PSMA scan

Last updated

A PSMA scan is a nuclear medicine imaging technique used in the diagnosis and staging of prostate cancer. It is carried out by injection of a radiopharmaceutical with a positron or gamma emitting radionuclide and a prostate-specific membrane antigen (PSMA) targeting ligand. After injection, imaging of positron emitters such as gallium-68 (68Ga), copper-64 (64Cu), and fluorine-18 (18F) is carried out with a positron emission tomography (PET) scanner. For gamma emitters such as technetium-99m (99mTc) and indium-111 (111In) single-photon emission computed tomography (SPECT) imaging is performed with a gamma camera.

Contents

As well as the diagnosis and staging of prostate cancer, PSMA imaging can also be used to assess suitability for and plan treatment with external beam radiotherapy and PSMA-targeted radionuclide therapy. [1] [2]

Mechanism

PSMA expression and radiotracer uptake.png
PSMA expression and radiotracer uptake in prostate cancer

Attempts have been made to target the overexpression of PSMA in prostate cancer cells for several decades, although PSMA is also found in other tissue. PSMA targeting molecules have included antibodies, aptamers, peptides, and small-molecule inhibitors. [3] [4] Initially, development focussed on the antibody capromab. Later research has focussed on small molecule ligands that bind to the extracellular active centre of PSMA, such as PSMA-11. [5] These ligands for PSMA-scanning target the large extracellular region of the PSMA glycoprotein. [6]

PSMA however is also over-expressed in non prostate cancer cells, including kidney, salivary gland, lacrimal gland and duodenal mucosa, where physiological uptake may be seen on imaging. [7]

Clinical use

European Association of Urology (EAU) guidelines recognise that PSMA can provide accurate staging, however there is a lack of outcome data to inform further management. [8] The American Society of Clinical Oncology (ASCO) guidelines for imaging of advanced prostate cancer also recommend PSMA imaging (among other PET radiopharmaceuticals), while acknowledging that these are not FDA approved and therefore limited to a clinical trial or other controlled research setting. [9]

Radiopharmaceuticals

RadionuclideName INN Brand name(s)FDA approvalEMA approvalReferences
18FDCFPyLPIFLUFOLASTAT F-18PylarifyYes [10]
18FPSMA-1007
68GaPSMA-11Gallium (68Ga) gozetotide
  • Illucix
  • Locametz
  • Illucixwas
YesYes [3]
68GaTHP-PSMAGallium (68Ga) gozetotideGalliProst [11]
99mTcPSMA-11
99mTciPSMATLX599-CDx [12]
111Incapromab pendetideProstascintYes [13]
111InPSMA-I&T [3]

Availability

In part thanks to the wide range of similar PSMA radiopharmaceuticals, [4] [14] approval by regulatory authorities is at varying stages. Even so, use has been widespread in some areas, particularly as part of clinical trials. For example, European Association of Urology (EAU) guidelines have included recommendations to perform PSMA PET scans in certain circumstances since 2018, and there has been widespread agreement of the utility of PSMA scanning for several years. [15] [16] [17] [18]

Oceania

Australia

A kit for manufacture of a 68Ga-PSMA-11 product, branded Illucix, was approved by Australia's Therapeutic Goods Administration (TGA) in 2021. [19]

Europe

A marketing authorisation application for 68Ga-PSMA-11 (INN Gallium (68Ga) gozetotide), under the brand name Illucix, was made to the Danish Medicines Agency, on behalf of several EU countries and the UK. Approval is expected in 2022. [20] [21]

In 2022 a marketing authorisation application was made by the manufacturer of 18F-DCFPyL (branded Pylarify) to the European Medicines Agency. [22]

Polish manufacturer and distributor of radiopharmaceutical procuts, Polatom, has been granted a US patent for a 99mTc-PSMA-T4 kit. [23] [24] In the UK, Tc-99m labelled PSMA has product authorisation but lacks funding. [25]

North America

Canada

A new drug submission was made to Canada's regulator in 2021, for 68Ga-PSMA-11. [26]

United States

The first approved PSMA imaging agent was indium-111 (111In) capromab pendetide (branded Prostascint). It received Food and Drug Administration (FDA) approval in 1996. [13] However, the agent had poor sensitivity and saw little widespread use. [17]

