Molecular imaging offers insight into therapy outcomes for neuroendocrine tumor patients

May 14, 2020

A new proof-of-concept study published in the May issue of The Journal of Nuclear Medicine has demonstrated that molecular imaging can be used for identifying early response to 177Lu-DOTATATE treatment in neuroendocrine tumor patients.

Utilizing single photon emission computed tomography (SPECT) imaging with 111In-antiγH2AX-TAT, researchers were able to visualize a DNA damage response marker just days after 177Lu-DOTATATE treatment. Monitoring the DNA damage response in the early days after the radionuclide injection could allow physicians to determine the therapeutic outcome and adapt the therapy regimen accordingly.

The radiobiologic aspects of 177Lu-DOTATATE, as well as other molecular radiotherapies, are underexplored. Radionuclide therapy is largely delivered to neuroendocrine tumor patients on a fixed dose protocol, regardless of body weight or tumor uptake. To justify any increase or decrease in the prescribed radionuclide dose a sustainable metric is needed; however, no metric currently exists.

"One strategy to develop this metric is to determine if sufficient damage has been afflicted to the tumor, which would allow treating physicians to tailor subsequent doses to ensure therapeutic success," said Bart Cornelissen, PhD, associate professor in the department of oncology at the MRC Oxford Institute for Radiation Oncology at the University of Oxford in Oxford, United Kingdom. "In our study, we sought to image the molecular biological effects of 177Lu-DOTATATE radionuclide therapy by visualizing the DNA double-strand break damage response marker γH2AX."

In the study, researchers first exposed six cell lines to external beam therapy or 177Lu-DOTATATE and measured the number of γH2AX foci and the clonogenic survival (which indicate the extent of DNA double-strand break damage). Mice bearing the same cell line were then treated with 177Lu-DOTATATE or sham-treated, and static SPECT images were acquired at one, 24, 48 and 72 hours after administration. Immediately after the first SPECT imaging session, the mice were administered 111In-anti-γH2AX-TAT or 111In-IgG-TAT.

In vitro cell lines exposed to 177Lu-DOTATATE were found to have increased γH2AX foci and decreased clonogenic survival, and reacted very differently than to an equitoxic dose of external beam irradiation. The γH2AX foci induced by 177Lu-DOTATATE in the preclinical models were successfully imaged by SPECT in vivo using 111In-anti-γH2AX-TAT. An accumulation of γH2AX signal was observed over the days after administration of 177Lu-DOTATATE, indicating an increase in DNA damage. Furthermore, γH2AX expression revealed intratumoral and interlesion heterogeneity with the absorbed 177Lu dose, suggesting that different parts of the tumor may react differentially to treatment with 177Lu-DOTATATE.

"The application of this imaging technique could provide a very early indicator of tumor damage without having to wait for changes in tumor volume, which currently may take months to find out," noted Edward O'Neill, postdoctoral researcher in the department of oncology at MRC Oxford Institute for Radiation Oncology at the University of Oxford in Oxford, United Kingdom. "When using therapeutic response assessment with molecular imaging, making rapid decisions becomes possible, including dose reduction to avoid side effects, assessment of combination therapies, or, in the absence of any measurable response, initiation of palliative options designed toward improving quality of life."
This study was made available online in November 2019 ahead of final publication in print in May 2020.

The authors of "Imaging DNA Damage Repair In Vivo After 177Lu-DOTATATE Therapy" include Edward O'Neill, Veerle Kersemans, P. Danny Allen, Julia Baguña Torres, Michael Mosely, Sean Smart, Boon Quan Lee, Nadia Falzone, Katherine A. Vallis and Bart Cornelissen, CRUK/MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford, United Kingdom; Samantha Y.A. Terry, Department of Imaging Chemistry and Biology, King's College London, London, United Kingdom; Mark W. Konijnenberg and Marion de Jong, Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands; and Julie Nonnekens, Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands, Department of Molecular Genetics, Erasmus MC, Rotterdam, The Netherlands, and Oncode Institute, Erasmus MC, Rotterdam, The Netherlands.

Please visit the SNMMI Media Center for more information about molecular imaging and precision imaging. To schedule an interview with the researchers, please contact Rebecca Maxey at (703) 652-6772 or Current and past issues of The Journal of Nuclear Medicine can be found online at

About the Society of Nuclear Medicine and Molecular Imaging

The Journal of Nuclear Medicine (JNM) is the world's leading nuclear medicine, molecular imaging and theranostics journal, accessed close to 10 million times each year by practitioners around the globe, providing them with the information they need to advance this rapidly expanding field.

JNM is published by the Society of Nuclear Medicine and Molecular Imaging (SNMMI), an international scientific and medical organization dedicated to advancing nuclear medicine and molecular imaging--precision medicine that allows diagnosis and treatment to be tailored to individual patients in order to achieve the best possible outcomes. For more information, visit

Society of Nuclear Medicine and Molecular Imaging

Related DNA Damage Articles from Brightsurf:

DNA damage caused by migrating light energy
Ultraviolet light endangers the integrity of human genetic information and may cause skin cancer.

DNA damage triggers reprogramming into stem cells
A joint research team from the National Institute for Basic Biology (NIBB) in Japan, Huazhong Agricultural University in China, and the Czech Academy of Sciences in the Czech Republic has discovered that DNA damage causes cell? to reprogram themselves into stem cells and regenerate new plant bodies in the moss Physcomitrella patens.

Researchers discover how enzyme protects cells from DNA damage
A research team from Mount Sinai has unraveled for the first time the three-dimensional structure and mechanism of a complex enzyme that protects cells from constant DNA damage, opening the door to discovery of new therapeutics for the treatment of chemotherapy-resistant cancers.

This enigmatic protein sculpts DNA to repair harmful damage
Sometimes, when something is broken, the first step to fixing it is to break it even more.

Persistent DNA damage in the placenta affects pregnancy outcomes
Scientists at the Stowers Institute for Medical Research have shown that a dysfunctional placenta can play a previously unrecognized role during the earliest stages of development in mouse models of Cornelia de Lange syndrome.

First systematic report on the tug-of-war between DNA damage and repair
IBS scientists have screened almost 163,000 DNA mutations in 2,700 C. elegans roundworms to shed light on DNA damage.

Study finds that aging neurons accumulate DNA damage
MIT neuroscientists have discovered that an enzyme called HDAC1 is critical for repairing age-related DNA damage to genes involved in memory and other cognitive functions.

DNA damage and faulty repair jointly cause mutations
By analysing genomic data from worms, scientists detailed how mutations are caused by a combination of DNA damage and inaccurate repair.

Scientists recreate DNA damage caused by toxins from smoking
Researchers from the University of York have recreated how toxins from smoking cause unique patterns of DNA damage.

Scientists discover new repair mechanism for alcohol-induced DNA damage
Researchers of the Hubrecht Institute (KNAW) in Utrecht, The Netherlands, and the MRC Laboratory of Molecular Biology in Cambridge, United Kingdom, have discovered a new way in which the human body repairs DNA damage caused by a degradation product of alcohol.

Read More: DNA Damage News and DNA Damage Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to