Semin Musculoskelet Radiol 2023; 27(06): 655-660
DOI: 10.1055/s-0043-1775743
Review Article

Radiotracers in the Diagnosis of Pain: A Mini Review

Jacob Hascalovici
1   Relief Medical Group PA, New York, New York
2   Saul R. Korey Department of Neurology, The Arthur S. Abramson Department of Physical Medicine and Rehabilitation, Department of Anesthesiology, Albert Einstein College of Medicine, Bronx, New York
,
Anthony Babb
3   Lutroo Imaging LLC, Kalispell, Montana
,
Braxton A. Norwood
3   Lutroo Imaging LLC, Kalispell, Montana
› Author Affiliations

Abstract

The diagnosis and understanding of pain is challenging in clinical practice. Assessing pain relies heavily on self-reporting by patients, rendering it inherently subjective. Traditional clinical imaging methods such as computed tomography and magnetic resonance imaging can only detect anatomical abnormalities, offering limited sensitivity and specificity in identifying pain-causing conditions. Radiotracers play a vital role in molecular imaging that aims to identify abnormal biological processes at the cellular level, even in apparently normal anatomical structures. Therefore, molecular imaging is an important area of research as a prospective diagnostic modality for pain-causing pathophysiology. We present a mini review of the current knowledge base regarding radiotracers for identification of pain in vivo. We also describe radiocaine, a novel positron emission tomography imaging agent for sodium channels that has shown great potential for identifying/labeling pain-producing nerves and producing an objectively measurable pain intensity signal.