The first PET PSMA imaging agent, 68Ga-PSMA-11, was approved by the FDA in 2020. [27] Listed indications include suspected metastasis prior to initial treatment, and recurrence of prostate cancer (based on elevated serum prostate-specific antigen (PSA) level). [28] This was followed by two further 68Ga-PSMA-11 agents in 2021 and 2022 (branded Illucix and Locametz). [29] [30] Listed indications for Lucametz additionally includes selection of patients prior to 177Lu-PSMA radionuclide therapy. [31]

An 18F-PSMA agent (18F-DCFPyL) was approved by the FDA in 2021. [32] Indications are as for 68Ga-PSMA-11. [33] [34]

South America

Brazil

68Ga-PSMA-11 (Illucixwas) was granted initial authorisation in 2021, with full approval expected in 2022. [35] [36]

Related Research Articles

<span class="mw-page-title-main">Nuclear medicine</span> Medical specialty

Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is "radiology done inside out" because it records radiation emitted from within the body rather than radiation that is transmitted through the body from external sources like X-ray generators. In addition, nuclear medicine scans differ from radiology, as the emphasis is not on imaging anatomy, but on the function. For such reason, it is called a physiological imaging modality. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) scans are the two most common imaging modalities in nuclear medicine.

<span class="mw-page-title-main">Bone scintigraphy</span> Nuclear medicine imaging technique

A bone scan or bone scintigraphy is a nuclear medicine imaging technique of the bone. It can help diagnose a number of bone conditions, including cancer of the bone or metastasis, location of bone inflammation and fractures, and bone infection (osteomyelitis).

Prostate cancer screening is the screening process used to detect undiagnosed prostate cancer in men without signs or symptoms. When abnormal prostate tissue or cancer is found early, it may be easier to treat and cure, but it is unclear if early detection reduces mortality rates.

<span class="mw-page-title-main">Fluorine-18</span> Isotope of fluorine emitting a positron

Fluorine-18 (18F) is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380(6) u and its half-life is 109.771(20) minutes. It decays by positron emission 96% of the time and electron capture 4% of the time. Both modes of decay yield stable oxygen-18.

A gallium scan is a type of nuclear medicine test that uses either a gallium-67 (67Ga) or gallium-68 (68Ga) radiopharmaceutical to obtain images of a specific type of tissue, or disease state of tissue. Gallium salts like gallium citrate and gallium nitrate may be used. The form of salt is not important, since it is the freely dissolved gallium ion Ga3+ which is active. Both 67Ga and 68Ga salts have similar uptake mechanisms. Gallium can also be used in other forms, for example 68Ga-PSMA is used for cancer imaging. The gamma emission of gallium-67 is imaged by a gamma camera, while the positron emission of gallium-68 is imaged by positron emission tomography (PET).

<span class="mw-page-title-main">Glutamate carboxypeptidase II</span> Enzyme

Glutamate carboxypeptidase II (GCPII), also known as N-acetyl-L-aspartyl-L-glutamate peptidase I, NAAG peptidase, or prostate-specific membrane antigen (PSMA) is an enzyme that in humans is encoded by the FOLH1 gene. Human GCPII contains 750 amino acids and weighs approximately 84 kDa.

Copper-64 (64Cu) is a positron and beta emitting isotope of copper, with applications for molecular radiotherapy and positron emission tomography. Its unusually long half-life (12.7-hours) for a positron-emitting isotope makes it increasingly useful when attached to various ligands, for PET and PET-CT scanning.

<span class="mw-page-title-main">Iobenguane</span> Chemical compound

Iobenguane, or MIBG, is an aralkylguanidine analog of the adrenergic neurotransmitter norepinephrine (noradrenaline), typically used as a radiopharmaceutical. It acts as a blocking agent for adrenergic neurons. When radiolabeled, it can be used in nuclear medicinal diagnostic and therapy techniques as well as in neuroendocrine chemotherapy treatments.

<span class="mw-page-title-main">DOTA-TATE</span> Eight amino-acid long peptide covalently bonded to a DOTA chelator

DOTA-TATE is an eight amino acid long peptide, with a covalently bonded DOTA bifunctional chelator.

