Top

Published in:

Open Access 01-12-2018 | Research article

Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [¹⁸F]FDG and sodium [¹⁸F]fluoride PET

Authors: María Collantes, Naiara Martínez-Vélez, Marta Zalacain, Lucia Marrodán, Margarita Ecay, María José García-Velloso, Marta María Alonso, Ana Patiño-García, Iván Peñuelas

Published in: BMC Cancer | Issue 1/2018

Abstract

Background

Osteosarcoma is the most common malignant bone tumor in children and young adults that produces aberrant osteoid. The aim of this study was to assess the utility of 2-deoxy-2-[18F-] fluoro-D-glucose ([¹⁸F] FDG) and sodium [¹⁸F] Fluoride (Na [¹⁸F] F) PET scans in orthotopic murine models of osteosarcoma to describe the metabolic pattern of the tumors, to detect and diagnose tumors and to evaluate the efficacy of a new treatment based in oncolytic adenoviruses.

Methods

Orthotopic osteosarcoma murine models were created by the injection of 143B and 531MII cell lines. [¹⁸F]FDG and Na [¹⁸F] F PET scans were performed 30 days (143B) and 90 days (531MII) post-injection. The antitumor effect of two doses (10⁷ and 10⁸ pfu) of the oncolytic adenovirus VCN-01 was evaluated in 531 MII model by [¹⁸F] FDG PET studies. [¹⁸F] FDG uptake was quantified by SUVmax and Total Lesion Glycolysis (TLG) indexes. For Na [¹⁸F] F, the ratio tumor SUVmax/hip SUVmax was calculated. PET findings were confirmed by histopathological techniques.

Results

The metabolic pattern of tumors was different between both orthotopic models. All tumors showed [¹⁸F] FDG uptake, with a sensitivity and specificity of 100%. The [¹⁸F] FDG uptake was significantly higher for the 143B model (p < 0.001). Sensitivity for Na [¹⁸F] F was around 70% in both models, with a specificity of 100%. 531MII tumors showed a heterogeneous Na [¹⁸F] F uptake, significantly higher than 143B tumors (p < 0.01). Importantly, [¹⁸F] FDG and Na [¹⁸F] F uptake corresponded to highly cellular or osteoid-rich tumors in the histopathological analysis, respectively. [¹⁸F] FDG data confirmed that the oncolytic treatment of 531MII tumors produced a significant reduction in growth even with the 10⁷ pfu dose.

Conclusions

PET studies demonstrated that the different osteosarcoma xenograft models developed tumors with diverse metabolic patterns that can be described by multitracer PET studies. Since not all tumors produced abundant osteoid, [¹⁸F] FDG demonstrated a better sensitivity for tumor detection and was able to quantitatively monitor in vivo response to the oncolytic adenovirus VCN-01.

Available only for authorised users

Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. In: Pediatric and adolescent osteosarcoma. New York: Springer; 2009. p. 3–13.CrossRef

Luetke A, Meyers PA, Lewis I, Juergens H. Osteosarcoma treatment - where do we stand? A state of the art review. Cancer Treat Rev. 2014;40:523–32.CrossRef

Gill J, Ahluwalia MK, Geller D, Gorlick R. New targets and approaches in osteosarcoma. Pharmacol Ther. 2013;137:89–99.CrossRef

Brenner W, Bohuslavizki KH. Eary JF. PET imaging of osteosarcoma. J Nucl Med. 2003;44:930–42.PubMed

Angelini A, Ceci F, Castellucci P, Graziani T, Polverari G, Trovarelli G, et al. The role of 18F-FDG PET/CT in the detection of osteosarcoma recurrence. Eur J Nucl Med Mol Imaging. 2017;44:1712–20. https://doi.org/10.1007/s00259-017-3698-0.CrossRefPubMed

Byun BH, Kong C-B, Lim I, Il KB, Choi CW, Song WS, et al. Comparison of (18) F-FDG PET/CT and (99 m) Tc-MDP bone scintigraphy for detection of bone metastasis in osteosarcoma. Skelet Radiol. 2013;42:1673–81. https://doi.org/10.1007/s00256-013-1714-4.CrossRef

Benz MR, Czernin J, Allen-Auerbach MS, Tap WD, Dry SM, Elashoff D, et al. FDG-PET/CT imaging predicts histopathologic treatment responses after the initial cycle of neoadjuvant chemotherapy in high-grade soft-tissue sarcomas. Clin Cancer Res. 2009;15:2856–63.CrossRef

Byun BH, Kong C-B, Lim I, Il KB, Choi CW, Song WS, et al. Early response monitoring to neoadjuvant chemotherapy in osteosarcoma using sequential 18 F-FDG PET/CT and MRI. Eur J Nucl Med Mol Imaging. 2014;41:1553–62. https://doi.org/10.1007/s00259-014-2746-2.CrossRefPubMed

Li Y, Schiepers C, Lake R, Dadparvar S, Berenji GR. Clinical utility of (18) F-fluoride PET/CT in benign and malignant bone diseases. Bone. 2012;50:128–39. https://doi.org/10.1016/j.bone.2011.09.053. CrossRefPubMed

10.

Campanile C, Arlt MJ, Kramer SD, Honer M, Gvozdenovic A, Brennecke P, et al. Characterization of different osteosarcoma phenotypes by PET imaging in preclinical animal models. J Nucl Med. 2013;54:1362–8.CrossRef

11.

