open access

Vol 20, No 1 (2017)
Review paper
Submitted: 2016-07-14
Accepted: 2016-12-30
Published online: 2017-01-31
Get Citation

Radioguided surgery with radiolabeled somatostatin analogs: not only in GEP-NETs

Vincenzo Cuccurullo, Giuseppe Danilo Di Stasio, Luigi Mansi
·
Pubmed: 28218348
·
Nucl. Med. Rev 2017;20(1):49-56.

open access

Vol 20, No 1 (2017)
Reviews
Submitted: 2016-07-14
Accepted: 2016-12-30
Published online: 2017-01-31

Abstract

Radioguided surgery (RGS) is a surgical technique that, using intra-operative probes, enables the surgeon to identify tissues preoperatively “marked” by a radiopharmaceutical. Somatostatin receptors (SSTRs) are present in the majority of neuroendocrine cells and may be over-expressed not only by tumor cells, but also by endothelial cells of peritumoral vessels, inflammatory cells and cells of the immune system, such as activated lymphocytes, monocytes and epithelioid cells. This extra neoplastic uptake is the rationale for the use of radiolabeled somatostatin analogs (SSAs) either in some tumors not expressing SSTRs or in various non-oncological diseases. The crucial point of RGS technique lays in the establishment of a favorable tumor-to-background ratio (TBR). A wide range of probe systems are available with different detectors and many radiopharmaceuticals have been experimented and utilized, mainly using g-detection probes; in order to widen RGS application field, newer approaches with b– or b+ emitting radioisotopes have also been proposed. Together with the consolidated clinical use, a promising and effective employment of RGS may be found in neuroendocrine tumors (NETs) using 111In-pentetreotide (OCT). RGS with OCT has been demonstrated useful in the management of patients with gastroenteropancreatic (GEP) tumors, lung, brain and breast cancer. Preoperative scintigraphy or PET with DOTA-peptides combined with RGS increases the rate of successful surgery. Preliminary studies with b– probes using 90Y-SSA suggest the possible interest of this approach in patients undergoing peptide receptor radiotherapy.

Abstract

Radioguided surgery (RGS) is a surgical technique that, using intra-operative probes, enables the surgeon to identify tissues preoperatively “marked” by a radiopharmaceutical. Somatostatin receptors (SSTRs) are present in the majority of neuroendocrine cells and may be over-expressed not only by tumor cells, but also by endothelial cells of peritumoral vessels, inflammatory cells and cells of the immune system, such as activated lymphocytes, monocytes and epithelioid cells. This extra neoplastic uptake is the rationale for the use of radiolabeled somatostatin analogs (SSAs) either in some tumors not expressing SSTRs or in various non-oncological diseases. The crucial point of RGS technique lays in the establishment of a favorable tumor-to-background ratio (TBR). A wide range of probe systems are available with different detectors and many radiopharmaceuticals have been experimented and utilized, mainly using g-detection probes; in order to widen RGS application field, newer approaches with b– or b+ emitting radioisotopes have also been proposed. Together with the consolidated clinical use, a promising and effective employment of RGS may be found in neuroendocrine tumors (NETs) using 111In-pentetreotide (OCT). RGS with OCT has been demonstrated useful in the management of patients with gastroenteropancreatic (GEP) tumors, lung, brain and breast cancer. Preoperative scintigraphy or PET with DOTA-peptides combined with RGS increases the rate of successful surgery. Preliminary studies with b– probes using 90Y-SSA suggest the possible interest of this approach in patients undergoing peptide receptor radiotherapy.

Get Citation

Keywords

somatostatin analogs, 111In-pentetreotide, radioguided surgery, intraoperative probes, neuroendocrine tumors, breast cancer, lung cancer, brain cancer

About this article
Title

Radioguided surgery with radiolabeled somatostatin analogs: not only in GEP-NETs

Journal

Nuclear Medicine Review

Issue

Vol 20, No 1 (2017)

Article type

Review paper

Pages

49-56

Published online

2017-01-31

Page views

1945

Article views/downloads

1760

DOI

10.5603/NMR.2017.0003

Pubmed

28218348

Bibliographic record

Nucl. Med. Rev 2017;20(1):49-56.