Florbetapir (18F), sold under the brand name Amyvid, is a PET scanning radiopharmaceutical compound containing the radionuclide fluorine-18 that was approved for use in the United States in 2012, as a diagnostic tool for Alzheimer's disease. Florbetapir, like Pittsburgh compound B (PiB), binds to beta-amyloid, however fluorine-18 has a half-life of 109.75 minutes, in contrast to PiB's radioactive half life of 20 minutes. Wong et al. found that the longer life allowed the tracer to accumulate significantly more in the brains of people with AD, particularly in the regions known to be associated with beta-amyloid deposits.

Advanced Accelerator Applications is a France-based pharmaceutical group, specialized in the field of nuclear medicine. The group operates in all three segments of nuclear medicine to diagnose and treat serious conditions in the fields of oncology, neurology, cardiology, infectious and inflammatory diseases.

Fluciclovine (<sup>18</sup>F) Chemical compound

Fluciclovine (18F), also known as anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid, or as Axumin, is a diagnostic agent indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated prostate specific antigen (PSA) levels.

Sandip Basu is an Indian physician of Nuclear Medicine and the Head, Nuclear Medicine Academic Program at the Radiation Medicine Centre. He is also the Dean-Academic (Health-Sciences), BARC at Homi Bhabha National Institute and is known for his services and research in Nuclear Medicine, particularly on Positron emission tomography diagnostics and Targeted Radionuclide Therapy in Cancer. The Council of Scientific and Industrial Research, the apex agency of the Government of India for scientific research, awarded him the Shanti Swarup Bhatnagar Prize for Science and Technology, one of the highest Indian science awards for his contributions to Nuclear Medicine in 2012.

<span class="mw-page-title-main">Peptide receptor radionuclide therapy</span> Type of radiotherapy

Peptide receptor radionuclide therapy (PRRT) is a type of radionuclide therapy, using a radiopharmaceutical that targets peptide receptors to deliver localised treatment, typically for neuroendocrine tumours (NETs).

Flortaucipir (<sup>18</sup>F) Chemical compound

Flortaucipir (18F), sold under the brand name Tauvid, is a radioactive diagnostic agent indicated for use with positron emission tomography (PET) imaging to image the brain.

<span class="mw-page-title-main">Piflufolastat F-18</span> Chemical compound

Piflufolastat F-18, sold under the brand name Pylarify among others, is a radioactive diagnostic agent used for positron emission tomography (PET) imaging. It is given by intravenous injection.

Gallium (<sup>68</sup>Ga) gozetotide Radiopharmaceutical medication

Gallium (68Ga) gozetotide or Gallium (68Ga) PSMA-11 sold under the brand name Illuccix among others, is a radiopharmaceutical made of 68Ga conjugated to prostate-specific membrane antigen (PSMA) targeting ligand, Glu-Urea-Lys(Ahx)-HBED-CC, used for imaging prostate cancer by positron emission tomography (PET). The PSMA targeting ligand specifically directs the radiolabeled imaging agent towards the prostate cancerous lesions in men.

Lutetium (<sup>177</sup>Lu) vipivotide tetraxetan Radiopharmaceutical medication

Lutetium (177Lu) vipivotide tetraxetan, sold under the brand name Pluvicto, is a radiopharmaceutical medication used for the treatment of prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). Lutetium (177Lu) vipivotide tetraxetan is a targeted radioligand therapy.

Flotufolastat F-18, sold under the brand name Posluma, is a radioactive diagnostic agent for use with positron emission tomography (PET) imaging for prostate cancer. The active ingredient is flotufolastat F-18 gallium.