Broadhead ML, Lokmic Z, Tan ML, Stevenson A, Binns DS, Cullinane C, et al. Applying advanced imaging techniques to a murine model of Orthotopic osteosarcoma. Front Surg. 2015;2:36.CrossRef

12.

Collantes M, Martinez-Velez N, Zalacain M, Marrodan L, Ecay M, Garcia-Velloso M, et al. Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by 18F-FDG and 18F-fluoride PET. European Association of Nuclear Medicine. Eur J Nucl Med Mol Imaging. 2018;41(2):S251.

13.

Hricak H. Oncologic imaging: a guiding hand of personalized cancer care. Radiology. 2011;259:633–40.CrossRef

14.

Amin S, Bathe OF. Response biomarkers: re-envisioning the approach to tailoring drug therapy for cancer. BMC Cancer. 2016;16:850. https://doi.org/10.1186/s12885-016-2886-9.CrossRefPubMedPubMedCentral

15.

Martinez-Velez N, Xipell E, Vera B, Acanda de la Rocha A, Zalacain M, Marrodan L, et al. The Oncolytic adenovirus VCN-01 as therapeutic approach against pediatric osteosarcoma. Clin Cancer Res. 2016;22:2217–25.CrossRef

16.

Patino-Garcia A, Zalacain M, Folio C, Zandueta C, Sierrasesumaga L, San Julian M, et al. Profiling of chemonaive osteosarcoma and paired-normal cells identifies EBF2 as a mediator of osteoprotegerin inhibition to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis. Clin Cancer Res. 2009;15:5082–91.CrossRef

17.

Fueyo J, Alemany R, Gomez-Manzano C, Fuller GN, Khan A, Conrad CA, et al. Preclinical characterization of the antiglioma activity of a tropism-enhanced adenovirus targeted to the retinoblastoma pathway. J Natl Cancer Inst. 2003;95:652–60.CrossRef

18.

Suzuki K, Fueyo J, Krasnykh V, Reynolds PN, Curiel DT. Alemany R. a conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency. Clin Cancer Res. 2001;7:120–6.PubMed

19.

Greaves M, Maley CC. Clonal evolution in cancer. Nature. 2012;481:306–13.CrossRef

20.

Simon R, Roychowdhury S. Implementing personalized cancer genomics in clinical trials. Nat Rev Discov. 2013;12:358–69.CrossRef

21.

Wistuba II, Gelovani JG, Jacoby JJ, Davis SE, Herbst RS. Methodological and practical challenges for personalized cancer therapies. Nat Rev Oncol. 2011;8:135–41.CrossRef

22.

Klein MJ, Siegal GP. Osteosarcoma: anatomic and histologic variants. Am J Clin Pathol. 2006;125:555–81.CrossRef

23.

Humbert O, Cochet A, Riedinger J-M, Berriolo-Riedinger A, Arnould L, Coudert B, et al. HER2-positive breast cancer: 18F-FDG PET for early prediction of response to trastuzumab plus taxane-based neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging. 2014;41:1525–33. https://doi.org/10.1007/s00259-014-2739-1.CrossRefPubMed

24.

Choi JW, Lee JS, Kim SW, Yun CO. Evolution of oncolytic adenovirus for cancer treatment. Adv Drug Deliv Rev. 2012;64:720–9.CrossRef

25.

Rodriguez-Garcia A, Gimenez-Alejandre M, Rojas JJ, Moreno R, Bazan-Peregrino M, Cascallo M, et al. Safety and efficacy of VCN-01, an oncolytic adenovirus combining fiber HSG-binding domain replacement with RGD and hyaluronidase expression. Clin Cancer Res. 2015;21:1406–18.CrossRef

26.

Lim R, Eaton A, Lee NY, Setton J, Ohri N, Rao S, et al. 18F-FDG PET/CT metabolic tumor volume and total lesion glycolysis predict outcome in oropharyngeal squamous cell carcinoma. J Nucl Med. 2012;53:1506–13.CrossRef

27.

Liao S, Penney BC, Wroblewski K, Zhang H, Simon CA, Kampalath R, et al. Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer. Eur J Nucl Med Mol Imaging. 2012;39:27–38. https://doi.org/10.1007/s00259-011-1934-6.CrossRefPubMed

Title: Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [18F]FDG and sodium [18F]fluoride PET
Authors: María Collantes
Naiara Martínez-Vélez
Marta Zalacain
Lucia Marrodán
Margarita Ecay
María José García-Velloso
Marta María Alonso
Ana Patiño-García
Iván Peñuelas
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-018-5122-y

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2018

Efficacy and safety of concurrent anti-Cancer and anti-tuberculosis chemotherapy in Cancer patients with active Mycobacterium tuberculosis: a retrospective study

Daphnane diterpenes inhibit the metastatic potential of B16F10 murine melanoma cells in vitro and in vivo

Clinical response and pharmacokinetics of bendamustine as a component of salvage R-B(O)AD therapy for the treatment of primary central nervous system lymphoma (PCNSL)

Re-challenging immune checkpoint inhibitor in a patient with advanced non-small cell lung cancer: a case report

Upregulation of FOXM1 leads to diminished drug sensitivity in myeloma

Discontinuation of tyrosine kinase inhibitors in CML patients in real-world clinical practice at a single institution

Keynote webinar | Spotlight on antibody–drug conjugates in cancer