Publication History

Article published online:
07 November 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Dahlhamer J, Lucas J, Zelaya C. et al. Prevalence of chronic pain and high-impact chronic pain among adults—United States, 2016. MMWR Morb Mortal Wkly Rep 2018; 67 (36) 1001-1006
  • 2 Fillingim RB. Individual differences in pain: understanding the mosaic that makes pain personal. Pain 2017; 158 (Suppl. 01) S11-S18
  • 3 Brinjikji W, Luetmer PH, Comstock B. et al. Systematic literature review of imaging features of spinal degeneration in asymptomatic populations. AJNR Am J Neuroradiol 2015; 36 (04) 811-816
  • 4 Culvenor AG, Øiestad BE, Hart HF, Stefanik JJ, Guermazi A, Crossley KM. Prevalence of knee osteoarthritis features on magnetic resonance imaging in asymptomatic uninjured adults: a systematic review and meta-analysis. Br J Sports Med 2019; 53 (20) 1268-1278
  • 5 Pysz MA, Gambhir SS, Willmann JK. Molecular imaging: current status and emerging strategies. Clin Radiol 2010; 65 (07) 500-516
  • 6 Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell 2009; 139 (02) 267-284
  • 7 Min JJ. Molecular pain imaging by nuclear medicine: where does it stand and where is it going?. Nucl Med Mol Imaging 2016; 50 (04) 273-274
  • 8 Musafargani S, Ghosh KK, Mishra S, Mahalakshmi P, Padmanabhan P, Gulyás B. PET/MRI: a frontier in era of complementary hybrid imaging. Eur J Hybrid Imaging 2018; 2 (01) 12
  • 9 Phelps ME. Positron emission tomography provides molecular imaging of biological processes. Proc Natl Acad Sci U S A 2000; 97 (16) 9226-9233
  • 10 Phelps ME. PET: the merging of biology and imaging into molecular imaging. J Nucl Med 2000; 41 (04) 661-681
  • 11 Amen D. Brain SPECT imaging in clinical practice. Am J Psychiatry 2010; 167 (09) 1125 ; author reply 1125–1126
  • 12 Catafau AM. Brain SPECT in clinical practice. Part I: perfusion. J Nucl Med 2001; 42 (02) 259-271
  • 13 Camargo EE. Brain SPECT in neurology and psychiatry. J Nucl Med 2001; 42 (04) 611-623
  • 14 Yandrapalli SPY. SPECT Imaging. Treasure Island, FL: StatPearls Publishing; October 2022. Available at: https://www.ncbi.nlm.nih.gov/books/NBK564426/ Accessed August 28, 2023
  • 15 Oohashi M, Toshima H, Hayama K, Ogura I. Gallium-67 SPECT-CT for the evaluation of head and neck: preliminary study on maximum standardised uptake value in lesions, and in the parotid and submandibular glands. Pol J Radiol 2020; 85: e224-e229
  • 16 Bermo M, Saqr M, Hoffman H. et al. Utility of SPECT functional neuroimaging of pain. Front Psychiatry 2021; 12: 705242
  • 17 Nakabeppu Y, Nakajo M, Gushiken T, Tsuchimochi S, Tani A, Kanmura Y. Decreased perfusion of the bilateral thalami in patients with chronic pain detected by Tc-99m-ECD SPECT with statistical parametric mapping. Ann Nucl Med 2001; 15 (05) 459-463
  • 18 Nakamura Y, Nojiri K, Yoshihara H. et al. Significant differences of brain blood flow in patients with chronic low back pain and acute low back pain detected by brain SPECT. J Orthop Sci 2014; 19 (03) 384-389
  • 19 Bermo MS, Zacharias C, Patterson D. et al. The role of the cerebellum in pain perception: a brain SPECT perfusion study in patients with burn injuries. J Neuroimaging 2020; 30 (06) 815-821
  • 20 Newberg AB, Hersh EV, Levin LM. et al. Double-blind, placebo-controlled, randomized pilot study of cerebral blood flow patterns employing SPECT imaging in dental postsurgical pain patients with and without pain relief. Clin Ther 2011; 33 (12) 1894-1903
  • 21 Anzola LK, Hernandez N, Rodriguez LF. et al. The role of SPECT/CT in painful, noninfected knees after knee arthroplasty: a systematic review and meta-analysis-a diagnostic test accuracy review. J Orthop Surg Res 2023; 18 (01) 223
  • 22 Varga M, Kantorová L, Langaufová A. et al. Role of single-photon emission computed tomography imaging in the diagnosis and treatment of chronic neck or back pain caused by spinal degeneration: a systematic review. World Neurosurg 2023; 173: 65-78
  • 23 Tender GC, Davidson C, Shields J. et al. Primary pain generator identification by CT-SPECT in patients with degenerative spinal disease. Neurosurg Focus 2019; 47 (06) E18
  • 24 Kato S, Demura S, Matsubara H. et al. Utility of bone SPECT/CT to identify the primary cause of pain in elderly patients with degenerative lumbar spine disease. J Orthop Surg Res 2019; 14 (01) 185
