Abstract
Purpose
To develop imaging of lymphatics with resolution greater than that of lymphoscintigraphy using technetium-99 m neomannosyl human serum albumin (99mTc-MSA), we developed a Gallium-68 (68Ga) MSA for positron emission tomography (PET). This study is the first clinical trial to evaluate the feasibility of sentinel node detection using this novel 68Ga tracer for the management of non-small cell lung cancer.
Methods
We enrolled 34 patients (20 men, 14 women; mean age, 64.3 ± 10.4 years) who were candidates for lobectomy with mediastinal lymph node dissection for clinical stage I non-small cell lung cancer. 68Ga-MSA was administered in one injection into the peritumoral region, and lymphoscintigraphy was performed by PET/CT just before surgery. All harvested lymph nodes were cut into 2 mm slices and were ultimately diagnosed using formalin-fixed and paraffin-embedded sections with hematoxylin and eosin staining.
Results
The sentinel nodes were well visualized by PET/CT imaging from 15 to 120 min, and especially within 60 min, after injection. In all patients (100 %), sentinel nodes could be identified on PET/CT. The number of sentinel nodes identified was 1.9 ± 0.9 (range 1–5) per patient. The maximum standardized uptake values were 2882.2 ± 2124.3 in the tumor and 82.5 ± 159.0 in the sentinel nodes. Eight of 34 patients (23.5 %) had metastases in 13 sentinel nodes. No false-negative sentinel nodes were detected in any of the eight patients with N1 or N2 disease (0 %).
Conclusions
68Ga-MSA appears to be a promising tracer for sentinel node identification in non-small cell lung cancer.
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References
Hubbard MO, Fu P, Margevicius S, Dowlati A, Linden PA. Five-year survival does not equal cure in non-small cell lung cancer: a Surveillance, Epidemiology, and End Results-based analysis of variables affecting 10- to 18-year survival. J Thorac Cardiovasc Surg. 2012;143(6):1307–13. doi:10.1016/j.jtcvs.2012.01.078.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90. doi:10.3322/caac.20107.
Allen MS, Darling GE, Pechet TTV, et al. Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial. Ann Thorac Surg. 2006;81(3):1013–9; discussion 1019-20. doi:10.1016/j.athoracsur.2005.06.066.
Taghizadeh KA, Bagheri R, Tehranian S, Shojaee P, Sadeghi R, Krag D. Accuracy of sentinel node biopsy in the staging of non-small cell lung carcinomas: systematic review and meta-analysis of the literature. Lung Cancer. 2013;80(1):5–14. doi:10.1016/j.lungcan.2013.01.001.
Kim S, Kim HK, Kang D-Y, Jeong JM, Choi YH. Intra-operative sentinel lymph node identification using a novel receptor-binding agent (technetium-99 m neomannosyl human serum albumin, 99mTc-MSA) in stage I non-small cell lung cancer. Eur J Cardiothorac Surg. 2010;37(6):1450–6. doi:10.1016/j.ejcts.2010.01.012.
Nomori H, Ikeda K, Mori T, et al. Sentinel node identification in clinical stage Ia non-small cell lung cancer by a combined single photon emission computed tomography/computed tomography system. J Thorac Cardiovasc Surg. 2007;134(1):182–7. doi:10.1016/j.jtcvs.2007.02.013.
Schalin-Jäntti C, Ryhänen E, Heiskanen I, et al. Planar scintigraphy with 123I/99mTc-sestamibi, 99mTc-sestamibi SPECT/CT, 11C-methionine PET/CT, or selective venous sampling before reoperation of primary hyperparathyroidism? J Nucl Med. 2013;54(5):739–47. doi:10.2967/jnumed.112.109561.
Franzius C, Hermann K, Weckesser M, et al. Whole-body PET/CT with 11C-meta-hydroxyephedrine in tumors of the sympathetic nervous system: feasibility study and comparison with 123I-MIBG SPECT/CT. J Nucl Med. 2006;47(10):1635–42.
Choi JY, Jeong JM, Yoo BC, et al. Development of 68 Ga-labeled mannosylated human serum albumin (MSA) as a lymph node imaging agent for positron emission tomography. Nucl Med Biol. 2011;38(3):371–9. doi:10.1016/j.nucmedbio.2010.09.010.
