Targeting personalized medicine in a non-Hodgkin lymphoma patient with 18F-FDG and 18F-choline PET/CT

Thalles H. Ribeiro Raul S. Filho Ana Carolina G. Castro Eduardo Paulino Jr Marcelo Mamede About the authors

Summary

Early diagnosis and staging of non-Hodgkin lymphoma (NHL) is essential for therapeutic strategy decision. Positron emission tomography/computed tomography (PET/CT) with fluordeoxyglucose (FDG), a glucose analogue, labeled with fluor-18 (18F-FDG) has been used to evaluate staging, therapy response and prognosis in NHL patients. However, in some cases, 18F-FDG has shown false-positive uptake due to inflammatory reaction after chemo and/or radiation therapy. In this case report, we present a NHL patient evaluated with 18F-FDG and 18F-choline PET/CT scan imaging pre- and post-therapy. 18F-FDG and 18F-choline PET/CT were performed for the purpose of tumor staging and have shown intense uptake in infiltrative tissue as well as in the lymph node, but with some mismatching in the tumor. Post-treatment 18F-FDG and 18F-choline PET/ CT scans revealed no signs of radiotracer uptake, suggesting complete remission of the tumor. 18F-choline may be a complimentary tool for staging and assessment of therapeutic response in non-Hodgkin lymphoma, while non-18F-FDG tracer can be used for targeted therapy and patient management.

Keywords:
18F-FDG; 18F-choline; PET/CT; non-Hodgkin lymphoma; neoplasm staging

Early diagnosis and staging of non-Hodgkin lymphoma (NHL) is an essential process that involves many different technologies.11 Regacini R, Puchnick A, Shigueoka DC, Iared W, Lederman HM. Whole-body diffusion-weighted magnetic resonance imaging versus FDG-PET/CT for initial lymphoma staging: systematic review on diagnostic test accuracy studies. São Paulo Med J. 2015; 133(2):141-50. Hybrid positron emission tomography/ computed tomography (PET/CT) with fluordeoxyglucose (FDG), a glucose analogue, labeled with fluor-18 (18F-FDG) has been largely used to evaluate staging, therapy response and prognosis in NHL patients.22 Spaccarelli N, Gharavi M, Saboury B, Cheng G, Rook AH, Alavi A. Role of (18) F-fluorodeoxyglucose positron emission tomography imaging in the management of primary cutaneous lymphomas. Hell J Nucl Med. 2014; 17(2):78-84.,33 Metser U, Hussey D, Murphy G. Impact of 18F-FDG PET/CT on the staging and management of follicular lymphoma. Br J Radiol. 2014; 87(1042):20140360. PET/CT combines morphological and metabolic information of the cancerous tissue, providing more accurate data regarding its different behaviors.22 Spaccarelli N, Gharavi M, Saboury B, Cheng G, Rook AH, Alavi A. Role of (18) F-fluorodeoxyglucose positron emission tomography imaging in the management of primary cutaneous lymphomas. Hell J Nucl Med. 2014; 17(2):78-84.,33 Metser U, Hussey D, Murphy G. Impact of 18F-FDG PET/CT on the staging and management of follicular lymphoma. Br J Radiol. 2014; 87(1042):20140360.,44 Dai Y, Sowjanya M, You J, Xu K. Non Hodgkin's lymphoma of multiple skeletal muscles involvement seen on FDG PET/CT scans. Medicine (Baltimore). 2015; 94(18):e833. However, in some cases, 18F-FDG has shown false-positive uptake due to inflammatory reaction after chemo and/or radiation therapy.55 Kong F-L, Ford RJ, Yang DJ. Managing lymphoma with non-FDG radiotracers: current clinical and preclinical applications. Biomed Res Int. 2013; 2013:626910.,66 Avivi I, Zilberlicht A, Dann EJ, Leiba R, Faibish T, Rowe JM, et al. Strikingly high false positivity of surveillance FDG-PET/CT scanning among patients with diffuse large cell lymphoma in the rituximab era. Am J Hematol. 2013; 88(5):400-5. In order to overcome this problem and increase the accuracy of malignant cell detection, especially to assess response to different therapeutic modalities, non-18F-FDG PET radiotracers might be an interesting strategy. Thus, in this study, we present the case of a patient diagnosed with NHL assessed through PET/CT scan imaging using 18F-FDG and 18F-choline pre- and post-chemoradiation therapy, in order to determine and improve specific patient management.

