Collagen-binding ⁶⁸Ga-CBP8 PET/MR in Deep Pelvic Endometriosis: First-in-human Application

Purpose To evaluate the feasibility of collagen-binding ⁶⁸Ga-CBP8 PET/MR for the noninvasive detection of deep infiltrating endometriosis.

A single-case exploratory application of ⁶⁸Ga-CBP8 PET/MR was conducted in a patient with endometriosis as a preliminary step toward a larger IRB-approved prospective study. Imaging was performed 60 min after intravenous administration of ⁶⁸Ga-CBP8. Fused PET/MR images were qualitatively assessed for focal tracer uptake exceeding background. Surgical pathology, assessed in a blinded fashion, served as the reference standard.

A 32-year-old woman with history of endometriosis completed the examination without adverse events. PET/MR demonstrated focal ⁶⁸Ga-CBP8 uptake corresponding on MR to a T2-hypointense plaque located between the left adnexa and the sigmoid colon, suspicious for deep pelvic endometriosis with bowel involvement. Surgical pathology confirmed endometriosis infiltrating the colonic muscularis mucosae and pericolonic tissue with dense fibrosis.

⁶⁸Ga-CBP8 PET/MR is a feasible and promising technique to noninvasively detect deep infiltrating endometriosis, warranting validation in larger prospective studies. Trial Registration ClinicalTrials.gov, NCT06377553. Date of first enrollment: February 5, 2025. Registered April 22, 2024. Similar content being viewed by others Data Availability Data supporting the findings of this study are available from the corresponding author upon reasonable request.

Garcia Garcia JM, Vannuzzi V, Donati C, Bernacchioni C, Bruni P, Petraglia F (2023) Endometriosis: cellular and molecular mechanisms leading to fibrosis. Reprod Sci 30(5):1453–1461. https://doi.org/10.1007/s43032-022-01083-x Rousset P, Florin M, Bharwani N, Touboul C, Monroc M, Golfier F et al (2023) Deep pelvic infiltrating endometriosis: MRI consensus lexicon and compartment-based approach from the ENDOVALIRM group. Diagn Interv Imaging 104(3):95–112. https://doi.org/10.1016/j.diii.2022.09.004 Ueno Y, Kaseki H, Shiraishi T, Nagawa F, Ono A, Fukagawa T et al (2021) Preoperative classification of endometriosis: a narrative review of revised American Society for Reproductive Medicine (r-ASRM), #Enzian, American Association of Gynecologic Laparoscopists (AAGL) 2021, and Numerical Multi-Scoring System of Endometriosis (NMS-E) systems. Gynecol Pelvic Med 8:14–14. https://doi.org/10.21037/gpm-25-3 Yin L, Xu Q, Alhaskawi A, Yang Y, Shi J, Zhou X et al (2025) Assessment of Al18F-NOTA-FAPI-04 PET/CT imaging for visualization and localization of ovarian and peritoneal endometriotic lesions in a rat model. J Radiat Res Appl Sci 18(3):101679. https://doi.org/10.1016/j.jrras.2025.101679 Napolitano R, Speltri G, Martini P, Porto F, Marvelli L, Niorettini A et al (2025) Molecular imaging advances in endometriosis: the promise of radiopharmaceuticals. Molecules 31(1):93. https://doi.org/10.3390/molecules31010093 Harth S, Roller FC, Zeppernick F, Meinhold-Heerlein I, Krombach GA (2023) Deep infiltrating endometriosis: diagnostic accuracy of preoperative magnetic resonance imaging with respect to morphological criteria. Diagnostics (Basel) 13(10):1794. https://doi.org/10.3390/diagnostics13101794 Gerges B, Li W, Leonardi M, Mol BW, Condous G (2021) Meta-analysis and systematic review to determine the optimal imaging modality for the detection of uterosacral ligaments/torus uterinus, rectovaginal septum and vaginal deep endometriosis. Hum Reprod Open. https://doi.org/10.1093/hropen/hoab041 Zou Y, Hu H, Tian R, Wang R (2025) Focal 68Ga-FAPI-04 uptake in endometriosis at the rectouterine pouch. Clin Nucl Med 50(12):e722–e723. https://doi.org/10.1097/RLU.0000000000005846 Burgard C, Rosar F, Ezziddin S, Hamoud BH, Solomayer EF, Laschke MW et al (2025) [68Ga]Ga-FAPI-04 PET/CT in a patient with endometriosis: a potential game changer? Eur J Nucl Med Mol Imaging 52(12):4350–4351. https://doi.org/10.1007/s00259-025-07252-9 Sandler I, Artoul F, Zick A, Ben-Shachar I (2025) 68Ga-FAPI-04 PET/CT demonstrates subtype-specific uptake patterns in endometriosis with added diagnostic value beyond MRI. Clin Nucl Med. https://doi.org/10.1097/RLU.0000000000006092 Blandino AA, Caravan P, Ricciardi R, Bordeianou LG, Kunitake H, Goldstone RN et al (2026) Collagen-binding probe PET/MR for distinguishing fibrotic from inflammatory strictures in Crohn’s disease. Eur J Nucl Med Mol Imaging. https://doi.org/10.1007/s00259-025-07741-x Désogère P, Tapias LF, Hariri LP, Rotile NJ, Rietz TA, Probst CK et al (2017) Type I collagen–targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aaf4696 Montesi SB, Izquierdo-Garcia D, Désogère P, Abston E, Liang LL, Digumarthy S et al (2019) Type I collagen–targeted positron emission tomography imaging in idiopathic pulmonary fibrosis: first-in-human studies. Am J Respir Crit Care Med 200(2):258–261. https://doi.org/10.1164/rccm.201903-0503LE Abston E, Zhou IY, Saenger JA, Shuvaev S, Akam E, Esfahani SA et al (2024) Noninvasive quantification of radiation-induced lung injury using a targeted molecular imaging probe. Int J Radiat Oncol Biol Phys 118(5):1228–1239. https://doi.org/10.1016/j.ijrobp.2023.11.032 Montesi SB, Cosgrove GP, Turner SM, Zhou IY, Efthimiou N, Susnjar A et al (2025) Dual αvβ6 and αvβ1 Inhibition over 12 Weeks Reduces Active Type I Collagen Deposition in Individuals with Idiopathic Pulmonary Fibrosis: A Phase 2, Double-Blind, Placebo-controlled Clinical Trial. Am J Respir Crit Care Med 211(7):1229–1240. https://doi.org/10.1164/rccm.202410-1934OC Esfahani SA, Ma H, Krishna S, Shuvaev S, Sabbagh M, Deffler C et al (2024) Collagen type I PET/MRI enables evaluation of treatment response in pancreatic cancer in pre-clinical and first-in-human translational studies. Theranostics 14(15):5745–5761. https://doi.org/10.7150/thno.100116 Xiong S, Whitehurst CE, Li L, Heo GS, Lai CW, Jain U et al (2022) Reverse translation approach generates a signature of penetrating fibrosis in Crohn’s disease that is associated with anti-TNF response. Gut 71(7):1289–1301. https://doi.org/10.1136/gutjnl-2020-323405 Talebloo N, Bernal MAO, Kenyon E, Mallett CL, Fazleabas A, Moore A (2023) Detection of endometriosis lesions using Gd-based collagen I targeting probe in murine models of endometriosis. Mol Imaging Biol 25(5):833–843. https://doi.org/10.1007/s11307-023-01833-6 Imperiale L, Nisolle M, Noël JC, Fastrez M (2023) Three types of endometriosis: pathogenesis, diagnosis and treatment. State of the art. J Clin Med 12(3):994. https://doi.org/10.3390/jcm12030994

