters greater than 2？cm have a higher likelihood of involved margins than smaller tumours. This may be attributed to the presence of nonpalpable disease at the boundaries of these tumours. This largely intra-ductal disease is difficult to detect using currently available guidance techniques that rely on anatomical differences between normal tissue and tumour [2, 6]. There is currently only limited
References
[1]
M. Morrow, C. Bucci, and A. Rademaker, “Medical contraindications are not a major factor in the underutilization of breast conserving therapy,” Journal of the American College of Surgeons, vol. 186, no. 3, pp. 269–274, 1998.
[2]
D. Aziz, E. Rawlinson, S. A. Narod et al., “The role of reexcision for positive margins in optimizing local disease control after breast-conserving surgery for cancer,” Breast Journal, vol. 12, no. 4, pp. 331–337, 2006.
[3]
F. J. Fleming, A. D. K. Hill, E. W. Mc Dermott, A. O'Doherty, N. J. O'Higgins, and C. M. Quinn, “Intraoperative margin assessment and re-excision rate in breast conserving surgery,” European Journal of Surgical Oncology, vol. 30, no. 3, pp. 233–237, 2004.
[4]
C. C. Park, M. Mitsumori, A. Nixon et al., “Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence,” Journal of Clinical Oncology, vol. 18, no. 8, pp. 1668–1675, 2000.
[5]
M. E. Peterson, D. J. Schultz, C. Reynolds, and L. J. Solin, “Outcomes in breast cancer patients relative to margin status after treatment with breast-conserving surgery and radiation therapy: the University of Pennsylvania experience,” International Journal of Radiation Oncology Biology Physics, vol. 43, no. 5, pp. 1029–1035, 1999.
[6]
S. E. Singletary, “Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy,” American Journal of Surgery, vol. 184, no. 5, pp. 383–393, 2002.
[7]
V. Lavoué, C. Nos, K. B. Clough et al., “Simplified technique of radioguided occult lesion localization (ROLL) plus sentinel lymph node biopsy (SNOLL) in breast carcinoma,” Annals of Surgical Oncology, vol. 15, no. 9, pp. 2556–2561, 2008.
[8]
R. S. Rampaul, M. Bagnall, H. Burrell, S. E. Pinder, A. J. Evans, and R. D. Macmillan, “Randomized clinical trial comparing radioisotope occult lesion localization and wire-guided excision for biopsy of occult breast lesions,” British Journal of Surgery, vol. 91, no. 12, pp. 1575–1577, 2004.
[9]
G. Paganelli, A. Luini, and U. Veronesi, “Radioguided occult lesion localization (ROLL) in breast cancer: maximizing efficacy, minimizing mutilation,” Annals of Oncology, vol. 13, no. 12, pp. 1839–1840, 2002.
[10]
W. Pavlicek, H. A. Walton, P. J. Karstaedt, and R. J. Gray, “Radiation Safety With Use of I-125 Seeds for Localization of Nonpalpable Breast Lesions,” Academic Radiology, vol. 13, no. 7, pp. 909–915, 2006.
[11]
R. J. Gray, B. A. Pockaj, P. J. Karstaedt, and M. C. Roarke, “Radioactive seed localization of nonpalpable breast lesions is better than wire localization,” American Journal of Surgery, vol. 188, no. 4, pp. 377–380, 2004.
[12]
S. P. Harlow, D. N. Krag, S. E. Ames, and D. L. Weaver, “Intraoperative ultrasound localization to guide surgical excision of nonpalpable breast carcinoma,” Journal of the American College of Surgeons, vol. 189, no. 3, pp. 241–246, 1999.
[13]
M. M. Moore, L. A. Whitney, L. Cerilli et al., “Intraoperative ultrasound is associated with clear lumpectomy margins for palpable infiltrating ductal breast cancer,” Annals of Surgery, vol. 233, no. 6, pp. 761–768, 2001.
[14]
F. D. Rahusen, A. H. M. Taets Van Amerongen, P. J. Van Diest, P. J. Borgstein, R. P. Bleichrodt, and S. Meijer, “Ultrasound-guided lumpectomy of nonpalpable breast cancers: a feasibility study looking at the accuracy of obtained margins,” Journal of Surgical Oncology, vol. 72, no. 2, pp. 72–76, 1999.
[15]
L. M. Lamki, A. U. Buzdar, S. E. Singletary et al., “Indium-111-labeled B72.3 monoclonal antibody in the detection and staging of breast cancer: a phase I study,” Journal of Nuclear Medicine, vol. 32, no. 7, pp. 1326–1332, 1991.
[16]
Y. Tang, J. Wang, D. A. Scollard et al., “Imaging of HER2/neu-positive BT-474 human breast cancer xenografts in athymic mice using 111In-trastuzumab (Herceptin) Fab fragments,” Nuclear Medicine and Biology, vol. 32, no. 1, pp. 51–58, 2005.
[17]
A. Orlova, T. Tran, C. Widstr？m, T. Engfeldt, A. E. Karlstr？m, and V. Tolmachev, “Pre-clinical evaluation of [111In]-benzyl-DOTA-Z HER2:342, a potential agent for imaging of HER2 expression in malignant tumors,” International Journal of Molecular Medicine, vol. 20, no. 3, pp. 397–404, 2007.