A 61-year-old male patient, in good general condition at physical examination, presented an irregular ulcerated lesion in the anterior chest wall. 18F-FDG PET/CT imaging, performed for staging, showed intense uptake in infiltrative tissue into pectoral muscles reaching the sternal body with involvement of supra- and infradiaphragmatic lymph nodes (Figure 1A and E). Further pre-therapy, 18F-choline PET/CT scans were consistent with increased radiotracer uptake in the lesion site as well as in the lymph nodes (Figure 1B and F), but with some mismatching in the tumor (Figure 1F). Histological and immunohistochemistry examinations revealed areas of dense and diffuse infiltrate of large anaplastic cells with strong positivity for CD20 and CD10, and a high proliferative profile with strong and diffuse positivity for Ki-67, that corroborate with the diagnosis of cutaneous large-B cells non-Hodgkin lymphoma (NHL) (Figure 1G and H). The patient was then referred for oncological treatment, thus receiving eight cycles of lymphoma standard (R-chop) chemotherapy followed by conformational radiotherapy (30,6 Gy) in the lesion site. Six weeks after chemoradiotherapy, post-treatment 18F-FGD and 18F-choline PET/CT scans were again performed and revealed no signs of radiotracer uptake, suggesting complete remission of the tumor (Figure 1C and D). Remission was confirmed in sixteen-month follow up with conventional imaging (CT).

FIGURE 1
A 61-year-old man diagnosed with sternal cutaneous large B-cell non-Hodgkin lymphoma (NHL) (Panel G) underwent PET/CT scans pre- and post-therapy for tumor staging and assessment of response to treatment, respectively, using 18F-FDG and 18F-choline. The 18F-FDG uptake (A and E) showed intense metabolic activity in areas of the tumor with high proliferative pattern (Panel H - strong and diffuse positivity for Ki-67). However, the uptake of 18F-choline (B and F) was more intense in areas of lower glucose consumption of the tumor (arrow).

18F-FDG PET/CT imaging is a well-established imaging technique in clinical oncology.77 Coughlan M, Elstrom R. The use of FDG-PET in diffuse large B cell lymphoma (DLBCL): predicting outcome following first line therapy. Cancer Imaging. 2014; 14(1):34. One of the advantages of using this radiotracer is that it targets glucose phosphorylation, which is increased in malignant tumors due to overexpression of glucose membrane transporters and high glycolytic rate, creating positive tumor to back-ground images.88 Ansell SM, Armitage JO. Positron emission tomographic scans in lymphoma: convention and controversy. Mayo Clinic Proc. 2012; 87(6):571-80. Although it is considered as highly sensitive in tumor detection, current data indicate that the number of false positive images obtained from 18F-FDG PET/CT is pointed as its most important limitation.99 Lind P, Igerc I, Beyer T, Reinprecht P, Hausegger K. Advantages and limitations of FDG PET in the follow-up of breast cancer. Eur J Nucl Med Mol Imaging. 2004; 31(Suppl 1):S125-34.

As a non-specific radiotracer for malignant cells, the limitation of the test is based on the fact that 18F-FDG uptake may be shown in areas with no carcinogenic behavior. Thereby, inflammation reaction (common in cancerous tissues), brown adipose tissue or even benign cell proliferation can create positive images, more likely to be misinterpreted as malignant cell proliferations.99 Lind P, Igerc I, Beyer T, Reinprecht P, Hausegger K. Advantages and limitations of FDG PET in the follow-up of breast cancer. Eur J Nucl Med Mol Imaging. 2004; 31(Suppl 1):S125-34.,1010 Zhuang H, Pourdehnad M, Lambright ES, Yamamoto AJ, Lanuti M, Li P, et al. Dual time point 18F-FDG PET imaging for differentiating malignant from inflammatory processes. J Nucl Med. 2001; 42(9):1412-7. A second significant limitation of this method relies on the fibrotic areas in post-therapy healing tissue to take up the radioactive glucose analogue even in cases of complete tumor remission, hence limiting treatment evaluation.1111 Qiu L, Chen Y, Wu J. The role of 18F-FDG PET and 18F-FDG PET/CT in the evaluation of pediatric Hodgkin's lymphoma and non-Hodgkin's lymphoma. Hell J Nucl Med. 2013; 16(3):230-6.

As a complementary analysis, 18F-choline PET/CT scans were obtained from a patient aiming to create more solid data regarding tumor profile, even though it is most commonly used in management of patients diagnosed with prostate cancer.1212 Hodolic M. Role of (18) F-choline PET/CT in evaluation of patients with prostate carcinoma. Radiol Oncol. 2011; 45(1):17-21. A previously published paper describes overexpression of choline kinase1212 Hodolic M. Role of (18) F-choline PET/CT in evaluation of patients with prostate carcinoma. Radiol Oncol. 2011; 45(1):17-21. in malignant cells, an enzyme responsible for phosphorylating choline into phosphatidylcholine, initiating the synthesis of cell membrane phospholipids.1212 Hodolic M. Role of (18) F-choline PET/CT in evaluation of patients with prostate carcinoma. Radiol Oncol. 2011; 45(1):17-21.,1313 Vali R, Loidl W, Pirich C, Langesteger W, Beheshti M. Imaging of prostate cancer with PET/CT using 18F-Fluorocholine. Am J Nucl Med Mol Imag. 2015; 5(2):96-108. Thereby, positive images are shown in response to increased cell proliferation in the lesion area, where more membrane formation is observed.1414 Kitajima K, Murphy RC, Nathan MA, Sugimura K. Update on positron emission tomography for imaging of prostate cancer. Int J Urol. 2014; 21(1):12-23.,1515 Kitajima K, Murphy RC, Nathan, MA. Choline PET/CT for imaging prostate cancer: an update. Ann Nucl Med. 2013; 27(7):581-91.

