Head and neck tumors angiogenesis imaging with 68Ga-NODAGA-RGD in comparison to 18F-FDG PET/CT: a pilot study

Steve Durante, Vincent Dunet, François Gorostidi, Periklis Mitsakis, Niklaus Schaefer, Judith Delage, John O Prior, Steve Durante, Vincent Dunet, François Gorostidi, Periklis Mitsakis, Niklaus Schaefer, Judith Delage, John O Prior

Abstract

Background: Angiogenesis plays an important role in head and neck squamous cell carcinoma (HNSCC) progression. This pilot study was designed to compare the distribution of 68Ga-NODAGA-RGD PET/CT for imaging αvβ3 integrins involved in tumor angiogenesis to 18F-FDG PET/CT in patients with HNSCC.

Material and methods: Ten patients (aged 58.4 ± 8.3 years [range, 44-73 years], 6 males, 4 females) with a total of 11 HNSCC were prospectively enrolled. Activity mapping and standard uptake values (SUV) from both 68Ga-NODAGA-RGD and 18F-FDG PET/CT scans were recorded for primary tumor and compared with the Wilcoxon signed-rank test. The relation between the SUV of both tracers was assessed using the Spearman correlation.

Results: All HNSCC tumors were visible with both tracers. Quantitative analysis showed higher 18F-FDG SUVmax in comparison to 68Ga-NODAGA-RGD (14.0 ± 6.1 versus 3.9 ± 1.1 g/mL, p = 0.0017) and SUVmean (8.2 ± 3.1 versus 2.0 ± 0.8 g/mL, p = 0.0017). Both 18F-FDG and 68Ga-NODAGA-RGD uptakes were neither correlated with grade, HPV status nor p16 protein expression (p ≥ 0.17).

Conclusion: All HNSCC tumors were detected with both tracers with higher uptake with 18F-FDG, however. 68Ga-NODAGA-RGD has a different spatial distribution than 18F-FDG bringing different tumor information.

Trial registration: NCT, NCT02666547. Registered 12.8.2012.

Keywords: 18F-FDG; 68Ga-NODAGA-RGD; Angiogenesis; Head and neck cancer; PET.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Example of axial and coronal 18F-FDG and 68Ga-NODAGA-RGD PET/CT 3-D volume of interest semi-automatically delineated on a 42%  SUVmax threshold for patient #8 using a parallelepipedal bounding box
Fig. 2
Fig. 2
Maximum intensity projection (MIP) of 18F-FDG and 68Ga-NODAGA-RGD PET/CT in four patients. HNSCC primary tumor had a significant uptake in all patients. Lymph nodes also demonstrated a significant uptake as seen in patients #1 and #6. A focal uptake is detectable with 68Ga-NODAGA-RGD PET/CT in the liver of patient #2, corresponding to the gallbladder. Inflammatory capsulitis of the glenohumeral joint was also observed in patients #1 and #6
Fig. 3
Fig. 3
Box plot comparison of 18F-FDG and 68Ga-NODAGA-RGD SUVmax in organs. SUVmax was significantly different between both tracers in all organs (all p < 0.037), except in the thyroid, the gut (small intestine and colon), and the bladder (not shown) (all p > 0.10). The most significant difference was observed for the brain and the myocardium, which presented only minimal 68Ga-NODAGA-RGD uptake compared to 18F-FDG
Fig. 4
Fig. 4
Comparative MRI, 18F-FDG, and 68Ga-NODAGA-RGD PET/CT of patient #8. Axial PET/CT fusion slices of a 69-year-old man with a moderate differentiated base tong SCC. The images show different tumor-to-background ratios in between the two radiotracers 18F-FDG PET/CT (a, b) vs. 68Ga-NODAGA-RGD PET/CT (c, d), and also a slightly different distribution of activity within the tumor bed when compared with the MR images e T2w and f ADC map of diffusion
Fig. 5
Fig. 5
Comparative 18F-FDG (a, b), 68Ga-NODAGA-RGD PET/CT (c, d), and MRI (e T2w axial, f T1w post Gadolinium, g ADC map of diffusion), of patient #9 (59-year man with moderate differentiated left tonsil squamous cell carcinoma). The 18F-FDG and 68Ga-NODAGA-RGD PET images showed different signal-to-noise ratios and a slightly different distribution of activity within the tumor bed. The left cervical lymph node showed a photopenic center with absence of tracer uptake for both tracers corresponding to necrosis on MRI
Fig. 6
Fig. 6
Correlation between a18F-FDG and 68Ga-NODAGA-RGD SUVmax, which was systematically lower (slope of the reduced major axis 0.22 < 1.00) and b68Ga-NODAGA-RGD tracer avid tumor volume (TATV), which was systematically higher than 18F-FDG metabolic tumor volume (MTV) (slope of the reduced major axis 2.91 > 1.00)

