RANO criteria for response assessment of brain metastases based on amino acid PET imaging

Nathalie L Albert¹, Norbert Galldiks^{2

3

4}, Benjamin M Ellingson⁵, Martin J van den Bent⁶, Susan M Chang⁷, Francesco Cicone⁸, Eng-Siew Koh^{9

10}, Ian Law¹¹, Emilie Le Rhun¹², Maximilian J Mair^{1

13}, Jan-Michael Werner^{2

3

4

13}, Anna S Berghoff¹³, Julia Furtner¹⁴, Giuseppe Minniti^{15

16}, Andrew M Scott^{17

18}, Susan C Short¹⁹, Jana Ivanidze²⁰, Derek R Johnson²¹, Bogdana Suchorska²², Nelleke Tolboom²³, Joerg-Christian Tonn²⁴, Antoine Verger²⁵, Evanthia Galanis²⁶, Priscilla K Brastianos²⁷, Patrick Y Wen²⁸, Michael Weller²⁹, Nancy U Lin³⁰, Matthias Preusser³¹

Affiliations

¹ Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany.
² Department of Neurology, Faculty of Medicine, University Hospital Cologne, Cologne, Germany.
³ Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany.
⁴ Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, Cologne, Germany.
⁵ UCLA Brain Tumor Imaging Laboratory, Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁶ The Brain Tumour Center at the Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
⁷ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
⁸ Nuclear Medicine Unit, Department of Experimental and Clinical Medicine, 'Magna Græcia' University of Catanzaro, Catanzaro, Italy.
⁹ Department of Radiation Oncology, Liverpool and Macarthur Cancer Therapy Centre, Liverpool, New South Wales, Australia.
¹⁰ South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
¹¹ Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark.
¹² Department of Medical Oncology and Hematology, University Hospital and University of Zurich, Zurich, Switzerland.
¹³ Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
¹⁴ Research Center for Medical Image Analysis and Artificial Intelligence, Faculty of Medicine and Dentistry, Danube Private University, Krems, Austria.
¹⁵ Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Policlinico Umberto I, Rome, Italy.
¹⁶ IRCCS Neuromed, Pozzilli, Italy.
¹⁷ Department of Molecular Imaging and Therapy, Austin Health and University of Melbourne, Melbourne, Victoria, Australia.
¹⁸ Olivia Newton-John Cancer Research Institute and School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia.
¹⁹ Leeds Institute of Medical Research at St James's, the University of Leeds, Leeds, UK.
²⁰ Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
²¹ Division of Nuclear Medicine, Department of Radiology, Mayo Clinic, Rochester, MN, USA.
²² Department of Neurosurgery, Heidelberg University Hospital, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany.
²³ Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
²⁴ Department of Neurosurgery, LMU University Hospital, LMU Munich, Munich, Germany.
²⁵ Department of Nuclear Medicine and Nancyclotep Imaging Platform, CHRU Nancy and IADI INSERM UMR 1254, Université de Lorraine, Nancy, France.
²⁶ Department of Oncology, Mayo Clinic, Rochester, MN, USA.
²⁷ Krantz Center for Cancer Research, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
²⁸ Center for Neuro-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
²⁹ Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
³⁰ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
³¹ Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria. matthias.preusser@meduniwien.ac.at.

PMID: 40341837
DOI: 10.1038/s41591-025-03633-7

Review

RANO criteria for response assessment of brain metastases based on amino acid PET imaging

Nathalie L Albert et al. Nat Med. 2025 May.

. 2025 May;31(5):1424-1430.

doi: 10.1038/s41591-025-03633-7. Epub 2025 May 8.

Authors

Affiliations

¹ Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Munich, Germany.
² Department of Neurology, Faculty of Medicine, University Hospital Cologne, Cologne, Germany.
³ Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany.
⁴ Center of Integrated Oncology Aachen Bonn Cologne Düsseldorf, Cologne, Germany.
⁵ UCLA Brain Tumor Imaging Laboratory, Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁶ The Brain Tumour Center at the Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
⁷ Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
⁸ Nuclear Medicine Unit, Department of Experimental and Clinical Medicine, 'Magna Græcia' University of Catanzaro, Catanzaro, Italy.
⁹ Department of Radiation Oncology, Liverpool and Macarthur Cancer Therapy Centre, Liverpool, New South Wales, Australia.
¹⁰ South Western Sydney Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
¹¹ Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark.
¹² Department of Medical Oncology and Hematology, University Hospital and University of Zurich, Zurich, Switzerland.
¹³ Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
¹⁴ Research Center for Medical Image Analysis and Artificial Intelligence, Faculty of Medicine and Dentistry, Danube Private University, Krems, Austria.
¹⁵ Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Policlinico Umberto I, Rome, Italy.
¹⁶ IRCCS Neuromed, Pozzilli, Italy.
¹⁷ Department of Molecular Imaging and Therapy, Austin Health and University of Melbourne, Melbourne, Victoria, Australia.
¹⁸ Olivia Newton-John Cancer Research Institute and School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia.
¹⁹ Leeds Institute of Medical Research at St James's, the University of Leeds, Leeds, UK.
²⁰ Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
²¹ Division of Nuclear Medicine, Department of Radiology, Mayo Clinic, Rochester, MN, USA.
²² Department of Neurosurgery, Heidelberg University Hospital, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany.
²³ Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
²⁴ Department of Neurosurgery, LMU University Hospital, LMU Munich, Munich, Germany.
²⁵ Department of Nuclear Medicine and Nancyclotep Imaging Platform, CHRU Nancy and IADI INSERM UMR 1254, Université de Lorraine, Nancy, France.
²⁶ Department of Oncology, Mayo Clinic, Rochester, MN, USA.
²⁷ Krantz Center for Cancer Research, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
²⁸ Center for Neuro-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
²⁹ Department of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
³⁰ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
³¹ Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria. matthias.preusser@meduniwien.ac.at.