[18]
J. M. Esteban, B. Felder, C. Ahn, J. F. Simpson, H. Battifora, and J. E. Shively, “Prognostic relevance of carcinoembryonic antigen and estrogen receptor status in breast cancer patients,” Cancer, vol. 74, no. 5, pp. 1575–1583, 1994.
[19]
P. L. Jager, M. A. de Korte, M. N. Lub-de Hooge et al., “Molecular imaging: what can be used today,” Cancer Imaging, vol. 5, pp. S27–S32, 2005.
[20]
D. M. Goldenberg and H. A. Nabi, “Breast cancer imaging with radiolabeled antibodies,” Seminars in Nuclear Medicine, vol. 29, no. 1, pp. 41–48, 1999.
[21]
D. M. Goldenberg, E. E. Kim, and F. H. DeLand, “Radioimmunodetection of cancer with radioactive antibodies to carcinoembryonic antigen,” Cancer Research, vol. 40, no. 8, pp. 2984–2992, 1980.
[22]
I. G. Sergides, R. C. T. Austin, and M. C. Winslet, “Radioimmunodetection: technical problems and methods of improvement,” European Journal of Surgical Oncology, vol. 25, no. 5, pp. 529–539, 1999.
[23]
S. J. DeNardo, “Radioimmunodetection and therapy of breast cancer,” Seminars in Nuclear Medicine, vol. 35, no. 2, pp. 143–151, 2005.
[24]
K. McLarty, B. Cornelissen, D. A. Scollard, S. J. Done, K. Chun, and R. M. Reilly, “Associations between the uptake of 111In-DTPA-trastuzumab, HER2 density and response to trastuzumab (Herceptin) in athymic mice bearing subcutaneous human tumour xenografts,” European Journal of Nuclear Medicine and Molecular Imaging, vol. 36, no. 1, pp. 81–93, 2009.
[25]
K. McLarty and R. M. Reilly, “Molecular imaging as a tool for personalized and targeted anticancer therapy,” Clinical Pharmacology and Therapeutics, vol. 81, no. 3, pp. 420–424, 2007.
[26]
D. T. Geddes, “Inside the lactating breast: the latest anatomy research,” Journal of Midwifery and Women's Health, vol. 52, no. 6, pp. 556–563, 2007.
[27]
S. Y. F. Chu, L. P. Ekstrom, and R. B. Firestone, “The Lund/LBNL Nuclear Data Search,” 1999.
[28]
D. P. Kwo, H. B. Barber, H. H. Barrett, T. S. Hickernell, and J. M. Woolfenden, “Comparison of NaI(Tl), CdTe, and HgI2 surgical probes: effect of scatter compensation on probe performance,” Medical Physics, vol. 18, no. 3, pp. 382–389, 1991.
[29]
H. H. Barrett and W. Swindell, Radiological Imaging: The Theory of Image Formation, Detection, and Processing, vol. 1, Academic Press, 1981.
[30]
L. A. Currie, “Limits for qualitative detection and quantitative determination: application to radiochemistry,” Analytical Chemistry, vol. 40, no. 3, pp. 586–593, 1968.
[31]
R. P. Beaney, A. A. Lammertsma, and T. Jones, “Positron emission tomography for in-vivo measurement of regional blood flow, oxygen utilisation, and blod volume in patients with breast carcinoma,” Lancet, vol. 1, no. 8369, pp. 131–134, 1984.
[32]
H. B. Barber, H. H. Barrett, T. S. Hickernell et al., “Comparison of NaI(Tl), CdTe, and HgI2 surgical probes: physical characterization,” Medical Physics, vol. 18, no. 3, pp. 373–381, 1991.
[33]
F. Daghighian, J. C. Mazziotta, E. J. Hoffman et al., “Intraoperative beta probe: a device for detecting tissue labeled with positron or electron emitting isotopes during surgery,” Medical Physics, vol. 21, no. 1, pp. 153–157, 1994.
[34]
M. Tornai, Small area beta and gamma detectors for functional nuclear emission imaging, Ph.D. thesis, University of California Los Angeles, Los Angeles, Calif, USA, 1997.
[35]
S. Yamamoto, K. Matsumoto, and M. Senda, “Optimum threshold setting for a positron-sensitive probe with background rejection capability,” Annals of Nuclear Medicine, vol. 18, no. 3, pp. 251–256, 2004.
[36]
S. Yamamoto, K. Matsumoto, S. Sakamoto, K. Tarutani, K. Minato, and M. Senda, “An intra-operative positron probe with background rejection capability for FDG-guided surgery,” Annals of Nuclear Medicine, vol. 19, no. 1, pp. 23–28, 2005.
[37]
E. J. Hoffman, M. P. Tornai, M. Janecek, B. E. Patt, and J. S. Iwanczyk, “Intraoperative probes and imaging probes,” European Journal of Nuclear Medicine, vol. 26, no. 8, pp. 913–935, 1999.
[38]
R. R. Raylman, S. J. Fisher, R. S. Brown, S. P. Ethier, and R. L. Wahl, “Fluorine-18-fluorodeoxyglucose-guided breast cancer surgery with a positron-sensitive probe: validation in preclinical studies,” Journal of Nuclear Medicine, vol. 36, no. 10, pp. 1869–1874, 1995.