Keywords

somatostatin analogs
111In-pentetreotide
radioguided surgery
intraoperative probes
neuroendocrine tumors
breast cancer
lung cancer
brain cancer

Authors

Vincenzo Cuccurullo
Giuseppe Danilo Di Stasio
Luigi Mansi

References (85)
  1. Myers WG, Vanderleeden JC. Radioiodine-125. J Nucl Med. 1960; 1: 149–164.
  2. Schneebaum S, Even-Sapir E, Cohen M, et al. Clinical applications of gamma-detection probes - radioguided surgery. Eur J Nucl Med. 1999; 26(4 Suppl): S26–S35.
  3. Reubi J, Waser B, Schaer JC, et al. Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med. 2001; 28(9): 836–846.
  4. Mansi L, Cuccurullo V. Diagnostic imaging in neuroendocrine tumors. J Nucl Med. 2014; 55(10): 1576–1577.
  5. Cuccurullo V, Cascini GL, Tamburrini O, et al. Less frequent requests for In-111 pentreotide and its brothers of endocrinological interest. Minerva Endocrinol. 2011; 36(1): 41–52.
  6. Vidal-Sicart S, Olmos RV. Synergism of SPECT/CT and portable gamma cameras for intraoperative sentinel lymph node biopsy in melanoma, breast cancer, and other malignancies. Clinical and Translational Imaging. 2016; 4(5): 313–327.
  7. Intra M, de Cicco C, Gentilini O, et al. Radioguided localisation (ROLL) of non-palpable breast lesions and simultaneous sentinel lymph node biopsy (SNOLL): the experience of the European Institute of Oncology. Eur J Nucl Med Mol Imaging. 2007; 34(6): 957–958.
  8. Tiffet O, Perrot JL, Gentil-Perret A, et al. Sentinel lymph node detection in primary melanoma with preoperative dynamic lymphoscintigraphy and intraoperative gamma probe guidance. Br J Surg. 2004; 91(7): 886–892.
  9. Mariani G, Moresco L, Viale G, et al. Radioguided sentinel lymph node biopsy in breast cancer surgery. J Nucl Med. 2001; 42(8): 1198–1215.
  10. Postma EL, Verkooijen HM, van Esser S, et al. ROLL study group. Efficacy of 'radioguided occult lesion localisation' (ROLL) versus 'wire-guided localisation' (WGL) in breast conserving surgery for non-palpable breast cancer: a randomised controlled multicentre trial. Breast Cancer Res Treat. 2012; 136(2): 469–478.
  11. Medina-Franco H, Abarca-Pérez L, García-Alvarez MN, et al. Radioguided occult lesion localization (ROLL) versus wire-guided lumpectomy for non-palpable breast lesions: a randomized prospective evaluation. J Surg Oncol. 2008; 97(2): 108–111.
  12. Infante JR, Lorente R, Rayo JI, et al. [Use of radioguided surgery in the surgical treatment of osteoid osteoma]. Rev Esp Med Nucl Imagen Mol. 2015; 34(4): 225–229.
  13. Desiato V, Melis M, Amato B, et al. Minimally invasive radioguided parathyroid surgery: A literature review. Int J Surg. 2016; 28 Suppl 1: S84–S93.
  14. Camillocci ES, Baroni G, Bellini F, et al. A novel radioguided surgery technique exploiting β(-) decays. Sci Rep. 2014; 4: 4401.
  15. Collamati F, Bellini F, Bocci V, et al. Time Evolution of DOTATOC Uptake in Neuroendocrine Tumors in View of a Possible Application of Radioguided Surgery with β- Decay. J Nucl Med. 2015; 56(10): 1501–1506.
  16. Collamati F, Pepe A, Bellini F, et al. Toward radioguided surgery with β- decays: uptake of a somatostatin analogue, DOTATOC, in meningioma and high-grade glioma. J Nucl Med. 2015; 56(1): 3–8.
  17. Daghighian F, Mazziotta JC, Hoffman EJ, et al. Intraoperative beta probe: a device for detecting tissue labeled with positron or electron emitting isotopes during surgery. Med Phys. 1994; 21(1): 153–157.