Jeong JM, Hong MK, Kim YJ, et al. Development of 99mTc-neomannosyl human serum albumin (99mTc-MSA) as a novel receptor binding agent for sentinel lymph node imaging. Nucl Med Commun. 2004;25(12):1211–7.
Ueda K, Suga K, Kaneda Y, et al. Radioisotope lymph node mapping in nonsmall cell lung cancer: can it be applicable for sentinel node biopsy? Ann Thorac Surg. 2004;77(2):426–30. doi:10.1016/S0003-4975(03)01351-1.
Hicks R, Lau E, Binns D. Hybrid imaging is the future of molecular imaging. Biomed Imaging Interv J. 2007;3(3):e49. doi:10.2349/biij.3.3.e49.
Heuveling DA, van Schie A, Vugts DJ, et al. Pilot study on the feasibility of PET/CT lymphoscintigraphy with 89Zr-nanocolloidal albumin for sentinel node identification in oral cancer patients. J Nucl Med. 2013;54(4):585–9. doi:10.2967/jnumed.112.115188.
Heuveling DA, Visser GWM, Baclayon M, et al. 89Zr-nanocolloidal albumin-based PET/CT lymphoscintigraphy for sentinel node detection in head and neck cancer: preclinical results. J Nucl Med. 2011;52(10):1580–4. doi:10.2967/jnumed.111.089557.
Stroup SP, Kane CJ, Farchshchi-Heydari S, et al. Preoperative sentinel lymph node mapping of the prostate using PET/CT fusion imaging and Ga-68-labeled tilmanocept in an animal model. Clin Exp Metastasis. 2012;29(7):673–80. doi:10.1007/s10585-012-9498-9.
Kim HK, Kim S, Sung HK, Lee Y-S, Jeong JM, Choi YH. Comparison between preoperative versus intraoperative injection of technetium-99 M Neomannosyl human serum albumin for sentinel lymph node identification in early stage lung cancer. Ann Surg Oncol. 2012;19(4):1343–9. doi:10.1245/s10434-011-2130-4.
Shetty D, Lee YS, Jeong JM. 68 Ga-labeled radiopharmaceuticals for positron emission tomography. Nucl Med Mol Imaging. 2010;44(4):233–40.
Breeman WAP, Verbruggen AM. The 68Ge/68 Ga generator has high potential, but when can we use 68 Ga-labelled tracers in clinical routine? Eur J Nucl Med Mol Imaging. 2007;34(7):978–81. doi:10.1007/s00259-007-0387-4.
Kim JH, Lee JS, Kang KW, et al. Whole-body distribution and radiation dosimetry of (68)Ga-NOTA-RGD, a positron emission tomography agent for angiogenesis imaging. Cancer Biother Radiopharm. 2012;27(1):65–71. doi:10.1089/cbr.2011.1061.
Fazaeli Y, Jalilian AR, Amini MM, et al. Development of a 68 Ga-fluorinated porphyrin complex as a possible PET imaging agent. Nucl Med Mol Imaging. 2012;46(1):20–6. doi:10.1007/s13139-011-0109-5.
Eo JS, Paeng JC, Lee S, et al. Angiogenesis imaging in myocardial infarction using 68 Ga-NOTA-RGD PET: characterization and application to therapeutic efficacy monitoring in rats. Coron Artery Dis. 2013;24(4):303–11. doi:10.1097/MCA.0b013e3283608c32.
Wilhelm AJ, Mijnhout GS, Franssen EJ. Radiopharmaceuticals in sentinel lymph-node detection: an overview. Eur J Nucl Med. 1999;26(4 Suppl):S36–42.
Acknowledgement
This work was supported by a National Research Foundation of Korea (NRF) Grant funded by the Ministry of Education, Science and Technology (No: 2012012166) and by a Korea University Grant (K1132181).
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The authors declare that they have no conflict of interest.
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Jae Seon Eo and Hyun Koo Kim contributed equally to this work.
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Eo, J.S., Kim, H.K., Kim, S. et al. Gallium-68 Neomannosylated Human Serum Albumin-Based PET/CT Lymphoscintigraphy for Sentinel Lymph Node Mapping in Non-small Cell Lung Cancer. Ann Surg Oncol 22, 636–641 (2015). https://doi.org/10.1245/s10434-014-3986-x
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DOI: https://doi.org/10.1245/s10434-014-3986-x