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Lymph Node Activation by PET/CT Following Vaccination With Licensed Vaccines for Human Papillomaviruses

Coates, Emily E. PhD; Costner, Pamela J. RN, BSN; Nason, Martha C. PhD; Herrin, Douglas M. MD; Conant, Shielah BS, CNMT; Herscovitch, Peter MD; Sarwar, Uzma N. MD; Holman, Lasonji RN, NP; Mitchell, Jillian BS; Yamshchikov, Galina MS; Koup, Richard A. MD, BS; Graham, Barney S. MD, PhD; Millo, Corina M. MD; Ledgerwood, Julie E. DO the VRC 900 Study Team

doi: 10.1097/RLU.0000000000001603
Original Articles

Background While PET using 18F-FDG is most commonly used for imaging malignant tumors, vaccination is known to cause transient inflammation of lymph nodes inducing positive findings on 18F-FDG PET scans. The pattern, magnitude, and duration of lymph node activation following vaccination have not been clearly defined. Furthermore, the addition of adjuvants to vaccines can further enhance the immune response. The presented study was designed to define lymph node activation following administration of the Food and Drug Administration–licensed human papillomavirus vaccines, Cervarix and Gardasil, which contain similar antigens with different adjuvants.

Methods Twenty-seven women aged 18 to 25 years were randomized to receive either Cervarix or Gardasil in the clinical trial VRC 900. Fifteen subjects participated in the PET/CT portion of the trial and received scans of lymph node activation at prevaccination and “1 week” (8–14 days) and “1 month” (23–36 days) after the first or third vaccination.

Results PET/CT scans revealed that all vaccine recipients had ipsilateral axillary lymph node activity. Three of 4 Cervarix recipients also showed contralateral lymph node activity 1 month after the first vaccination. For both Cervarix and Gardasil, the SUV activity resolved over time, with activity extended up to day 37 after the first and third vaccinations.

Conclusions Following intramuscular vaccination, there were no major differences between duration of uptake and intensity of SUV between Cervarix and Gardasil recipients in ipsilateral axillary lymph nodes. Contralateral node activation was detected up to 1 month after the first vaccination in Cervarix recipients only, possibly reflecting differences in vaccine adjuvant formulation.

From the *Vaccine Research Center, National Institute of Allergy and Infectious Disease, †Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Disease, and ‡Positron Emission Tomography Department, Clinical Center, National Institutes of Health, Bethesda, MD.

Received for publication April 11, 2016; revision accepted January 14, 2017.

The VRC 902 Study Team includes Mary E. Enama, Ingelise Gordon, Sarah Plummer, Cynthia Starr Hendel, Laura Novik, Kathy Zephir, Floreliz Mendoza, Jamie Saunders, Nina Berkowitz, Brandon Wilson, Tanya Clarke, Sandra Sitar, Brenda Larkin, Joseph Casazza, Sheryl Young, Leejah Chang, Olga Vasilenko, Iris Pittman, Hope Decederfelt, LaChonne Stanford, and Robert T. Bailer.

Conflicts of interest and sources of funding: This study was funded by the National Institutes of Health, National Institutes Intramural Research Program. #NCT01132859. None declared to all authors.

The findings and conclusions in this report are those of the authors and do not necessarily reflect the views of the funding agency or collaborators.

Correspondence to: Julie E. Ledgerwood, DO, National Institute of Allergy and Infectious Diseases, 10 Center Drive MSC 1912, Bethesda, MD 20892. E-mail:

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.