  18. Hoffman EJ, Tornai MP, Janecek M, et al. Intraoperative probes and imaging probes. Eur J Nucl Med. 1999; 26(8): 913–935.
  19. Barber HB, Barrett HH, Hickernell TS, et al. Comparison of NaI(Tl), CdTe, and HgI2 surgical probes: physical characterization. Med Phys. 1991; 18(3): 373–381.
  20. Kwo DP, Barber HB, Barrett HH, et al. Comparison of NaI(T1), CdTe, and HgI2 surgical probes: effect of scatter compensation on probe performance. Med Phys. 1991; 18(3): 382–389.
  21. Mariani G, Vaiano A, Nibale O, et al. Is the "ideal" gamma-probe for intraoperative radioguided surgery conceivable? J Nucl Med. 2005; 46(3): 388–390.
  22. Zanzonico P, Heller S. The intraoperative gamma probe: basic principles and choices available. Semin Nucl Med. 2000; 30(1): 33–48.
  23. Herrmann K, Nieweg OE, Povoski SP. Radioguided Surgery: Current Applications and Innovative Directions in Clinical Practice. Springer Verlag, Berlin 2016.
  24. Tsuchimochi M, Hayama K. Intraoperative gamma cameras for radioguided surgery: technical characteristics, performance parameters, and clinical applications. Phys Med. 2013; 29(2): 126–138.
  25. Heller S, Zanzonico P. Nuclear probes and intraoperative gamma cameras. Semin Nucl Med. 2011; 41(3): 166–181.
  26. Denmeade KA, Constable C, Reed WM. Use of (99m)Tc 2-methoxyisobutyl isonitrile in minimally invasive radioguided surgery in patients with primary hyperparathyroidism: A narrative review of the current literature. J Med Radiat Sci. 2013; 60(2): 58–66.
  27. Duarte GM, dos Santos CC, Torresan RZ, et al. Radioguided surgery using intravenous 99mTc sestamibi associated with breast magnetic resonance imaging for guidance of breast cancer resection. Breast J. 2006; 12(3): 202–207.
  28. Giovanella L, Suriano S, Lunghi L, et al. Radioguided surgery of thyroid carcinoma recurrences: the role of preoperative (99m)Tc-labeled human serum albumin macroaggregates-SPECT/CT mapping. Clin Nucl Med. 2013; 38(4): e207–e209.
  29. Rault E, Vandenberghe S, Van Holen R, et al. Comparison of image quality of different iodine isotopes (I-123, I-124, and I-131). Cancer Biother Radiopharm. 2007; 22(3): 423–430.
  30. Rubello D, Fig LM, Casara D, et al. Italian Study Group on Radiguided Surgery and Immunoscintigraphy (GISCRIS). Radioguided surgery of parathyroid adenomas and recurrent thyroid cancer using the. Cancer Biother Radiopharm. 2006; 21(3): 194–205.
  31. Rubello D, Giannini S, De Carlo E, et al. Minimally invasive (99m)Tc-sestamibi radioguided surgery of parathyroid adenomas. Panminerva Med. 2005; 47(2): 99–107.
  32. van Hulsteijn LT, van der Hiel B, Smit JWA, et al. Intraoperative detection of ganglioneuromas with 123I-MIBG. Clin Nucl Med. 2012; 37(8): 768–771.
  33. Hubalewska-Dydejczyk A, Kulig J, Szybinski P, et al. Radio-guided surgery with the use of [99mTc-EDDA/HYNIC]octreotate in intra-operative detection of neuroendocrine tumours of the gastrointestinal tract. Eur J Nucl Med Mol Imaging. 2007; 34(10): 1545–1555.
  34. Schirmer WJ, O'Dorisio TM, Schirmer TP, et al. Intraoperative localization of neuroendocrine tumors with 125I-TYR(3)-octreotide and a hand-held gamma-detecting probe. Surgery. 1193; 114(4): 745-51; discussion 751-2.
  35. Povoski SP, Neff RL, Mojzisik CM, et al. A comprehensive overview of radioguided surgery using gamma detection probe technology. World J Surg Oncol. 2009; 7: 11.
