Accessible Requires Authentication Published by De Gruyter July 26, 2019

Radioguided surgery: physical principles and an update on technological developments

Ali Pashazadeh and Michael Friebe


Radioguided surgery (RGS) is the use of radiation detection probes and handheld gamma cameras in surgery rooms to identify radioactively labeled lesions inside the body with an aim to improve surgical outcome. In today’s surgery, application of these devices is a well-established practice, which provides surgeons with real-time information to guide them to the site of a lesion. In recent years, there have been several major improvements in the technology and design of gamma probes and handheld gamma cameras, enhancing their applications in surgical practices. Handheld gamma cameras, for example, are now moving from single-modality to dual-modality scanners that add anatomical data to the physiologic data, and with that provide more clinical information of the tissue under study. Also, in the last decade, a radioguided surgical technique based on the Cerenkov radiation was introduced, with more improved sensitivity in identifying radioactively labeled lesions. Additionally, recent advances in hybrid tracers have led to more efficient detection of lesions labeled with these tracers. Besides, it seems that combining medical robotics and augmented reality technology with current radioguided surgical practices potentially will change the delivery and performance of RGS in the near future. The current paper aims to give an overview of the physics of RGS and summarizes recent advances in this field that have a potential to improve the application of radioguided surgical procedures in the management of cancer.

Funding source: Federal Ministry of Education and Research (BMBF) of Germany

Award Identifier / Grant number: 03IPT7100X

Funding statement: This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors. The chair of catheter technologies is financially supported by the Federal Ministry of Education and Research (BMBF) of Germany (Grand Number 03IPT7100X).

  1. Conflict of interest statement: The authors of this paper report no conflict of interest.


[1] Herrmann K, Nieweg OE, Povoski SP. Radioguided surgery: current applications and innovative directions in clinical practice. Springer; 2016. Search in Google Scholar

[2] Selverstone B, Sweet WH, Robinson CV. The clinical use of radioactive phosphorus in the surgery of brain tumors. Ann Surg 1949;130:643.10.1097/00000658-194910000-00007 Search in Google Scholar

[3] Harris C, Bigelow R, Francis J, Kelley G, Bell P. A CsI (Tl)-crystal surgical scintillation probe. Nucleonics 1956;14:102–8. Search in Google Scholar

[4] Soluri A, Pani R. Miniaturized gamma camera with very high spatial resolution. Google Patents; 2001. Search in Google Scholar

[5] Kotzassarlidou M, Hatzipavlidou B, Makridou A, Kostaki P, Salem N. Practical considerations in selecting and using intraoperative gamma probes. Nucl Instrum Methods Phys Res A 2004;527:110–2.10.1016/j.nima.2004.03.085 Search in Google Scholar

[6] Matheoud R, Giorgione R, Valzano S, Sacchetti G, Colombo E, Brambilla M. Minimum acceptable sensitivity of intraoperative gamma probes used for sentinel lymph node detection in melanoma patients. Phys Med 2014;30:822–6.2470400210.1016/j.ejmp.2014.03.006 Search in Google Scholar

[7] Karyagar S, Karatepe O, Bender O, Mulazimoglu M, Ozpacaci T, Uyanik E, et al. Tc-99m radio-guided completion thyroidectomy for differentiated thyroid carcinoma. Indian J Nucl Med 2010;25:12–5.10.4103/0972-3919.6359320844663 Search in Google Scholar

[8] Canavese G, Gipponi M, Catturich A, Di Somma C, Vecchio C, Rosato F, et al. Sentinel lymph node mapping in early-stage breast cancer: technical issues and results with vital blue dye mapping and radioguided surgery. J Surg Oncol 2000;74:61–8.10.1002/1096-9098(200005)74:1<61::AID-JSO14>3.0.CO;2-910861612 Search in Google Scholar

[9] Rzyman W, Hagen OM, Dziadziuszko R, Kobierska-Gulida G, Karmolinski A, Lothe IM, et al. Intraoperative, radio-guided sentinel lymph node mapping in 110 nonsmall cell lung cancer patients. Ann Thorac Surg 2006;82:237–42.1679822110.1016/j.athoracsur.2006.01.094 Search in Google Scholar

[10] Graafland NM, Valdes Olmos RA, Meinhardt W, Bex A, van der Poel HG, van Boven HH, et al. Nodal staging in penile carcinoma by dynamic sentinel node biopsy after previous therapeutic primary tumour resection. Eur Urol 2010;58:748–51.2063398110.1016/j.eururo.2010.06.036 Search in Google Scholar

