Imaging Trials Resources

Investigators New to Clinical Trials

Investigators who are new to the conduct of clinical trials should consider identifying an appropriate mentor. They should think about how to establish the right composition for the clinical trial team (e.g., trial manager, statistician, data manager, study coordinator(s), research assistants, institutional review board [IRB] and ethics coordinator(s)). To learn more about the application submission process, visit the NCI Clinical Trials Stewardship Initiative homepage.

Phase I/II Trials

The Cancer Imaging Program has developed a contract-supported infrastructure to support phase I (Safety) and phase II (Preliminary Efficacy) clinical trials of promising imaging agents. These clinical trials will be used to rapidly evaluate the safety and diagnostic imaging capabilities of promising imaging probes, ligands, radiopharmaceuticals, and contrast agents that are of interest to NCI.

The Safety and Preliminary Efficacy Imaging Clinical Trials contracts create an infrastructure to rapidly evaluate molecularly-targeted imaging agents. These agents are used to assess therapeutic anticancer agents on their molecular targets and determine clinically relevant correlates. The objectives of this program are:

• to rapidly conduct clinical trials necessary to assess the safety of promising imaging agents;
• to rapidly conduct clinical trials necessary to assess the diagnostic imaging capabilities and preliminary efficacy of promising imaging agents;
• to characterize the molecular interactions of new molecular imaging agents with their targets through biopsies, assays, and other appropriate technologies and correlate those effects with clinically-relevant endpoints; and
• to develop new scientific insights into molecular pathways and determinants of the relationship of the targeted imaging agents to therapeutic drug response.

The major emphasis is on imaging agents which are found to be safe and provide important structural, metabolic, or molecular imaging data, which are important and useful in the management of patients with cancer. These phase I and phase II clinical trials obtain the necessary data to fulfill the Food and Drug Administration (FDA) criteria to eventually become an approved and potentially marketable imaging agent for specific imaging indications.

The studies explore promising imaging agents, and require rapid initiation, completion, and data reporting. These contracts support the ability to implement correlative studies validating the localization of the investigational imaging agents on their molecular target in tumors. Imaging agents may originate from investigators not affiliated with clinical sites.

The number of patients in each trial varies, depending on consultation with the FDA for each specific agent. The typical size for each Safety trial is approximately 10 patients. The typical size for each Preliminary Clinical Efficacy trial is estimated to be 25 patients.

The Experimental Therapeutics Clinical Trials Network (ETCTN) was created to develop new approaches to cancer treatment in early phase (phase I and phase II) experimental therapeutic clinical trials, including early clinical trials of NCI-IND agents in high priority areas of unmet medical needs. Participants collaborate with NCI staff to achieve ETCTN objectives. The NCI provides centralized support for such activities as data management, clinical trial registration, regulatory support, and Central Institutional Review Board (CIRB) review.

Resources for NCI-Sponsored Imaging Trials

Protocol component templates for NCI-held Imaging agents

• [18F] FMISO
• [18F] FLT
• [18F] FES
• [18F] DCFBC
• [89Zr]-panitumumab

CAEPRs for NCI-held imaging agents

• [18F] FMISO
• [18F] FLT
• [18F] FES
• Ferumoxytol

IND Resources for Imaging IND Agents

Other useful protocol templates

• CTEP protocol templates (for phase 1 and 2 and 3 studies, including LOIs and concept template forms)
• Templates for the Biomarker, Imaging, and Quality of Life Studies Funding Program (BIQSFP)

Additional Resources

• NCI’s National Clinical Trials Network (NCTN)
• ECOG-ACRIN: one of the funded groups in NCTN charged with the development of advanced imaging in NCTN trials
• Imaging and Radiation Oncology Core (IROC): service-oriented component of the NCTN which provides imaging-related assistance such as Quality Assurance (QA) and Quality Control (QC) to other NCTN members
• ClinicalTrials.gov: registry and results database of publicly and private supported clinical trials conducted around the world
• CCR Molecular Imaging Program
• NIH Clinical Center: Imaging Sciences Program
• Quantitative Imaging Network (QIN)

Imaging Trial Guidelines

Bone

2016: Van den Wyngaert T, Strobel K, Kampen WU, Kuwert T, van der Bruggen W, Mohan HK, Gnanasegaran G, Delgado-Bolton R, Weber WA, Beheshti M, Langsteger W, Giammarile F, Mottaghy FM, Paycha F; EANM Bone & Joint Committee and the Oncology Committee. The EANM practice guidelines for bone scintigraphy. Eur J Nucl Med Mol Imaging. 2016 Aug;43(9):1723-38. doi: 10.1007/s00259-016-3415-4. Epub 2016 Jun 4. PMID: 27262701; PMCID: PMC4932135.