References

  1. ↑ Wang, Fujin; Li, Zhifeng; Feng, Xiaoqian; Yang, Dazhuang; Lin, Mei (March 2022). "Advances in PSMA-targeted therapy for prostate cancer". Prostate Cancer and Prostatic Diseases. 25 (1): 11–26. doi:10.1038/s41391-021-00394-5. PMID   34050265. S2CID   235241529.
  2. ↑ Mena, Esther; Lindenberg, Liza; Choyke, Peter (March 2022). "The Impact of PSMA PET/CT Imaging in Prostate Cancer Radiation Treatment". Seminars in Nuclear Medicine. 52 (2): 255–262. doi:10.1053/j.semnuclmed.2021.12.008. PMC   8960055 . PMID   35016755.
  3. 1 2 3 Wang, He; He, Zhangxin; Liu, Xiao-Ang; Huang, Yuhua; Hou, Jianquan; Zhang, Weijie; Ding, Dan (August 2022). "Advances in Prostate‐Specific Membrane Antigen (PSMA)‐Targeted Phototheranostics of Prostate Cancer". Small Structures. 3 (8): 2200036. doi:10.1002/sstr.202200036. S2CID   248702668.
  4. 1 2 Piron, Sarah; Verhoeven, Jeroen; Vanhove, Christian; De Vos, Filip (March 2022). "Recent advancements in 18F-labeled PSMA targeting PET radiopharmaceuticals". Nuclear Medicine and Biology. 106–107: 29–51. doi: 10.1016/j.nucmedbio.2021.12.005 . hdl: 1854/LU-8732924 . PMID   34998217.
  5. ↑ Hofman, Michael S.; Hicks, Rodney J.; Maurer, Tobias; Eiber, Matthias (January 2018). "Prostate-specific Membrane Antigen PET: Clinical Utility in Prostate Cancer, Normal Patterns, Pearls, and Pitfalls". RadioGraphics. 38 (1): 200–217. doi: 10.1148/rg.2018170108 . PMID   29320333.
  6. ↑ de Galiza Barbosa, Felipe; Queiroz, Marcelo Araujo; Nunes, Rafael Fernandes; Costa, Larissa Bastos; Zaniboni, Elaine Caroline; Marin, José Flavio Gomes; Cerri, Giovanni Guido; Buchpiguel, Carlos Alberto (December 2020). "Nonprostatic diseases on PSMA PET imaging: a spectrum of benign and malignant findings". Cancer Imaging. 20 (1): 23. doi: 10.1186/s40644-020-00300-7 . PMC   7071711 . PMID   32169115.
  7. ↑ Heidegger, Isabel; Kesch, Claudia; Kretschmer, Alexander; Tsaur, Igor; Ceci, Francesco; Valerio, Massimo; Tilki, Derya; Marra, Giancarlo; Preisser, Felix; Fankhauser, Christian D; Zattoni, Fabio; Chiu, Peter; Puche-Sanz, Ignacio; Olivier, Jonathan; van den Bergh, Roderik C N; Kasivisvanathan, Veeru; Pircher, Andreas; Virgolini, Irene; Gandaglia, Giorgio (January 2022). "Biomarkers to personalize treatment with 177Lu-PSMA-617 in men with metastatic castration-resistant prostate cancer - a state of the art review". Therapeutic Advances in Medical Oncology. 14: 175883592210819. doi:10.1177/17588359221081922. PMC   8902011 . PMID   35273651.
  8. ↑ "EAU Guidelines on Prostate Cancer". Uroweb. European Association of Urology. 2022. Retrieved 8 December 2022.
  9. ↑ Trabulsi, Edouard J.; Rumble, R. Bryan; Jadvar, Hossein; Hope, Thomas; Pomper, Martin; Turkbey, Baris; Rosenkrantz, Andrew B.; Verma, Sadhna; Margolis, Daniel J.; Froemming, Adam; Oto, Aytekin; Purysko, Andrei; Milowsky, Matthew I.; Schlemmer, Heinz-Peter; Eiber, Matthias; Morris, Michael J.; Choyke, Peter L.; Padhani, Anwar; Oldan, Jorge; Fanti, Stefano; Jain, Suneil; Pinto, Peter A.; Keegan, Kirk A.; Porter, Christopher R.; Coleman, Jonathan A.; Bauman, Glenn S.; Jani, Ashesh B.; Kamradt, Jeffrey M.; Sholes, Westley; Vargas, H. Alberto (10 June 2020). "Optimum Imaging Strategies for Advanced Prostate Cancer: ASCO Guideline". Journal of Clinical Oncology. 38 (17): 1963–1996. doi: 10.1200/JCO.19.02757 . PMID   32048940.