References

    1. Mirghani H, Bellera C, Delaye J, Dolivet G, Fakhry N, Bozec A, et al. Prevalence and characteristics of HPV-driven oropharyngeal cancer in France. Cancer Epidemiol. 2019;61:89–94. doi: 10.1016/j.canep.2019.05.007.
    1. Broglie MA, Stoeckli SJ, Sauter R, Pasche P, Reinhard A, de Leval L, et al. Impact of human papillomavirus on outcome in patients with oropharyngeal cancer treated with primary surgery. Head Neck. 2017;39:2004–2015. doi: 10.1002/hed.24865.
    1. Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29:4294–4301. doi: 10.1200/JCO.2011.36.4596.
    1. Escott EJ. Role of positron emission tomography/computed tomography (PET/CT) in head and neck cancer. Radiol Clin North Am. 2013;51:881–893. doi: 10.1016/j.rcl.2013.05.002.
    1. Helsen N, Van den Wyngaert T, Carp L, De Bree R, VanderVeken OM, De Geeter F, et al. Quantification of 18F-fluorodeoxyglucose uptake to detect residual nodal disease in locally advanced head and neck squamous cell carcinoma after chemoradiotherapy: results from the ECLYPS study. Eur J Nucl Med Mol Imaging. 2020. 10.1007/s00259-020-04710-4.
    1. Rohde M, Dyrvig AK, Johansen J, Sorensen JA, Gerke O, Nielsen AL, et al. 18F-fluoro-deoxy-glucose-positron emission tomography/computed tomography in diagnosis of head and neck squamous cell carcinoma: a systematic review and meta-analysis. Eur J Cancer. 2014;50:2271–2279. doi: 10.1016/j.ejca.2014.05.015.
    1. Van den Wyngaert T, Helsen N, Carp L, Hakim S, Martens MJ, Hutsebaut I, et al. Fluorodeoxyglucose-positron emission tomography/computed tomography after concurrent chemoradiotherapy in locally advanced head-and-neck squamous cell cancer: the ECLYPS study. J Clin Oncol. 2017;35:3458–3464. doi: 10.1200/JCO.2017.73.5845.
    1. Beer AJ, Grosu AL, Carlsen J, Kolk A, Sarbia M, Stangier I, et al. [18F]galacto-RGD positron emission tomography for imaging of alphavbeta3 expression on the neovasculature in patients with squamous cell carcinoma of the head and neck. Clin Cancer Res. 2007;13:6610–6616. doi: 10.1158/1078-0432.CCR-07-0528.
    1. Beer AJ, Haubner R, Goebel M, Luderschmidt S, Spilker ME, Wester HJ, et al. Biodistribution and pharmacokinetics of the alphavbeta3-selective tracer 18F-galacto-RGD in cancer patients. J Nucl Med. 2005;46:1333–1341.
    1. Beer AJ, Haubner R, Sarbia M, Goebel M, Luderschmidt S, Grosu AL, et al. Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res. 2006;12:3942–3949. doi: 10.1158/1078-0432.CCR-06-0266.
    1. Schnell O, Krebs B, Carlsen J, Miederer I, Goetz C, Goldbrunner RH, et al. Imaging of integrin alpha(v)beta(3) expression in patients with malignant glioma by [18F] Galacto-RGD positron emission tomography. Neuro Oncol. 2009;11:861–870. doi: 10.1215/15228517-2009-024.
    1. Beer AJ, Niemeyer M, Carlsen J, Sarbia M, Nahrig J, Watzlowik P, et al. Patterns of alphavbeta3 expression in primary and metastatic human breast cancer as shown by 18F-Galacto-RGD PET. J Nucl Med. 2008;49:255–259. doi: 10.2967/jnumed.107.045526.
    1. Al-Abd AM, Alamoudi AJ, Abdel-Naim AB, Neamatallah TA, Ashour OM. Anti-angiogenic agents for the treatment of solid tumors: potential pathways, therapy and current strategies - a review. J Adv Res. 2017;8:591–605. doi: 10.1016/j.jare.2017.06.006.
    1. Kong DH, Kim MR, Jang JH, Na HJ, Lee S. A review of anti-angiogenic targets for monoclonal antibody cancer therapy. Int J Mol Sci. 2017;18. 10.3390/ijms18081786.