2015: Beheshti M, Mottaghy FM, Paycha F, Behrendt FFF, Van den Wyngaert T, Fogelman I, Strobel K, Celli M, Fanti S, Giammarile F, Krause B, Langsteger W. (18)F-NaF PET/CT: EANM procedure guidelines for bone imaging. Eur J Nucl Med Mol Imaging. 2015 Oct;42(11):1767-1777. doi: 10.1007/s00259-015-3138-y. Epub 2015 Jul 23. Erratum in: Eur J Nucl Med Mol Imaging. 2017 Nov 13;: PMID: 26201825.

Brain

2021: Avula S, Peet A, Morana G, Morgan P, Warmuth-Metz M, Jaspan T; European Society for Paediatric Oncology (SIOPE)-Brain Tumour Imaging Group. European Society for Paediatric Oncology (SIOPE) MRI guidelines for imaging patients with central nervous system tumours. Childs Nerv Syst. 2021 Aug;37(8):2497-2508. doi: 10.1007/s00381-021-05199-4. Epub 2021 May 10. Erratum in: Childs Nerv Syst. 2021 Jul 19;: PMID: 33973057.

2019: Law I, Albert NL, Arbizu J, Boellaard R, Drzezga A, Galldiks N, la Fougère C, Langen KJ, Lopci E, Lowe V, McConathy J, Quick HH, Sattler B, Schuster DM, Tonn JC, Weller M. Joint EANM/EANO/RANO practice guidelines/SNMMI procedure standards for imaging of gliomas using PET with radiolabelled amino acids and [18F]FDG: version 1.0. Eur J Nucl Med Mol Imaging. 2019 Mar;46(3):540-557. doi: 10.1007/s00259-018-4207-9. Epub 2018 Dec 5. PMID: 30519867; PMCID: PMC6351513.

General

2021: Vali R, Alessio A, Balza R, Borgwardt L, Bar-Sever Z, Czachowski M, Jehanno N, Kurch L, Pandit-Taskar N, Parisi M, Piccardo A, Seghers V, Shulkin BL, Zucchetta P, Lim R. SNMMI Procedure Standard/EANM Practice Guideline on Pediatric 18F-FDG PET/CT for Oncology 1.0. J Nucl Med. 2021 Jan;62(1):99-110. doi: 10.2967/jnumed.120.254110. PMID: 33334912.

2015: Boellaard R, Delgado-Bolton R, Oyen WJ, Giammarile F, Tatsch K, Eschner W, Verzijlbergen FJ, Barrington SF, Pike LC, Weber WA, Stroobants S, Delbeke D, Donohoe KJ, Holbrook S, Graham MM, Testanera G, Hoekstra OS, Zijlstra J, Visser E, Hoekstra CJ, Pruim J, Willemsen A, Arends B, Kotzerke J, Bockisch A, Beyer T, Chiti A, Krause BJ; European Association of Nuclear Medicine (EANM). FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0. Eur J Nucl Med Mol Imaging. 2015 Feb;42(2):328-54. doi: 10.1007/s00259-014-2961-x. Epub 2014 Dec 2. PMID: 25452219; PMCID: PMC4315529.

Gastrointestinal

2015: Liu T, Behr S, Khan S, Osterhoff R, Aparici CM. Focal Colonic FDG Activity with PET/CT: Guidelines for Recommendation of Colonoscopy. World J Nucl Med. 2015 Jan-Apr;14(1):25-30. doi: 10.4103/1450-1147.150524. PMID: 25709541; PMCID: PMC4337003.

Lung

2017: MacMahon H, Naidich DP, Goo JM, Lee KS, Leung ANC, Mayo JR, Mehta AC, Ohno Y, Powell CA, Prokop M, Rubin GD, Schaefer-Prokop CM, Travis WD, Van Schil PE, Bankier AA. Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017. Radiology. 2017 Jul;284(1):228-243. doi: 10.1148/radiol.2017161659. Epub 2017 Feb 23. PMID: 28240562.

Melanoma

2015: Bluemel C, Herrmann K, Giammarile F, Nieweg OE, Dubreuil J, Testori A, Audisio RA, Zoras O, Lassmann M, Chakera AH, Uren R, Chondrogiannis S, Colletti PM, Rubello D. EANM practice guidelines for lymphoscintigraphy and sentinel lymph node biopsy in melanoma. Eur J Nucl Med Mol Imaging. 2015 Oct;42(11):1750-1766. doi: 10.1007/s00259-015-3135-1. Epub 2015 Jul 25. PMID: 26205952.

Radiopharmaceutical Therapy

2020: Hurwitz M, Buscombe JR, Jacene HA, Klitzke AK, Lamonica D, Lu Y, Pryma DA, Rohren EM, Speer TW, Subramaniam RM, Thompson HM, Tomblyn MB, Wong WW, Xiao Y, Banks KP, Brown RKJ. ACR-ACNM-ASTRO-SNMMI Practice Parameter for the Performance of Therapy With Radium-223. Am J Clin Oncol. 2020 Aug;43(8):539-544. doi: 10.1097/COC.0000000000000702. PMID: 32520788.