[11] Vermeeren L, Valdes Olmos RA, Meinhardt W, Bex A, van der Poel HG, Vogel WV, et al. Intraoperative radioguidance with a portable gamma camera: a novel technique for laparoscopic sentinel node localisation in urological malignancies. Eur J Nucl Med Mol Imaging 2009;36:1029–36.10.1007/s00259-009-1100-619288098 Search in Google Scholar

[12] Gulec SA, Hoenie E, Hostetter R, Schwartzentruber D. PET probe-guided surgery: applications and clinical protocol. World J Surg Oncol 2007;5:65.10.1186/1477-7819-5-6517555587 Search in Google Scholar

[13] Francis CL, Nalley C, Fan C, Bodenner D, Brendan C. Stack J. 18F-fluorodeoxyglucose and 131I Radioguided Surgical Management of Thyroid Cancer. Otolaryngol Head Neck Surg 2012;146:26–32.10.1177/0194599811423007 Search in Google Scholar

[14] Renda A, Iovino F, Capasso L, Ricciardelli L, Tammaro V, Acampa W. Radioimmunoguided surgery in colorectal cancer: a 6-year experience with four different technical solutions. Semin Surg Oncol 1998;15:226–30.982937710.1002/(SICI)1098-2388(199812)15:4<226::AID-SSU8>3.0.CO;2-5 Search in Google Scholar

[15] Porziella V, Cesario A, Lococo F, Cafarotti S, Margaritora S, D’Errico G, et al. The radioguided 111In-pentetreotide surgery in the management of ACTH-secreting bronchial carcinoid. Eur Rev Med Pharmacol Sci 2011;15:587–91.21796863 Search in Google Scholar

[16] KleinJan GH, Bunschoten A, Brouwer OR, van den Berg NS, Valdés-Olmos RA, van Leeuwen FWB. Multimodal imaging in radioguided surgery. Clin Transl Imaging 2013;1:433–44.10.1007/s40336-013-0039-6 Search in Google Scholar

[17] Rubello D, Giannini S, De Carlo E, Mariani G, Muzzio PC, Rampin L, et al. Minimally invasive (99m)Tc-sestamibi radioguided surgery of parathyroid adenomas. Panminerva Med 2005;47:99–107.16210995 Search in Google Scholar

[18] van Hulsteijn LT, van der Hiel B, Smit JWA, Stokkel MP, Corssmit EPM. Intraoperative detection of ganglioneuromas with 123I-MIBG. Clin Nucl Med 2012;37:768–71.10.1097/RLU.0b013e31825add9b22785506 Search in Google Scholar

[19] Povoski SP, Hall NC, Murrey Jr DA, Sharp DS, Hitchcock CL, Mojzisik CM, et al. Multimodal imaging and detection strategy with 124I-labeled chimeric monoclonal antibody cG250 for accurate localization and confirmation of extent of disease during laparoscopic and open surgical resection of clear cell renal cell carcinoma. Surg Innov 2013;20:59–69.10.1177/1553350612438416 Search in Google Scholar

[20] Petty L, Mojzisik C, Hinkle G, Ignaszewski J, Loesch J, Berens A, et al. Radioimmunoguided surgery-a phase-I/II study using I-125 labeled to 17-1A IGG (2A) in patients with colorectal-cancer. Antibody Immunocon Radiopharm 1991;4:603–11. Search in Google Scholar

[21] Rubello D, Salvatori M, Ardito G, Mariani G, Al-Nahhas A, Gross M, et al. Iodine-131 radio-guided surgery in differentiated thyroid cancer: outcome on 31 patients and review of the literature. Biomed Pharmacother 2007;61:477–81.1776139710.1016/j.biopha.2007.07.010 Search in Google Scholar

[22] Serrano J, Rayo JI, Infante JR, Domínguez L, García-Bernardo L, Durán C, et al. Radioguided surgery in brain tumors with thallium-201. Clin Nucl Med 2008;33:838–40.10.1097/RLU.0b013e31818bf26a19033782 Search in Google Scholar

[23] Beyer T, Townsend DW, Brun T, Kinahan PE. A combined PET/CT scanner for clinical oncology. J Nucl Med 2000;41:1369.10945530 Search in Google Scholar

[24] Seo Y, Mari C, Hasegawa BH. Technological development and advances in single-photon emission computed tomography/computed tomography. Semin Nucl Med 2008;38:177–98.1839617810.1053/j.semnuclmed.2008.01.001 Search in Google Scholar

[25] Townsend DW. Dual-modality imaging: combining anatomy and function. J Nucl Med 2008;49:938–55.1848310110.2967/jnumed.108.051276 Search in Google Scholar

[26] Pani R, Pellegrini R, Cinti M, Polito C, Orlandi C, Fabbri A, et al. Integrated ultrasound and gamma imaging probe for medical diagnosis. J Instrum 2016;11:C03037.10.1088/1748-0221/11/03/C03037 Search in Google Scholar

