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68Ga-DOTANOC PET/CT for Screening and Surveillance of Von Hippel-Lindau (VHL) disease

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Abstract

Purpose

Hereditary tumor syndrome Von Hippel-Lindau (VHL) disease is characterized by various benign and malignant tumors that are known to express somatostatin receptors (SSTR). We evaluated the role of 68Ga-DOTANOC PET/CT scan in patients with positive germline mutation of the VHL gene, presented initially or on follow-up, for the detection of recurrent or synchronous/metachronous lesions.

Methods

Fourteen patients (8 males; 6 females) with mean age 30 ± 9.86 years were retrospectively analyzed, were tested positive for VHL on gene dosage analysis, and underwent 68 Ga-DOTANOC PET/CT scan for disease evaluation. The number and site of lesions were determined. The tracer uptake was analyzed semi-quantitatively by calculating the maximum standardized uptake values (SUVmax) of lesion.

Results

Four of the 14 patients underwent scan for initial diagnosis as baseline, 6 patients for post-therapy disease status, and 4 patients for initial diagnosis as well as follow-up evaluation of the disease. A total of 67 lesions were detected in 14 patients. The sites of lesions were cerebellar/vertebral/spinal (17; mean SUVmax = 7.85); pancreatic neuroendocrine tumor (NET) (11; mean SUVmax = 20.64); retina (3; mean SUVmax = 10.46); pheochromocytoma (10; mean SUVmax = 16.32); paragangliomas (3; mean SUVmax = 10.65); pancreatic cyst (9; mean SUVmax = 2.54); and renal cyst (8; mean SUVmax = 1.56) and miscellaneous lesions constituted 6 lesions.

Conclusion

Our results show that 68 Ga-DOTANOC PET/CT may be a useful modality for screening and follow-up of associated tumors in patients with germline gene mutation for VHL. It can be used as a one-stop imaging modality for VHL patients and may substitute for separate radiological investigations, making it more convenient for patients in terms of time and cost.

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Data Availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Lonser RR, Glenn GM, Walther M, Chew EY, Libutti SK, Linehan WM, et al. von Hippel-Lindau disease. Lancet. 2003;361:2059–67.

    Article  CAS  PubMed  Google Scholar 

  2. Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993;260:1317–20.

    Article  CAS  PubMed  Google Scholar 

  3. Maher ER. Von Hippel-Lindau disease. Eur J Cancer. 1994;30:1987–90.

    Article  Google Scholar 

  4. Maher ER, Yates JR, Harries R, Benjamin C, Harris R, Moore AT, et al. Clinical features and natural history of von Hippel-Lindau disease. QJM. 1990;77:1151–63.

    Article  CAS  PubMed  Google Scholar 

  5. Neumann HPH, Wiestler OD. Clustering of features of von Hippel-Lindau syndrome: evidence for a complex genetic locus. Lancet. 1991;337:1052–4.

    Article  CAS  PubMed  Google Scholar 

  6. Varshney N, Kebede AA, Owusu-Dapaah H, Lather J, Kaushik M, Bhullar JS. A review of Von Hippel-Lindau syndrome. J Kidney Cancer VHL. 2017;4:20–9.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Chittiboina P, Lonser RR. Von Hippel–Lindau disease. In: M.P. Islam and E.S. Roach, editors. Handbook of clinical neurology: neurocutaneous syndromes; 2015; 132 (3): pp. 139–56.

  8. Shell J, Tirosh A, Millo C, Sadowski SM, Assadipour Y, Green P, et al. The utility of 68Gallium-DOTATATE PET/CT in the detection of von Hippel- T Lindau disease associated tumors. European J Radiology. 2019;112:130–5.

    Article  Google Scholar 

  9. Sharma P, Dhull VS, Bal CS, Malhotra A, Kumar R. Von Hippel-Lindau syndrome: demonstration of entire disease spectrum with 68Ga-DOTANOC PET-CT. Korean J Radiol. 2014;15:169–72.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Sizdahkhani S, Feldman MJ, Piazza MG, Ksendzovsky A, Edwards NA, Ray Chaudhury A, et al. Somatostatin receptor expression on von Hippel-Lindau-associated hemangioblastomas offers novel therapeutic target. Sci Rep. 2017;7:40822. https://doi.org/10.1038/srep40822.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ambrosini V, Campana D, Allegri V, Opocher G, Fanti S. 68Ga-DOTA-NOC PET/CT detects somatostatin receptors expression in von Hippel-Lindau cerebellar disease. Clin Nucl Med. 2011;36:64–5.

    Article  PubMed  Google Scholar 

  12. Papadakis GZ, Millo C, Jassel IS, Bagci U, Sadowski SM, Karantanas AH, et al. 18F-FDG and 68Ga-DOTATATE PET/CT in von Hippel-Lindau disease–associated retinal hemangioblastoma. Clin Nucl Med. 2017;42:189–90.

    Article  PubMed  Google Scholar 

  13. Papadakis GZ, Millo C, Sadowski SM, Bagci U, Patronas NJ. Endolymphatic sac tumor showing increased activity on 68Ga DOTATATE PET/CT. Clin Nucl Med. 2016;41:783–4.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Papadakis GZ, Millo C, Sadowski SM, Bagci U, Patronas NJ. Epididymal cystadenomas in von Hippel-Lindau disease showing increased activity on 68Ga DOTATATE PET/CT. Clin Nucl Med. 2016;41:781–2.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Papadakis GZ, Millo C, Sadowski SM, Bagci U, Patronas NJ. Kidney tumor in a von Hippel-Lindau (VHL) patient with intensely increased activity on 68Ga-DOTA-TATE PET/CT. Clin Nucl Med. 2016;41:970–1.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Prasad V, Tiling N, Denecke T, Brenner W, Plöckinger U. Potential role of 68Ga-DOTATOC PET/CT in screening for pancreatic neuroendocrine tumour in patients with von Hippel-Lindau disease. Eur J Nucl Med Mol Imaging. 2016;43:2014–20.