2016: Ljungberg M, Celler A, Konijnenberg MW, Eckerman KF, Dewaraja YK, Sjögreen- Gleisner K; SNMMI MIRD Committee, Bolch WE, Brill AB, Fahey F, Fisher DR, Hobbs R, Howell RW, Meredith RF, Sgouros G, Zanzonico P; EANM Dosimetry Committee, Bacher K, Chiesa C, Flux G, Lassmann M, Strigari L, Walrand S. MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative 177Lu SPECT Applied for Dosimetry of Radiopharmaceutical Therapy. J Nucl Med. 2016 Jan;57(1):151-62. doi: 10.2967/jnumed.115.159012. Epub 2015 Oct 15. PMID: 26471692.

Radiotherapy

2021: Adam JA, Loft A, Chargari C, Delgado Bolton RC, Kidd E, Schöder H, Veit-Haibach P, Vogel WV. EANM/SNMMI practice guideline for [18F]FDG PET/CT external beam radiotherapy treatment planning in uterine cervical cancer v1.0. Eur J Nucl Med Mol Imaging. 2021 Apr;48(4):1188-1199. doi: 10.1007/s00259-020-05112-2. Epub 2020 Dec 4. PMID: 33275178; PMCID: PMC8041686.

Thyroid

2018: Ha EJ, Na DG, Baek JH, Sung JY, Kim JH, Kang SY. US Fine-Needle Aspiration Biopsy for Thyroid Malignancy: Diagnostic Performance of Seven Society Guidelines Applied to 2000 Thyroid Nodules. Radiology. 2018 Jun;287(3):893-900. doi: 10.1148/radiol.2018171074. Epub 2018 Feb 21. PMID: 29465333.

Urogenital

2021: Manganaro L, Lakhman Y, Bharwani N, Gui B, Gigli S, Vinci V, Rizzo S, Kido A, Cunha TM, Sala E, Rockall A, Forstner R, Nougaret S. Staging, recurrence and follow-up of uterine cervical cancer using MRI: Updated Guidelines of the European Society of Urogenital Radiology after revised FIGO staging 2018. Eur Radiol. 2021 Apr 14. doi: 10.1007/s00330-020-07632-9. Epub ahead of print. Erratum in: Eur Radiol. 2021 Jun 17;: PMID: 33852049.

2019: Nougaret S, Horta M, Sala E, Lakhman Y, Thomassin-Naggara I, Kido A, Masselli G, Bharwani N, Sadowski E, Ertmer A, Otero-Garcia M, Kubik-Huch RA, Cunha TM, Rockall A, Forstner R. Endometrial Cancer MRI staging: Updated Guidelines of the European Society of Urogenital Radiology. Eur Radiol. 2019 Feb;29(2):792-805. doi: 10.1007/s00330-018-5515-y. Epub 2018 Jul 11. PMID: 29995239.

2011: Balleyguier C, Sala E, Da Cunha T, Bergman A, Brkljacic B, Danza F, Forstner R, Hamm B, Kubik-Huch R, Lopez C, Manfredi R, McHugo J, Oleaga L, Togashi K, Kinkel K. Staging of uterine cervical cancer with MRI: guidelines of the European Society of Urogenital Radiology. Eur Radiol. 2011 May;21(5):1102-10. doi: 10.1007/s00330-010-1998-x. Epub 2010 Nov 10. PMID: 21063710.

2018: Kubik-Huch RA, Weston M, Nougaret S, Leonhardt H, Thomassin-Naggara I, Horta M, Cunha TM, Maciel C, Rockall A, Forstner R. European Society of Urogenital Radiology (ESUR) Guidelines: MR Imaging of Leiomyomas. Eur Radiol. 2018 Aug;28(8):3125-3137. doi: 10.1007/s00330-017-5157-5. Epub 2018 Feb 28. PMID: 29492599; PMCID: PMC6028852.

Renal

2018: Ward RD, Tanaka H, Campbell SC, Remer EM. 2017 AUA Renal Mass and Localized Renal Cancer Guidelines: Imaging Implications. Radiographics. 2018 Nov-Dec;38(7):2021-2033. doi: 10.1148/rg.2018180127. Epub 2018 Oct 19. PMID: 30339517.

Prostate

2019: Afaq A, Gleeson F, Scarsbrook A, Bradley K, Subesinghe M, Macpherson R, Haroon A, Patel N, Chua S, Wong WL, Vinjamuri S, Warbey VS, Cook GJ, Bomanji J. UK guidelines on 18F-fluciclovine PET/CT in prostate cancer imaging. Nucl Med Commun. 2019 Jul;40(7):662-674. doi: 10.1097/MNM.0000000000001030. PMID: 31145206.

2017: Fendler WP, Eiber M, Beheshti M, Bomanji J, Ceci F, Cho S, Giesel F, Haberkorn U, Hope TA, Kopka K, Krause BJ, Mottaghy FM, Schöder H, Sunderland J, Wan S, Wester HJ, Fanti S, Herrmann K. 68Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2017 Jun;44(6):1014-1024. doi: 10.1007/s00259-017-3670-z. PMID: 28283702.