[27] Alqahtani M, Lees J, Bugby S, Jambi L, Perkins A. Lymphoscintigraphic imaging study for quantitative evaluation of a small field of view (SFOV) gamma camera. J Instrum 2015;10:P07011.10.1088/1748-0221/10/07/P07011 Search in Google Scholar

[28] Tanha K, Pashazadeh AM, Pogue BW. Review of biomedical Čerenkov luminescence imaging applications. Biomed Opt Express 2015;6:3053–65.2630976610.1364/BOE.6.003053 Search in Google Scholar

[29] Grootendorst M, Cariati M, Kothari A, Tuch D, Purushotham A. Cerenkov luminescence imaging (CLI) for image-guided cancer surgery. Clin Transl Imaging 2016;4:353–66.2773862610.1007/s40336-016-0183-x Search in Google Scholar

[30] Jelley J. Cerenkov radiation and its applications. Br J Appl Sci Technol 1955;6:227. Search in Google Scholar

[31] Beattie BJ, Thorek DL, Schmidtlein CR, Pentlow KS, Humm JL, Hielscher AH. Quantitative modeling of Cerenkov light production efficiency from medical radionuclides. PLoS One 2012;7:e31402.2236363610.1371/journal.pone.0031402 Search in Google Scholar

[32] Ruggiero A, Holland JP, Lewis JS, Grimm J. Cerenkov luminescence imaging of medical isotopes. J Nucl Med 2010;51:1123–30.10.2967/jnumed.110.07652120554722 Search in Google Scholar

[33] Thorek D, Robertson R, Bacchus WA, Hahn J, Rothberg J, Beattie BJ, et al. Cerenkov imaging-a new modality for molecular imaging. Am J Nucl Med Mol Imaging 2012;2:163–73.23133811 Search in Google Scholar

[34] Robertson R, Germanos MS, Li C, Mitchell GS, Cherry SR, Silva MD. Optical imaging of Cerenkov light generation from positron-emitting radiotracers. Phys Med Biol 2009;54:N355.1963608210.1088/0031-9155/54/16/N01 Search in Google Scholar

[35] Klein JS, Mitchell G, Cherry S. Quantitative assessment of Cerenkov luminescence for radioguided brain tumor resection surgery. Phys Med Biol 2017;62:4183.10.1088/1361-6560/aa664128287074 Search in Google Scholar

[36] Spinelli AE, Schiariti MP, Grana CM, Ferrari M, Cremonesi M, Boschi F. Cerenkov and radioluminescence imaging of brain tumor specimens during neurosurgery. J Biomed Opt 2016;21:50502.10.1117/1.JBO.21.5.05050227156713 Search in Google Scholar

[37] Holland JP, Normand G, Ruggiero A, Lewis JS, Grimm J. Intraoperative imaging of positron emission tomographic radiotracers using Cerenkov luminescence emissions. Mol Imaging 2011;10:177–86.21496448 Search in Google Scholar

[38] Liu H, Carpenter CM, Jiang H, Pratx G, Sun C, Buchin MP, et al. Intraoperative imaging of tumors using Cerenkov luminescence endoscopy: a feasibility experimental study. J Nucl Med 2012;53:1579–84.10.2967/jnumed.111.09854122904353 Search in Google Scholar

[39] Carpenter CM, Ma X, Liu H, Sun C, Pratx G, Wang J, et al. Cerenkov luminescence endoscopy: improved molecular sensitivity with β-emitting radiotracers. J Nucl Med 2014;55:1905–9.10.2967/jnumed.114.13910525300598 Search in Google Scholar

[40] Madru R, Tran TA, Axelsson J, Ingvar C, Bibic A, Stahlberg F, et al. 68Ga-labeled superparamagnetic iron oxide nanoparticles (SPIONs) for multi-modality PET/MR/Cherenkov luminescence imaging of sentinel lymph nodes. Am J Nucl Med Mol Imaging 2014;4:60–9. Search in Google Scholar

[41] Hu H, Cao X, Kang F, Wang M, Lin Y, Liu M, et al. Feasibility study of novel endoscopic Cerenkov luminescence imaging system in detecting and quantifying gastrointestinal disease: first human results. Eur Radiol 2015;25:1814–22.10.1007/s00330-014-3574-225577521 Search in Google Scholar

[42] Song T, Liu X, Qu Y, Liu H, Bao C, Leng C, et al. A novel endoscopic Cerenkov luminescence imaging system for intraoperative surgical navigation. Mol Imaging 2015;14:443–9.26431810 Search in Google Scholar