    1. Zhernosekov KP, Filosofov DV, Baum RP, Aschoff P, Bihl H, Razbash AA, et al. Processing of generator-produced 68Ga for medical application. J Nucl Med. 2007;48:1741–1748. doi: 10.2967/jnumed.107.040378.
    1. Gnesin S, Mitsakis P, Cicone F, Deshayes E, Dunet V, Gallino AF, et al. First in-human radiation dosimetry of (68)Ga-NODAGA-RGDyK. EJNMMI Res. 2017;7:43. doi: 10.1186/s13550-017-0288-x.
    1. Gaertner FC, Kessler H, Wester HJ, Schwaiger M, Beer AJ. Radiolabelled RGD peptides for imaging and therapy. Eur J Nucl Med Mol Imaging. 2012;39(Suppl 1):S126–S138. doi: 10.1007/s00259-011-2028-1.
    1. Zhai C, Franssen GM, Petrik M, Laverman P, Summer D, Rangger C, et al. Comparison of Ga-68-labeled fusarinine C-based multivalent RGD conjugates and [(68)Ga]NODAGA-RGD-in vivo imaging studies in human xenograft tumors. Mol Imaging Biol. 2016;18:758–767. doi: 10.1007/s11307-016-0931-3.
    1. Van Der Gucht A, Pomoni A, Jreige M, Allemann P, Prior JO. 68Ga-NODAGA-RGDyK PET/CT imaging in esophageal cancer: first-in-human imaging. Clin Nucl Med. 2016;41:e491–e4e2. doi: 10.1097/RLU.0000000000001365.
    1. Haubner R, Finkenstedt A, Stegmayr A, Rangger C, Decristoforo C, Zoller H, et al. [(68)Ga]NODAGA-RGD - metabolic stability, biodistribution, and dosimetry data from patients with hepatocellular carcinoma and liver cirrhosis. Eur J Nucl Med Mol Imaging. 2016;43:2005–2013. doi: 10.1007/s00259-016-3396-3.
    1. Isal S, Pierson J, Imbert L, Clement A, Collet C, Pinel S, et al. PET imaging of (68)Ga-NODAGA-RGD, as compared with (18)F-fluorodeoxyglucose, in experimental rodent models of engrafted glioblastoma. EJNMMI Res. 2018;8:51. doi: 10.1186/s13550-018-0405-5.
    1. Pohle K, Notni J, Bussemer J, Kessler H, Schwaiger M, Beer AJ. 68Ga-NODAGA-RGD is a suitable substitute for (18)F-Galacto-RGD and can be produced with high specific activity in a cGMP/GRP compliant automated process. Nucl Med Biol. 2012;39:777–784. doi: 10.1016/j.nucmedbio.2012.02.006.
    1. Liu JF, Deng WW, Chen L, Li YC, Wu L, Ma SR, et al. Inhibition of JAK2/STAT3 reduces tumor-induced angiogenesis and myeloid-derived suppressor cells in head and neck cancer. Mol Carcinog. 2018;57:429–439. doi: 10.1002/mc.22767.
    1. Knetsch PA, Petrik M, Griessinger CM, Rangger C, Fani M, Kesenheimer C, et al. [68Ga]NODAGA-RGD for imaging alphavbeta3 integrin expression. Eur J Nucl Med Mol Imaging. 2011;38:1303–1312. doi: 10.1007/s00259-011-1778-0.
    1. Terry SY, Abiraj K, Frielink C, van Dijk LK, Bussink J, Oyen WJ, et al. Imaging integrin alphavbeta3 on blood vessels with 111In-RGD2 in head and neck tumor xenografts. J Nucl Med. 2014;55:281–286. doi: 10.2967/jnumed.113.129668.
    1. Okami K. Clinical features and treatment strategy for HPV-related oropharyngeal cancer. Int J Clin Oncol. 2016;21:827–835. doi: 10.1007/s10147-016-1009-6.
    1. Terry SY, Abiraj K, Lok J, Gerrits D, Franssen GM, Oyen WJ, et al. Can 111In-RGD2 monitor response to therapy in head and neck tumor xenografts? J Nucl Med. 2014;55:1849–1855. doi: 10.2967/jnumed.114.144394.
    1. Chen SH, Wang HM, Lin CY, Chang JT, Hsieh CH, Liao CT, et al. RGD-K5 PET/CT in patients with advanced head and neck cancer treated with concurrent chemoradiotherapy: results from a pilot study. Eur J Nucl Med Mol Imaging. 2016;43:1621–1629. doi: 10.1007/s00259-016-3345-1.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren