Onco-Imaging: improving upon FDG

Today, most PET (positron emission tomography) oncology procedures are performed using fluorodeoxyglucose (FDG). FDG-PET captures increased tissue glucose metabolism, a hallmark of many tumors. However, FDG also has shortcomings, particularly in terms of specificity. In addition, it is in general not suitable for the detection of hepatocellular carcinoma, prostate cancer or brain tumors/brain metastases.


Life Molecular Imaging’s development compounds also includes two radiotracers for potential use in cancer diagnosis. 68Ga-RM2, a peptide labeled with the radioactive isotope 68Gallium, is being investigated in clinical trials as a potential diagnostic for prostate cancer. 68Ga-RM2 is thought to be useful in improving the accurate detection and staging of primary prostate cancer and also has an upside potential in the recurrent setting (restaging) and also in other indications, e.g. for estrogen-receptor positive breast cancer, glioma and lung cancer. Several investigator-sponsored studies are ongoing exploring these indications.


Source: Journal of Nuclear Medicine Cover Image, April 1, 2016; 57(4). The cover image is artwork presented in Minamimoto et al. (2016) comparing pilot data on 68Ga-PSMA and 68Ga-RM2, two tracers with distinct biodistributions in patients with biochemically recurrent prostate cancer.


PET image series with gallium-68 RM2 wins award for best radiology image: The artwork included 68Ga-RM2 and 68Ga-PSMA-11 images related to work that was published by Dr. Andrei Iagaru (Stanford University) earlier in 2016 in the Journal of Nuclear Medicine (see cover image above). Both radiotracers were studied and compared with different imaging approaches in men with biochemically recurrent prostate cancer. The authors pointed out that distribution patterns of Ga-68-PSMA-11 and Ga-68-RM2 differed, implicating that some patients might benefit from having both scans performed.


Source: A. Iagaru, Stanford. Images are of 83-year-old man with biochemically recurrent prostate cancer based on PSA levels. 68Ga-PSMA-11 and 68Ga-RM2 PET scans detected the disease affecting the retroperitoneal lymph nodes while other PET tracers and diagnostic approaches failed.

Selected publications on 68Ga-RM2:

  • Wangerin et al. (2018) Clinical Evaluation of 68Ga-PSMA-II and 68Ga-RM2 PET Images Reconstructed With an Improved Scatter Correction Algorithm. AJR Am J Roentgenol, Jun 6:1-6. doi: 10.2214/AJR.17.19356. https://www.ncbi.nlm.nih.gov/pubmed/29873506
  • Minamimoto et al. (2018) Prospective Evaluation of 68Ga-RM2 PET/MRI in Patients with Biochemical Recurrence of Prostate Cancer and Negative Findings on Conventional Imaging. J Nucl Med, May;59(5):803-808. doi: 10.2967/jnumed.117.197624. https://www.ncbi.nlm.nih.gov/pubmed/29084827
  • Baratto et al. (2018) Prostate Cancer Theranostics Targeting Gastrin-Releasing Peptide Receptors. Mol Imaging Biol, Aug;20(4):501-509. doi: 10.1007/s11307-017-1151-1. https://www.ncbi.nlm.nih.gov/pubmed/29256046
  • Wieser et al. (2017) Diagnosis of recurrent prostate cancer with PET/CT imaging using the gastrin-releasing peptide receptor antagonist 68Ga-RM2: Preliminary results in patients with negative or inconclusive [18F]Fluoroethylcholine-PET/CT. Eur J Nucl Med Mol Imaging, Aug;44(9):1463-1472. doi: 10.1007/s00259-017-3702-8. https://www.ncbi.nlm.nih.gov/pubmed/28417160
  • Stoykow et al. Gastrin-releasing Peptide Receptor Imaging in Breast Cancer Using the Receptor Antagonist 68Ga-RM2 And PET. Theranostics 2016; 6(10): 1641-1650. http://www.thno.org/v06p1641
  • Minamimoto et al. (2016) Pilot Comparison of 68Ga-RM2 PET and 68Ga-PSMA-11 PET in Patients with Biochemically Recurrent Prostate Cancer. Journal of Nuclear Medicine, Apr;57(4):557-62. doi: 10.2967/jnumed.115.168393. http://www.ncbi.nlm.nih.gov/pubmed/26659347
  • Kähkönen et al. (2013) In vivo imaging of prostate cancer using [68Ga]-labeled bombesin analog BAY86-7548. Clinical Cancer Research, Oct 1;19(19):5434-43 http://www.ncbi.nlm.nih.gov/pubmed/23935037
  • Roivainen et al. (2013) Plasma pharmacokinetics, whole-body distribution, metabolism, and radiation dosimetry of 68Ga bombesin antagonist BAY 86-7548 in healthy men. Journal of  Nuclear Medicine, Jun;54(6):867-72. http://www.ncbi.nlm.nih.gov/pubmed/23564761
  • Mansi et al. Development of a potent DOTA-conjugated bombesin antagonist for targeting GRPr-positive tumours. Eur J Nucl Med Mol Imaging. 2011 Jan;38(1):97-107. http://www.ncbi.nlm.nih.gov/pubmed/20717822