PMID: 40341837
DOI: 10.1038/s41591-025-03633-7

Erratum in

Author Correction: RANO criteria for response assessment of brain metastases based on amino acid PET imaging.
Albert NL, Galldiks N, Ellingson BM, van den Bent MJ, Chang SM, Cicone F, Koh ES, Law I, Le Rhun E, Mair MJ, Werner JM, Berghoff AS, Furtner J, Minniti G, Scott AM, Short SC, Ivanidze J, Johnson DR, Suchorska B, Tolboom N, Tonn JC, Verger A, Galanis E, Brastianos PK, Wen PY, Weller M, Lin NU, Preusser M. Albert NL, et al. Nat Med. 2025 Aug;31(8):2816. doi: 10.1038/s41591-025-03819-z. Nat Med. 2025. PMID: 40490563 No abstract available.

Abstract

Novel diagnostic and therapeutic opportunities are needed to improve medical care and outcome of patients with brain metastases, a frequent and severe complication of several cancer types. Currently, magnetic resonance imaging (MRI) is the primary method used for detection, treatment planning and disease monitoring in patients with brain metastases, but this method has limitations. These limitations mean that MRI can inform on lesion size but cannot directly measure the activity or viability of tumor tissue. Positron emission tomography (PET) imaging, however, can visualize metabolically active tumor cells and is therefore increasingly incorporated into cancer care to assess tumor burden and response to treatment. Here, we define the PET Response Assessment in Neuro-Oncology (RANO) for brain metastasis (BM) 1.0 criteria for metabolic response assessment of brain metastases using amino acid PET. By introducing an innovative endpoint for next-generation clinical trials, the PET RANO BM 1.0 criteria aim to facilitate development of novel therapies for patients with brain metastases.

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Conflict of interest statement