Axial views obtained with 18F-FDG and 18F-choline PET/CT scanning show different radiotracer uptake in the same region of the tumor, possibly meaning diverse cell differentiation. Areas of intense 18F-FDG revealed low 18F-choline uptake, and vice-versa, revealing a mismatch of metabolic and molecular biology of tumor behavior. On the other hand, both radiotracers were capable to evaluate response to chemoradiation therapy, confirmed with a long follow-up period.

18F-FDG PET/CT scan is a valuable and established technique in NHL patient management. However, 18F-choline can be a complimentary tool for tumor staging and assessment of therapeutic response in non-Hodgkin lymphoma. The images obtained in this study showing differential radiotracer uptake by cancer cells in distinct parts of the tumor depict differential metabolic behavior in the lesion. Non-18F-FDG tracer can be used for targeted therapy and patient management.

  • Study conducted at Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil

Acknowledgments

The authors thank CNPq and FAPEMIG for financial support and Sofia Lage for text proofreading.

References

  • 1
    Regacini R, Puchnick A, Shigueoka DC, Iared W, Lederman HM. Whole-body diffusion-weighted magnetic resonance imaging versus FDG-PET/CT for initial lymphoma staging: systematic review on diagnostic test accuracy studies. São Paulo Med J. 2015; 133(2):141-50.
  • 2
    Spaccarelli N, Gharavi M, Saboury B, Cheng G, Rook AH, Alavi A. Role of (18) F-fluorodeoxyglucose positron emission tomography imaging in the management of primary cutaneous lymphomas. Hell J Nucl Med. 2014; 17(2):78-84.
  • 3
    Metser U, Hussey D, Murphy G. Impact of 18F-FDG PET/CT on the staging and management of follicular lymphoma. Br J Radiol. 2014; 87(1042):20140360.
  • 4
    Dai Y, Sowjanya M, You J, Xu K. Non Hodgkin's lymphoma of multiple skeletal muscles involvement seen on FDG PET/CT scans. Medicine (Baltimore). 2015; 94(18):e833.
  • 5
    Kong F-L, Ford RJ, Yang DJ. Managing lymphoma with non-FDG radiotracers: current clinical and preclinical applications. Biomed Res Int. 2013; 2013:626910.
  • 6
    Avivi I, Zilberlicht A, Dann EJ, Leiba R, Faibish T, Rowe JM, et al. Strikingly high false positivity of surveillance FDG-PET/CT scanning among patients with diffuse large cell lymphoma in the rituximab era. Am J Hematol. 2013; 88(5):400-5.
  • 7
    Coughlan M, Elstrom R. The use of FDG-PET in diffuse large B cell lymphoma (DLBCL): predicting outcome following first line therapy. Cancer Imaging. 2014; 14(1):34.
  • 8
    Ansell SM, Armitage JO. Positron emission tomographic scans in lymphoma: convention and controversy. Mayo Clinic Proc. 2012; 87(6):571-80.
  • 9
    Lind P, Igerc I, Beyer T, Reinprecht P, Hausegger K. Advantages and limitations of FDG PET in the follow-up of breast cancer. Eur J Nucl Med Mol Imaging. 2004; 31(Suppl 1):S125-34.
  • 10
    Zhuang H, Pourdehnad M, Lambright ES, Yamamoto AJ, Lanuti M, Li P, et al. Dual time point 18F-FDG PET imaging for differentiating malignant from inflammatory processes. J Nucl Med. 2001; 42(9):1412-7.
  • 11
    Qiu L, Chen Y, Wu J. The role of 18F-FDG PET and 18F-FDG PET/CT in the evaluation of pediatric Hodgkin's lymphoma and non-Hodgkin's lymphoma. Hell J Nucl Med. 2013; 16(3):230-6.
  • 12
    Hodolic M. Role of (18) F-choline PET/CT in evaluation of patients with prostate carcinoma. Radiol Oncol. 2011; 45(1):17-21.
  • 13
    Vali R, Loidl W, Pirich C, Langesteger W, Beheshti M. Imaging of prostate cancer with PET/CT using 18F-Fluorocholine. Am J Nucl Med Mol Imag. 2015; 5(2):96-108.
  • 14
    Kitajima K, Murphy RC, Nathan MA, Sugimura K. Update on positron emission tomography for imaging of prostate cancer. Int J Urol. 2014; 21(1):12-23.
  • 15
    Kitajima K, Murphy RC, Nathan, MA. Choline PET/CT for imaging prostate cancer: an update. Ann Nucl Med. 2013; 27(7):581-91.

Publication Dates

  • Publication in this collection
    Feb 2017

History

  • Received
    18 May 2016
  • Accepted
    19 May 2016
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