Another PET agent for tumor imaging in early clinical studies is 18F-FSPG, a specific compound for imaging the xC- transporter activity. By providing a rate-limiting precursor, this transporter plays a key role in cancer growth and in glutathione-based redox balancing as well as detoxification of reactive oxygen species (ROS) and various chemotherapeutics. The favorable biodistribution, clearance pattern and high tumor detection rate of 18F-FSPG suggest a future role as a diagnostic in tumor patients and in other diseases with aberrant system xC- transporter activity.

Selected publications on FSPG:

  • Greenwood et al. (2019) Measurement of tumor antioxidant capacity and prediction of chemotherapy resistance in preclinical models of ovarian cancer by positron emission tomography. Clin Cancer Res. (online first)
  • Cheng et al. (2019) Prospective comparison of (4S)-4-(3-18F-fluoropropyl)-L-glutamate versus 18F-fluorodeoxyglucose PET/CT for detecting metastases from pancreatic ductal adenocarcinoma: a proof-of-concept study. Eur J Nucl Med Mol Imaging. (online first)
  • McCormick et al. (2018) Assessment of tumor redox status through (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid positron emission tomography imaging of system xc- activity. Cancer Res. (online first)
  • Hoehne et al. [18F]FSPG-PET reveals increased cystine/glutamate antiporter (xc-) activity in a mouse model of multiple sclerosis. J Neuroinflammation. 2018 Feb 22;15(1):55.
  • Magarik et al. Intracardiac Metastases Detected by 18F-FSPG PET/CT. Clin Nucl Med. 43(1):28-30.
  • Kavanaugh et al. (2016) Utility of [18F]FSPG PET to Image Hepatocellular Carcinoma: First Clinical Evaluation in a US Population. Molecular Imaging and Biology. 2016 Dec;18(6):924-934. https://www.ncbi.nlm.nih.gov/pubmed/27677886
  • Mittra et al. (2016) Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies. PLoS One, Feb 18;11(2):e0148628. doi: 10.1371/journal.pone.0148628. http://www.ncbi.nlm.nih.gov/pubmed/26890637
  • Mosci et al. (2016) Characterization of Physiologic (18)F FSPG Uptake in Healthy Volunteers. Radiology, Jun;279(3):898-905. doi: 10.1148/radiol.2015142000. http://www.ncbi.nlm.nih.gov/pubmed/26785040
  • Chae et al. (2016) Exploratory Clinical Investigation of (4S)-4-(3-18F-Fluoropropyl)-L-Glutamate PET of Inflammatory and Infectious Lesions. Journal of Nuclear Medicine, Jan;57(1):67-9. http://www.ncbi.nlm.nih.gov/pubmed/26471694
  • Smolarz et al. (2013) (S)-4-(3-18F-fluoropropyl)-L-glutamic acid: an 18F-labeled tumor-specific probe for PET/CT imaging–dosimetry. Journal of Nuclear Medicine, Jun;54(6):861-6. http://www.ncbi.nlm.nih.gov/pubmed/23568366
  • Baek et al. (2013) (4S)-4-(3-18F-fluoropropyl)-L-glutamate for imaging of xC transporter activity in hepatocellular carcinoma using PET: preclinical and exploratory clinical studies. Journal of Nuclear Medicine, Jan;54(1):117-23. http://www.ncbi.nlm.nih.gov/pubmed/23232273
  • Baek et al. (2012) Exploratory clinical trial of (4S)-4-(3-[18F]fluoropropyl)-L-glutamate for imaging xC- transporter using positron emission tomography in patients with non-small cell lung or breast cancer. Clinical Cancer Research, Oct 1;18(19):5427-37. http://www.ncbi.nlm.nih.gov/pubmed/22893629
  • Koglin et al. (2011) Specific PET imaging of xC- transporter activity using a ¹8F-labeled glutamate derivative reveals a dominant pathway in tumor metabolism. Clinical Cancer Research, Sep 15;17(18):6000-11. http://www.ncbi.nlm.nih.gov/pubmed/21750203