Competing interests: N.L.A. has received honoraria for lectures, consultation or advisory board participation from Novartis, Advanced Accelerator Applications, ABX, Telix Pharmaceuticals, OncLive, MEDSIR and Servier and research funding from Novocure and Telix Pharmaceuticals. N.G. received honoraria for lectures from Blue Earth Diagnostics, for advisory board participation from Telix Pharmaceuticals and Servier and for consultancy services from Telix Pharmaceuticals. B.M.E. reports research funding from Siemens, honoraria for consultancy and/or advisory or data monitoring board participation from Alpheus Medical, Carthera, Chimerix, Ellipses Pharma, Erasca, the Global Coalition for Adaptive Research, Imaging Endpoints, Medicenna, Voiant, Medscape, Monteris, Neosoma, Nerviano Medical Sciences, Orbus Therapeutics, Sagimet Biosciences, Sapience Therapeutics, Servier Pharmaceuticals, SonALAsense, Sunitomo Dainippon Pharma Oncology, Telix, Third Rock Ventures and the NIH/NCI Cancer Imaging Steering Committee. M.J.v.d.B. has received research support from Boehringer Ingelheim, honoraria for consultancy to or participation in advisory boards from Servier, AnHeart Therapeutics, Boehringer Ingelheim, Fore Biotherapeutics, Genenta, Incyte, Chimerix, Alexion and SymBio Pharma and support for travel from Servier. S.M.C. has no COI to disclose. F.C. has no COI to disclose. E.-S.K. has received honoraria for advisory board participation from Telix and Servier. I.L. has received honoraria for lectures and consultation from Telix Pharmaceuticals and Ribocure. E.L.R. has received research grants from Bristol Myers Squibb and honoraria for lectures or advisory board participation or consulting from Bayer, Biodexa/Sitoxi, Janssen, LEO Pharma, Pierre Fabre, Roche, Seattle Genetics and Servier. M.J.M. has received research funding from Bristol Myers Squibb and travel support from Pierre Fabre. J.-M.W. has no COI to disclose. A.S.B. has research support from Daiichi Sankyo and Roche and honoraria for lectures, consultation or advisory board participation from Roche, Bristol Myers Squibb, Merck, Daiichi Sankyo, AstraZeneca, CeCaVa, Seagen, Alexion and Servier as well as travel support from Roche, Amgen and AbbVie. J.F. has received honoraria for lectures, consultation or advisory board participation from Novartis, Seagen, Sanova and Servier. G.M. has received honoraria from lectures, consultation or advisory board participation from Brainlab, Accuray, Servier, Novocure and AstraZeneca. A.M.S. reports trial funding from EMD Serono, ITM, Telix Pharmaceuticals, Avid Radiopharmaceuticals, Fusion Pharmaceuticals and Cyclotek (funds paid to institution), research funding from MedImmune, Avid Radiopharmaceuticals, AdAlta, Antengene, Humanigen, Telix Pharmaceuticals and Theramyc (funds paid to institution) and advisory board participation for Telix, Imagion and ImmunOs. S.C.S. has received research grant support from Blue Earth Diagnostics, CeCaVa and Apollomics and consultation or advisory board participation from Roche, Tocagen, Servier, Miltenyi, Medac and Chimerix. J.I. is a principal investigator on investigator-initiated trial grants from Novartis Pharmaceuticals, General Electric Healthcare and Curium Pharma (funds paid to institution). J.I. has received conference travel support from Siemens Healthineers. D.R.J. has received honoraria for consultation or advisory board participation from Novartis, Telix Pharmaceuticals and Cellectar Biosciences. B.S. has received honoraria for lectures and consultation from Novocure. N.T. has received honoraria for advisory board participation from Telix Pharmaceuticals and receives in-kind funding from Curium Pharma. A.V. has received honoraria for lectures and advisory board participation from Curium, Eisai, General Electric and Novartis. J.-C.T. has received reimbursement of travel expenses from Servier. E.G. has received compensation for advisory board participation from Kiyatec, Karyopharm Therapeutics, Boston Scientific, Servier Pharmaceuticals, Boehringer Ingelheim and Modifi Biosciences and research funding from Servier Pharmaceuticals (formerly Agios Pharmaceuticals) and Denovo Biopharma. P.K.B. has consulted for ElevateBio, Genentech, Angiochem, Tesaro, Axiom Healthcare Strategies, InCephalo Therapeutics, Medscape, MPM Capital Advisors, Dantari Pharmaceuticals, SK Life Science, Pfizer, CraniUS, Eli Lilly, Kazia, Sintetica, Voyager Therapeutics, Advise Connect Inspire, Merck and Atavistik, is on the scientific advisory board for CraniUS and Kazia and has received speaker’s honoraria from Genentech and Pfizer and research support (institution) from Merck, Mirati, Eli Lilly and Kinnate. P.Y.W. has received research support from AstraZeneca, Black Diamond, Bristol Myers Squibb, Chimerix, Eli Lilly, Erasca, the Global Coalition for Adaptive Research, Kazia, MediciNova, Merck, Novartis, Quadriga, Servier and VBI Vaccines and honoraria for advisory board participation or consulting from AstraZeneca, Black Diamond, Bristol Myers Squibb, Chimerix, Eli Lilly, Erasca, the Global Coalition for Adaptive Research, Kazia, MediciNova, Merck, Novartis, Quadriga, Servier and VBI Vaccines. M.W. has received research grants from Novartis, Quercis and Versameb and honoraria for lectures or advisory board participation or consulting from AnHeart, Bayer, CureVac, Medac, NeuroSense, Novartis, Novocure, Orbus, Pfizer, Philogen, Roche and Servier. N.U.L. reports institutional research support from Genentech (and Zion Pharmaceutical as part of GNE), Pfizer, Merck, Seattle Genetics (now Pfizer), Olema Pharmaceuticals and AstraZeneca, consulting honoraria from Puma, Seattle Genetics, Daiichi Sankyo, AstraZeneca, Olema Pharmaceuticals, Janssen, Blueprint Medicines, Stemline/Menarini, Artera and Eisai, royalties from UpToDate and travel support from Olema Pharmaceuticals and AstraZeneca. M.P. has received honoraria for lectures, consultation or advisory board participation from Bayer, Bristol Myers Squibb, Novartis, Gerson Lehrman Group, CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, AstraZeneca, AbbVie, Lilly, MedAhead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals and Servier as well as travel support from Servier, Daiichi Sankyo, Roche and MEDSIR.

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RANO criteria for response assessment of brain metastases based on amino acid PET imaging

Affiliations

RANO criteria for response assessment of brain metastases based on amino acid PET imaging

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

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Medical