    Article  CAS  PubMed  Google Scholar 

  17. Hes FJ, van der Luijt RB, Lips CJ. Clinical management of Von Hippel-Lindau (VHL) disease. Neth J Med. 2001;59:225–34.

    Article  CAS  PubMed  Google Scholar 

  18. Lammens CR, Aaronson NK, Hes FJ, Links TP, Zonnenberg BA, Lenders JW, et al. Compliance with periodic surveillance for Von-Hippel-Lindau disease. Genet Med. 2011;13:519–27.

    Article  PubMed  Google Scholar 

  19. Poulsen M, Budtz-Jorgensen E, Bisgaard M. Surveillance in von Hippel-Lindau disease (VHL). Clin Genet. 2010;77:49–59.

    Article  CAS  PubMed  Google Scholar 

  20. VHL Family Alliance. The VHL Handbook: what you need to know about VHL. In: The VHL Alliance. 6th edition; revised 2020: pp. 14–15.

  21. Ilhan H, Fendler WP, Cyran CC, Spitzweg C, Auernhammer CJ, Gildehaus FJ, et al. Impact of 68Ga-DOTATATE PET/CT on the surgical management of primary neuroendocrine tumors of the pancreas or ileum. Ann Surg Oncol. 2015;22:164–71.

    Article  PubMed  Google Scholar 

  22. Haug AR, Cindea-Drimus R, Auernhammer CJ, Reincke M, Wängler B, Uebleis C, et al. The role of 68Ga-DOTATATE PET/CT in suspected neuroendocrine tumors. J Nucl Med. 2012;53:1686–92.

    Article  CAS  PubMed  Google Scholar 

  23. Mojtahedi A, Thamake S, Tworowska I, Ranganathan D, Delpassand ES. The value of (68)Ga-DOTATATE PET/CT in diagnosis and management of neuroendocrine tumors compared to current FDA approved imaging modalities: a review of literature. Am J Nucl Med Mol Imaging. 2014;4:426–34.

    PubMed  PubMed Central  Google Scholar 

  24. Hofman MS, Kong G, Neels OC, Eu P, Hong E, Hicks RJ. High management impact of Ga-68 DOTATATE (GaTate) PET/CT for imaging neuroendocrine and other somatostatin expressing tumours: management impact of GaTate PET/CT. J Med Imaging Radiat Oncol. 2012;56:40–7.

    Article  PubMed  Google Scholar 

  25. Schmid-Tannwald C, Schmid-Tannwald CM, Morelli JN, Neumann R, Haug AR, Jansen N, et al. Comparison of abdominal MRI with diffusion-weighted imaging to 68Ga-DOTATATE PET/CT in detection of neuroendocrine tumors of the pancreas. Eur J Nucl Med Mol Imaging. 2013;40:897–907.

    Article  CAS  PubMed  Google Scholar 

  26. Sadowski SM, Neychev V, Millo C, Shih J, Nilubol N, Herscovitch P, et al. Prospective study of 68 Ga-DOTATATE positron emission tomography/computed tomography for detecting gastro-entero-pancreatic neuroendocrine tumors and unknown primary sites. J Clin Oncol. 2016;34(6):588–96.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Nuclear Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India

    Shamim Ahmed Shamim, Geetanjali Arora, Naresh Kumar, Jhangir Hussain, Shreya Datta Gupta, Arun Raj ST, Kritin Shankar, Sambit Sagar & Chandrasekhar Bal

  2. Department of Endocrinology, Metabolism & Diabetes, All India Institute of Medical Sciences (AIIMS), New Delhi, India

    Alpesh Goyal & Rajesh Khadgawat

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  1. Shamim Ahmed Shamim
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Contributions

In this study, 11 authors have made their contributions and we hereby certify that there is a significant contribution by all the authors in the study as given below:

Shamim Ahmed Shamim (corresponding author): conception and design of study, data interpretation, and writing the manuscript.

Geetanjali Arora: analysis of data, data interpretation, and writing the manuscript.

Naresh Kumar: data collection; data compilation, writing and revising the manuscript.

Jhangir Hussain: collection and compilation of data.

Shreya Datta Gupta: data interpretation and writing the manuscript.

Arun Raj ST: data interpretation.

Kritin Shankar: writing the manuscript.

Alpesh Goyal: data interpretation and clinical correlation of image findings.

Rajesh Khadgawat: conception and design of study.

Sambit Sagar: writing the manuscript.

Chandrasekhar Bal: conception and design of study.

Corresponding author

Correspondence to Shamim Ahmed Shamim.

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Conflict of Interest

Shamim Ahmed Shamim, Geetanjali Arora, Naresh Kumar, Jhangir Hussain, Shreya Datta Gupta, Arun Raj ST, Kritin Shankar, Alpesh Goyal, Rajesh Khadgawat, Sambit Sagar, and Chandrasekhar Bal declare no conflict of interest.

Ethical Statement

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of All India Institute of Medical Sciences, New Delhi, India.

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Informed consent was obtained from all individual participants included in the study.

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Shamim, S.A., Arora, G., Kumar, N. et al. 68Ga-DOTANOC PET/CT for Screening and Surveillance of Von Hippel-Lindau (VHL) disease. Nucl Med Mol Imaging 57, 235–242 (2023). https://doi.org/10.1007/s13139-023-00810-9

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