  • 25 Torres-Ferrus M, Pareto D, Gallardo VJ. et al. Cortical metabolic and structural differences in patients with chronic migraine. An exploratory 18FDG-PET and MRI study. J Headache Pain 2021; 22 (01) 75
  • 26 Huo BB, Zheng MX, Hua XY, Shen J, Wu JJ, Xu JG. Metabolic brain network analysis with 18F-FDG PET in a rat model of neuropathic pain. Front Neurol 2021; 12: 566119
  • 27 Cui Y, Neyama H, Hu D. et al. FDG PET imaging of the pain matrix in neuropathic pain model rats. Biomedicines 2022; 11 (01) 63
  • 28 Yoder JS, Kogan F, Gold GE. Applications of PET-computed tomography-magnetic resonance in the management of benign musculoskeletal disorders. PET Clin 2019; 14 (01) 1-15
  • 29 Biswal S, Behera D, Yoon DH. et al. [18F]FDG PET/MRI of patients with chronic pain alters management: early experience. EJNMMI Phys 2015; 2 (Suppl. 01) A84
  • 30 Park PSU, Raynor WY, Sun Y, Werner TJ, Rajapakse CS, Alavi A. 18F-sodium fluoride PET as a diagnostic modality for metabolic, autoimmune, and osteogenic bone disorders: cellular mechanisms and clinical applications. Int J Mol Sci 2021; 22 (12) 6504
  • 31 Jenkins NW, Talbott JF, Shah V. et al. [18F]-sodium fluoride PET MR-based localization and quantification of bone turnover as a biomarker for facet joint-induced disability. AJNR Am J Neuroradiol 2017; 38 (10) 2028-2031
  • 32 Spirig JM, Hüllner M, Cornaz F. et al. [18F]-sodium fluoride PET/MR for painful lumbar facet joint degeneration—a randomized controlled clinical trial. Spine J 2022; 22 (05) 769-775
  • 33 Even-Sapir E, Metser U, Flusser G. et al. Assessment of malignant skeletal disease: initial experience with 18F-fluoride PET/CT and comparison between 18F-fluoride PET and 18F-fluoride PET/CT. J Nucl Med 2004; 45 (02) 272-278
  • 34 Tsai SY, Hayashi T, Mori T, Su TP. Sigma-1 receptor chaperones and diseases. Cent Nerv Syst Agents Med Chem 2009; 9 (03) 184-189
  • 35 Siddiqui T, Bhatt LK. Targeting sigma-1 receptor: a promising strategy in the treatment of Parkinson's disease. Neurochem Res 2023; May 31 (Epub ahead of print)
  • 36 Mavlyutov TA, Guo LW, Epstein ML, Ruoho AE. Role of the sigma-1 receptor in amyotrophic lateral sclerosis (ALS). J Pharmacol Sci 2015; 127 (01) 10-16
  • 37 Ryskamp DA, Korban S, Zhemkov V, Kraskovskaya N, Bezprozvanny I. Neuronal sigma-1 receptors: signaling functions and protective roles in neurodegenerative diseases. Front Neurosci 2019; 13: 862
  • 38 Sánchez-Fernández C, Entrena JM, Baeyens JM, Cobos EJ. Sigma-1 receptor antagonists: a new class of neuromodulatory analgesics. Adv Exp Med Biol 2017; 964: 109-132
  • 39 Merlos M, Romero L, Zamanillo D, Plata-Salamán C, Vela JM. Sigma-1 receptor and pain. Handb Exp Pharmacol 2017; 244: 131-161
  • 40 Lee Collier T, O'Brien JC, Waterhouse RN. Synthesis of [18F]-1-(3-Fluoropropyl)-4-(4-cyanophenoxymethyl)-piperidine: a potential sigma-1 receptor radioligand for PET. J Labelled Comp Radiopharm 1996; 38 (09) 785-794
  • 41 Waterhouse R, Nobler M, Zhou Y. et al. First evaluation of the sigma-1 receptor radioligand [18F] 1–3-fluoropropyl-4-((4-cyanophenoxy)-methyl) piperidine ([18F] FPS) in humans. Neuroimage 2004; 22: T29-T30
  • 42 Biswal S. [18F]FTC-146 PET/MRI in healthy volunteers and in CRPS and sciatica. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT02753101 Accessed August 28, 2023
  • 43 Ganjoo K. 18F-FTC-146 PET/CT in newly-diagnosed osteosarcoma. 2023. Available at: https://classic.clinicaltrials.gov/ct2/show/NCT04365660 Accessed August 28, 2023
  • 44 Hoehne A, Behera D, Parsons WH. et al. A 18F-labeled saxitoxin derivative for in vivo PET-MR imaging of voltage-gated sodium channel expression following nerve injury. J Am Chem Soc 2013; 135 (48) 18012-18015
  • 45 Goodwin G, McMahon SB. The physiological function of different voltage-gated sodium channels in pain. Nat Rev Neurosci 2021; 22 (05) 263-274
  • 46 Hooker JM, Strebl MG, Schroeder FA. et al. Imaging cardiac SCN5A using the novel F-18 radiotracer radiocaine. Sci Rep 2017; 7: 42136
  • 47 Bartolo ND, Reid SE, Krishnan HS. et al. Radiocaine: an imaging marker of neuropathic injury. ACS Chem Neurosci 2022; 13 (24) 3661-3667
  • 48 Ho Kim S, Mo Chung J. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992; 50 (03) 355-363
  • 49 National Institutes of Health. What is the NIH HEAL initiative? Available at: https://heal.nih.gov/ Accessed August 28, 2023