Researchers from the University of Oxford say an experimental imaging agent they have tested may help to locate endometriosis lesions that standard scans can miss and could represent a non-invasive tool for diagnosing and monitoring the condition, which could benefit millions of women across the world.
Working with the radiopharmaceutical company Serac Healthcare, the team from the Nuffield Department of Women’s & Reproductive Health (NDWRH) have published the findings of their Phase II trial into the effectiveness of the new agent, 99mTc-maraciclatide, in The Lancet Obstetrics and Gynaecology.
Their findings not only highlight the potential of nuclear imaging as a valuable tool in the diagnosis and management of endometriosis, but also suggest this approach could reduce the number of women undergoing unnecessary surgery, while improving the accuracy and speed of diagnosis.
Endometriosis is a common inflammatory disease that affects up to one in 10 women of childbearing age, or 190 million women worldwide. The condition occurs when tissue similar to the lining of the womb is found outside that organ, predominantly in the pelvis, but sometimes elsewhere in the body, such as lungs. It can cause severe pain, heavy bleeding, fatigue and fertility problems. Those with endometriosis typically experience an eight- to 12-year wait for diagnosis, requiring numerous visits to doctors and hospitals, along with multiple scans.
The research, which was supported by the NIHR Biomedical Research Centre: Oxford, highlights that 99mTc-maraciclatide has potential as:
- A novel non-invasive diagnostic test, particularly for superficial peritoneal endometriosis (SPE), which cannot be reliably detected by conventional imaging techniques and currently requires laparoscopic surgery for a definitive diagnosis
- A tool to allow the disease to be monitored, removing uncertainty around whether the disease has returned
- A marker of the response to treatment, which could support the development of new therapies
99mTc-maraciclatide is a radio-labelled tracer that binds to a protein (αvβ3 integrin) linked to angiogenesis – the formation of new blood vessels – which is known to be key factor in the establishment and growth of endometriotic lesions. The DETECT study describes, for the first time, the use of 99mTc-maraciclatide as a potential tool for highlighting and diagnosing endometriosis on a scan.
Key findings:
- The DETECT study demonstrated a high correlation between where maraciclatide was taken up and what clinicians saw on a laparoscopy. This occurred across all types of endometriotic lesions, including hard-to-detect SPE, the earliest stage of endometriosis, which is found in 80 per cent of all cases that are diagnosed through laparoscopy.
- Imaging with 99mTc-maraciclatide picked up endometriosis that conventional imaging methods[LG1] had missed.
- Imaging results were consistent with the surgical findings in 16 out of 19 cases; endometriosis was seen in 14 out of 17 cases where surgery confirmed the disease was present, including two affecting the chest (thoracic endometriosis)
- No false positives were reported in this study
- Imaging with 99mTc-maraciclatide was able to detect lesions across all types of endometriosis, suggesting the scan could be applied to various patient groups
- The tracer was well tolerated and acceptability was high
Dr Tatjana Gibbons, lead author on the paper and investigator on the study from the Nuffield Department of Women’s and Reproductive Health, University of Oxford said: “These exciting findings indicate that maraciclatide offers a highly promising diagnostic and monitoring tool, particularly for superficial peritoneal endometriosis, which is the most common and yet the hardest type of endometriosis to identify.
“We are hugely grateful to the patients who have participated in the DETECT study without whom investigating this diagnostic approach would not have been possible.”
Professor Christian Becker, Co-Director of the Endometriosis CaRe Centre in Oxford, co-lead on the study and joint senior co-author on the paper, added: “Novel, non-invasive diagnostic tests for endometriosis are a global research priority. The diagnostic challenge of endometriosis, which presents with varied and non-specific symptoms, is exacerbated by an absence of clinically validated biomarkers and the limitations of currently available imaging techniques.
“If these Phase II results are reproduced in the Phase III studies, maraciclatide has the potential to be an extremely valuable tool, as it could both reduce diagnostic delays and provide a validated endpoint for the development of new therapeutics.”
David Hail, CEO of Serac Healthcare, commented: “The completion and publication of this clinical study mark a pivotal achievement for Serac Healthcare. These data, from a representative patient population, including women receiving hormone therapy, provide evidence of maraciclatide’s anticipated real-world performance. “With FDA (the US Federal Drugs Agency) Fast Track Designation and agreed Phase III study designs, we are now advancing to validate these findings in larger trials and progress to regulatory submission.”
Professor Krina Zondervan, Co-Director of the Endometriosis CaRe Centre, Head of Department at the NDWRH, Co-theme Lead for the NIHR BRC Oxford’s Surgical Innovation Theme, co-lead on the study and joint senior co-author on the paper, said: “Superficial peritoneal endometriosis, the most prevalent subtype of endometriosis, currently evades reliable detection, leaving women no choice for diagnosis other than invasive surgery.
“If these results are confirmed in larger Phase III studies, imaging with maraciclatide could transform clinical research and practice and potentially empower the development of treatments for women across the globe.”
About the Phase II trial:
This was an exploratory, open-label, single-centre, phase II study evaluating pre-operative imaging in 20 individuals with suspected or confirmed pelvic or thoracic endometriosis using a SPECT-CT imaging test with intravenous 99mTc-maraciclatide.
The primary outcome was how the radiological and surgical findings aligned in those patients who completed both imaging and surgery, with the surgical report on lesion type and location being compared to the scan images.
Ten of the participants with SPE had prior imaging using traditional methods, such as transvaginal ultrasound and/or MRI in the previous 12 months, none of which had detected SPE.
Phase III multi-centre international studies are due to start later this year.
In July 2024, 99mTc-maraciclatide was granted Fast Track Designation by the FDA as a diagnostic agent for use with SPECT CT for the visualisation and diagnosis of SPE. The FDA Fast track is intended to facilitate the development of drugs to treat or diagnose serious conditions and fill an unmet medical need.