[43] Thorek DL, Abou DS, Beattie BJ, Bartlett RM, Huang R, Zanzonico PB, et al. Positron lymphography: multimodal, high-resolution, dynamic mapping and resection of lymph nodes after intradermal injection of 18F-FDG. J Nucl Med 2012;53:1438–45.2287274110.2967/jnumed.112.104349 Search in Google Scholar

[44] Fan D, Zhang X, Zhong L, Liu X, Sun Y, Zhao H, et al. 68Ga-labeled 3PRGD2 for dual PET and Cerenkov Luminescence Imaging of orthotopic human glioblastoma. Bioconjug Chem 2015;26:1054–60.10.1021/acs.bioconjchem.5b00169 Search in Google Scholar

[45] Glaser AK, Zhang R, Davis SC, Gladstone DJ, Pogue BW. Time-gated Cherenkov emission spectroscopy from linear accelerator irradiation of tissue phantoms. Opt lett 2012;37:1193–5.2246619210.1364/OL.37.001193 Search in Google Scholar

[46] Jolesz FA, Shtern F. The Operating Room of the Future: Report of the National Cancer Institute Workshop,“Imaging-Guided Stereotactic Tumor Diagnosis and Treatment“. Invest Radiol 1992;27:326–8.160162610.1097/00004424-199204000-00016 Search in Google Scholar

[47] Yamamoto S, Kuroda K, Senda M. Development of an MR-compatible gamma probe for combined MR/RI guided surgery. Phys Med Biol 2004;49:3379–88.1537902010.1088/0031-9155/49/15/005 Search in Google Scholar

[48] Camillocci ES, Bellini F, Bocci V, Collamati F, De Lucia E, Faccini R, et al. Polycrystalline para-terphenyl scintillator adopted in a β detecting probe for radio-guided surgery. J Phys Conf 2015;620:012009.10.1088/1742-6596/620/1/012009 Search in Google Scholar

[49] Donnarumma R, Bocci V, Capparella E, Collamati F, Cremonesi M, Ferrari M, et al. A novel radioguided surgery technique exploiting beta-decay. Phys Medica 2016;32:104–5.10.1016/j.ejmp.2016.01.362 Search in Google Scholar

[50] Solfaroli Camillocci E, Schiariti M, Bocci V, Carollo A, Chiodi G, Colandrea M, et al. First ex vivo validation of a radioguided surgery technique with beta-radiation. Phys Med 2016;32:1139–44.2760124810.1016/j.ejmp.2016.08.018 Search in Google Scholar

[51] Spadola S, Verdier M-A, Pinot L, Esnault C, Dinu N, Charon Y, et al. Design optimization and performances of an intraoperative positron imaging probe for radioguided cancer surgery. J Instrum 2016;11:P12019.10.1088/1748-0221/11/12/P12019 Search in Google Scholar

[52] Yamamoto S, Matsumoto K, Sakamoto S, Tarutani K, Minato K, Senda M. An intra-operative positron probe with background rejection capability for FDG-guided surgery. Ann Nucl Med 2005;19:23–28.10.1007/BF0298633115770969 Search in Google Scholar

[53] van der Poel HG, Buckle T, Brouwer OR, Olmos RAV, van Leeuwen FW. Intraoperative laparoscopic fluorescence guidance to the sentinel lymph node in prostate cancer patients: clinical proof of concept of an integrated functional imaging approach using a multimodal tracer. Eur Urol 2011;60:826–33.10.1016/j.eururo.2011.03.02421458154 Search in Google Scholar

[54] Fuerst B, Sprung J, Pinto F, Frisch B, Wendler T, Simon H, et al. First robotic SPECT for minimally invasive sentinel lymph node mapping. IEEE Trans Med Imaging 2016;35:830–8.10.1109/TMI.2015.249812526561283 Search in Google Scholar

[55] van Oosterom MN, Simon H, Mengus L, Welling MM, van der Poel HG, van den Berg NS, et al. Revolutionizing (robot-assisted) laparoscopic gamma tracing using a drop-in gamma probe technology. Am J Nucl Med Mol Imaging 2016;6:1–17.27069762 Search in Google Scholar

[56] Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. Lancet Oncol 2012;13:790–801.10.1016/S1470-2045(12)70211-522658655 Search in Google Scholar

[57] Sullivan R, Alatise OI, Anderson BO, Audisio R, Autier P, Aggarwal A, et al. Global cancer surgery: delivering safe, affordable, and timely cancer surgery. Lancet Oncol 2015;16:1193–224.10.1016/S1470-2045(15)00223-526427363 Search in Google Scholar

Received: 2018-01-30
Accepted: 2019-01-08
Published Online: 2019-07-26
Published in Print: 2020-01-28

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