  36. Gulec SA, Daghighian F, Essner R. PET-Probe: Evaluation of Technical Performance and Clinical Utility of a Handheld High-Energy Gamma Probe in Oncologic Surgery. Ann Surg Oncol. 2016; 23(Suppl 5): 9020–9027.
  37. Hall NC, Povoski SP, Murrey DA, et al. Combined approach of perioperative 18F-FDG PET/CT imaging and intraoperative 18F-FDG handheld gamma probe detection for tumor localization and verification of complete tumor resection in breast cancer. World J Surg Oncol. 2007; 5: 143.
  38. Povoski SP, Hall NC, Martin EW, et al. Multimodality approach of perioperative 18F-FDG PET/CT imaging, intraoperative 18F-FDG handheld gamma probe detection, and intraoperative ultrasound for tumor localization and verification of resection of all sites of hypermetabolic activity in a case of occult recurrent metastatic melanoma. World J Surg Oncol. 2008; 6: 1.
  39. Solfaroli Camillocci E, Schiariti M, Bocci V, et al. First ex vivo validation of a radioguided surgery technique with β-radiation. Phys Med. 2016; 32(9): 1139–1144.
  40. Povoski S, Mojzisik C, Sullivan B. Radioimmunoguided Surgery: Intraoperative Radioimmunodetection for the Radioguided Localization and Resection of Tumors. Radioguided Surgery. 2016: 371–418.
  41. Sun D, Bloomston M, Hinkle G, et al. Radioimmunoguided surgery (RIGS), PET/CT image-guided surgery, and fluorescence image-guided surgery: past, present, and future. J Surg Oncol. 2007; 96(4): 297–308.
  42. Martin E, Mojzisik C, Hinkle G, et al. Radioimmunoguided surgery using monoclonal antibody. The American Journal of Surgery. 1988; 156(5): 386–392.
  43. Mansi L, Cuccurullo V, Ciarmiello A. From Homo sapiens to Homo in nexu (connected man): could functional imaging redefine the brain of a. Eur J Nucl Med Mol Imaging. 2014; 41(7): 1385–1387.
  44. The 2007 Recommendations of the International Commission on Radiological Protection. ICRP publication 103. Ann ICRP. 2007; 37(2-4): 1–332.
  45. Hoyer D, Bell GI, Berelowitz M, et al. Classification and nomenclature of somatostatin receptors. Trends Pharmacol Sci. 1995; 16(3): 86–88.
  46. van der Lely AJ, de Herder WW, Krenning EP, et al. Octreoscan radioreceptor imaging. Endocrine. 2003; 20(3): 307–311.
  47. Shi W, Johnston CF, Buchanan KD, et al. Localization of neuroendocrine tumours with [111In] DTPA-octreotide scintigraphy (Octreoscan): a comparative study with CT and MR imaging. QJM. 1998; 91(4): 295–301.
  48. Adams S, Baum RP, Adams M, et al. [Pre- and intraoperative localization of neuroendocrine tumors]. Acta Med Austriaca. 1997; 24(2): 81–86.
  49. Olsen J, Pozderac R, Hinkle G, et al. Somatostatin receptor imaging of neuroendocrine tumors with indium-111 pentetreotide (Octreoscan). Semin Nucl Med. 1995; 25(3): 251–261.
  50. Kunikowska J, Słodkowski M, Koperski Ł, et al. Radioguided surgery in patient with pancreatic neuroendocrine tumour followed by PET/CT scan as a new approach of complete resection evaluation--case report. Nucl Med Rev Cent East Eur. 2014; 17(2): 110–114.
  51. Akerström G, Makridis C, Johansson H. Abdominal surgery in patients with midgut carcinoid tumors. Acta Oncol. 1991; 30(4): 547–553.
  52. Cuccurullo V, Faggiano A, Scialpi M, et al. Questions and answers: what can be said by diagnostic imaging in neuroendocrine tumors? Minerva Endocrinol. 2012; 37(4): 367–377.