Nothing to acknowledge. Funding Peter Caravan: Grant S10OD028499 is acknowledged for supporting radiochemistry infrastructure. Leo L. Tsai received research study support from the Division of Abdominal Radiology at Massachusetts General Hospital. Author information Authors and Affiliations Contributions Antonino Andrea Blandino: Supervision, Data interpretation, Writing – original draft, Writing – review & editing. Peter Caravan: Conceptualization, Data interpretation, Writing – review & editing. Anuradha S. Shenoy-Bhangle: Data interpretation, Writing – review & editing. Elio Quiros: Data interpretation, Writing – review & editing. Mario V. Russo: Data interpretation, Writing – review & editing. Michael J. Misialek: Data interpretation, Writing – review & editing. Liran Domachevsky: Data interpretation, Writing – review & editing. Leo L. Tsai: Data interpretation, Writing – review & editing. Onofrio Antonio Catalano: Conceptualization, Supervision, Data interpretation, Writing – review & editing. All authors contributed to the conception/design of the study or to data interpretation, and to critical revision of the manuscript. All authors read and approved the final version of the manuscript and agreed to be accountable for all aspects of the work. Corresponding author Ethics declarations Ethics Approval and Consent This prospective study was approved by the Institutional Review Board of Massachusetts General Hospital (protocol: 2023P000955) and registered at clinicaltrials.gov (protocol: NCT06377553). The study was conducted in accordance with the Declaration of Helsinki and all patients gave their full written informed consent. Competing Interests The authors Antonino Andrea Blandino, Anuradha S. Shenoy-Bhangle, Elio Quiros, Mario V. Russo, Michael J. Misialek, Liran Domachevsky have no competing—financial or non-financial—interests to declare that are relevant to the content of this article. Peter Caravan has equity in Lumina Pharmaceuticals and Reveal Pharmaceuticals; has consulting income from Lumina Pharmaceuticals and Reveal Pharmaceuticals; received research support from Canon Medical USA, the Crohn’s and Colitis Foundation, and Takeda Pharmaceuticals. Dr. Caravan’s interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies. Onofrio Antonio Catalano received support from Takeda Pharmaceuticals Co. Leo L. Tsai received research study support from the Division of Abdominal Radiology at Massachusetts General Hospital. Additional information Publisherʼs Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Blandino, A.A., Caravan, P., Shenoy-Bhangle, A.S. et al. Collagen-binding ⁶⁸Ga-CBP8 PET/MR in Deep Pelvic Endometriosis: First-in-human Application. Mol Imaging Biol (2026). https://doi.org/10.1007/s11307-026-02125-5 Received: Revised: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s11307-026-02125-5