  53. Adams S, Acker P, Lorenz M, et al. Radioisotope-guided surgery in patients with pheochromocytoma and recurrent medullary thyroid carcinoma: a comparison of preoperative and intraoperative tumor localization with histopathologic findings. Cancer. 2001; 92(2): 263–270, doi: 10.1002/1097-0142(20010715)92:2<263::aid-cncr1318>3.0.co;2-z.
  54. Adams S, Baum RP. Intraoperative use of gamma-detecting probes to localize neuroendocrine tumors. Q J Nucl Med. 2000; 44(1): 59–67.
  55. Adams S, Baum RP, Hertel A, et al. Intraoperative gamma probe detection of neuroendocrine tumors. J Nucl Med. 1998; 39(7): 1155–1160.
  56. Adams S, Baum RP, Adams M, et al. [Clinical value of somatostatin receptor scintigraphy. Studies of pre- and intraoperative localization of gastrointestinal and pancreatic tumors]. Med Klin (Munich). 1997; 92(3): 138–143.
  57. Squires MH, Volkan Adsay N, Schuster DM, et al. Octreoscan Versus FDG-PET for Neuroendocrine Tumor Staging: A Biological Approach. Ann Surg Oncol. 2015; 22(7): 2295–2301.
  58. Kaemmerer D, Prasad V, Daffner W, et al. Radioguided surgery in neuroendocrine tumors using Ga-68-labeled somatostatin analogs: a pilot study. Clin Nucl Med. 2012; 37(2): 142–147.
  59. Sadowski SM, Millo C, Neychev V, et al. Feasibility of Radio-Guided Surgery with ⁶⁸Gallium-DOTATATE in Patients with Gastro-Entero-Pancreatic Neuroendocrine Tumors. Ann Surg Oncol. 2015; 22 Suppl 3: S676–S682.
  60. Kitson S, Cuccurullo V, Moody T, et al. Radionuclide Antibody-Conjugates, a Targeted Therapy Towards Cancer. Current Radiopharmaceuticals. 2013; 6(2): 57–71.
  61. Buchmann I, Henze M, Engelbrecht S, et al. Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2007; 34(10): 1617–1626.
  62. Hodolic M, Fettich J, Marzola MC, et al. Radioguided surgery and systemic radionuclide therapy of neuroendocrine tumours. In Vivo. 2010; 24(1): 97–100.
  63. Gulec SA, Baum R. Radio-guided surgery in neuroendocrine tumors. J Surg Oncol. 2007; 96(4): 309–315.
  64. Mansi L, Rambaldi PF, Panza N, et al. Diagnosis and radioguided surgery with 111In-pentetreotide in a patient with paraneoplastic Cushing's syndrome due to a bronchial carcinoid. Eur J Endocrinol. 1997; 137(6): 688–690.
  65. Santini M, Rambaldi PF, Di Lieto E, et al. [Role of radio-guided surgery with 111In-octreotide in the treatment of thoracic neoplasms]. Minerva Endocrinol. 2001; 26(4): 285–288.
  66. Cascini GL, Cuccurullo V, Tamburrini O, et al. Peptide imaging with somatostatin analogues: more than cancer probes. Curr Radiopharm. 2013; 6(1): 36–40.
  67. Bhanot Y, Rao S, Parmeshwaran RV. Radio-guided neurosurgery (RGNS): early experience with its use in brain tumour surgery. Br J Neurosurg. 2007; 21(4): 382–388.
  68. Kiviniemi A, Gardberg M, Frantzén J, et al. Somatostatin receptor subtype 2 in high-grade gliomas: PET/CT with (68)Ga-DOTA-peptides, correlation to prognostic markers, and implications for targeted radiotherapy. EJNMMI Res. 2015; 5: 25.
  69. Gay E, Vuillez JP, Palombi O, et al. Intraoperative and postoperative gamma detection of somatostatin receptors in bone-invasive en plaque meningiomas. Neurosurgery. 2005; 57(1 Suppl): 107-113; discussion 107-113.
  70. Chamberlain MC, Glantz MJ, Fadul CE. Recurrent meningioma: salvage therapy with long-acting somatostatin analogue. Neurology. 2007; 69(10): 969–973.
  71. Seystahl K, Stoecklein V, Schüller U, et al. Somatostatin receptor-targeted radionuclide therapy for progressive meningioma: benefit linked to 68Ga-DOTATATE/-TOC uptake. Neuro-oncology. 2016; 18(11): 1538–1547.
  72. Simó M, Argyriou AA, Macià M, et al. Recurrent high-grade meningioma: a phase II trial with somatostatin analogue therapy. Cancer Chemother Pharmacol. 2014; 73(5): 919–923.
  73. Heute D, Kostron H, von Guggenberg E, et al. Response of recurrent high-grade glioma to treatment with (90)Y-DOTATOC. J Nucl Med. 2010; 51(3): 397–400.
  74. Schaer JC, Waser B, Mengod G, et al. Somatostatin receptor subtypes sst1, sst2, sst3 and sst5 expression in human pituitary, gastroentero-pancreatic and mammary tumors: comparison of mRNA analysis with receptor autoradiography. Int J Cancer. 1997; 70(5): 530–537, doi: 10.1002/(sici)1097-0215(19970304)70:5<530::aid-ijc7>3.3.co;2-f.
  75. Kumar U, Grigorakis SI, Watt HL, et al. Somatostatin receptors in primary human breast cancer: quantitative analysis of mRNA for subtypes 1--5 and correlation with receptor protein expression and tumor pathology. Breast Cancer Res Treat. 2005; 92(2): 175–186.
  76. van Eijck CH, Krenning EP, Bootsma A, et al. Somatostatin-receptor scintigraphy in primary breast cancer. Lancet. 1994; 343(8898): 640–643.
  77. Vural G, Unlü M, Atasever T, et al. Comparison of indium-111 octreotide and thallium-201 scintigraphy in patients mammographically suspected of having breast cancer: preliminary results. Eur J Nucl Med. 1997; 24(3): 312–315.
  78. Chiti A, Agresti R, Maffioli LS, et al. Breast cancer staging using technetium-99m sestamibi and indium-111 pentetreotide single-photon emission tomography. Eur J Nucl Med. 1997; 24(2): 192–196.
  79. Albérini JL, Meunier B, Denzler B, et al. Somatostatin receptor in breast cancer and axillary nodes: study with scintigraphy, histopathology and receptor autoradiography. Breast Cancer Res Treat. 2000; 61(1): 21–32.
  80. Mezi S, Primi F, Orsi E, et al. Somatostatin receptor scintigraphy in metastatic breast cancer patients. Oncol Rep. 2005; 13(1): 31–35.
  81. Huang CM, Wu YT, Chen ST. Targeting delivery of paclitaxel into tumor cells via somatostatin receptor endocytosis. Chem Biol. 2000; 7(7): 453–461.
  82. Sharma K, Srikant CB. Induction of wild-type p53, Bax, and acidic endonuclease during somatostatin-signaled apoptosis in MCF-7 human breast cancer cells. Int J Cancer. 1998; 76(2): 259–266, doi: 10.1002/(sici)1097-0215(19980413)76:2<259::aid-ijc14>3.0.co;2-7.
  83. Bontenbal M, Foekens JA, Lamberts SW, et al. Feasibility, endocrine and anti-tumour effects of a triple endocrine therapy with tamoxifen, a somatostatin analogue and an antiprolactin in post-menopausal metastatic breast cancer: a randomized study with long-term follow-up. Br J Cancer. 1998; 77(1): 115–122.
  84. Bajetta E, Procopio G, Ferrari L, et al. A randomized, multicenter prospective trial assessing long-acting release octreotide pamoate plus tamoxifen as a first line therapy for advanced breast carcinoma. Cancer. 2002; 94(2): 299–304.
  85. Pilichowska M, Kimura N, Schindler M, et al. Expression of somatostatin type 2A receptor correlates with estrogen receptor in human breast carcinoma. Endocr Pathol. 2000; 11(1): 57–67.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., Świętokrzyska 73 street, 80–180 Gdańsk, Poland

phone: +48 58 320 94 94, fax: +48 58 320 94 60, e-mail: viamedica@viamedica.pl