  10. ↑ "PSMA Radiopharmaceutical Effective against Prostate Cancer". National Cancer Institute . National Institutes of Health. 29 June 2021.
  11. ↑ Neels, Oliver C; Kopka, Klaus; Liolios, Christos; Afshar-Oromieh, Ali (13 December 2021). "Radiolabeled PSMA Inhibitors". Cancers. 13 (24): 6255. doi: 10.3390/cancers13246255 . PMC   8699044 . PMID   34944875.
  12. ↑ Ferro-Flores, Guillermina; Luna-Gutiérrez, Myrna; Ocampo-García, Blanca; Santos-Cuevas, Clara; Azorín-Vega, Erika; Jiménez-Mancilla, Nallely; Orocio-Rodríguez, Emmanuel; Davanzo, Jenny; García-Pérez, Francisco O (May 2017). "Clinical translation of a PSMA inhibitor for 99m Tc-based SPECT". Nuclear Medicine and Biology. 48: 36–44. doi:10.1016/j.nucmedbio.2017.01.012. PMID   28193503.
  13. 1 2 "PROSTASCINT". Drugs@FDA. Food and Drug Administration . Retrieved 19 January 2023.
  14. ↑ Young, Jennifer D; Jauregui-Osoro, Maite; Wong, Wai-Lup; Cooper, Margaret S; Cook, Gary; Barrington, Sally F; Ma, Michelle T; Blower, Philip J; Aboagye, Eric O (December 2021). "An overview of nuclear medicine research in the UK and the landscape for clinical adoption". Nuclear Medicine Communications. 42 (12): 1301–1312. doi:10.1097/MNM.0000000000001461. PMC   8584216 . PMID   34284442.
  15. ↑ EAU-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer (PDF) (Report). European Association of Urology. 2018. Retrieved 23 July 2022.
  16. ↑ "EAU Guidelines - Prostate Cancer - Summary of Changes 2018". Uroweb. European Association of Urology . Retrieved 23 July 2022.
  17. 1 2 Tagawa, Scott T; Bander, Neil H; Osborne, Joseph R (2 March 2022). "Evaluating the Current Role of PSMA PET: Utility, Availability, and Challenges". ASCO Daily News. American Society of Clinical Oncology. doi: 10.1200/ADN.22.200864 .
  18. ↑ Fanti, Stefano; Goffin, Karolien; Hadaschik, Boris A; Herrmann, Ken; Maurer, Tobias; MacLennan, Steven; Oprea-Lager, Daniela E.; Oyen, Wim JG; Rouvière, Olivier; Mottet, Nicolas; Bjartell, Anders (February 2021). "Consensus statements on PSMA PET/CT response assessment criteria in prostate cancer". European Journal of Nuclear Medicine and Molecular Imaging. 48 (2): 469–476. doi:10.1007/s00259-020-04934-4. PMC   7835167 . PMID   32617640.
  19. ↑ "Illuccix". Therapeutic Goods Administration. Australian Government Department of Health. 24 November 2021. Retrieved 23 July 2022.
  20. ↑ "Submission of European Marketing Authorisation Application". Telix. 1 May 2020. Retrieved 23 July 2022.
  21. ↑ "Telix's (ASX:TLX) Illuccix EU regulatory submission progresses to final stage". The Market Herald. 9 December 2021.
  22. ↑ "Curium Announces The Submission Of Its Marketing Authorization Application For [18F]-DCFPyL To The European Medicines Agency" (Press release). Curium. 27 June 2022.
  23. ↑ "POLATOM with a patent". Polatom. 3 October 2022.
  24. ↑ USpatent 11426395B2,Arkadiusz Eugeniusz Sikora,Michal Maurin,Antoni Wlodzimierz Jaron,Justyna Pijarowska-Kruszyna,Monika Wyczólkowska,Barbara Janota,Marcin Radzik,Piotr Garnuszek,Urszula Karczmarczyk,"PSMA inhibitor derivatives for labelling with 99mTc via HYNIC, a radiopharmaceutical kit, radiopharmaceutical preparations and their use in prostate cancer diagnostics",published 2022-08-30,issued 2022-08-30, assigned to NARODOWE CENTRUM BADAN JADROWYCH OSRODEK RADIOIZOTOPOW POLATOM
  25. ↑ "Review of molecular radiotherapy services in the UK". The Royal College of Radiologists . RCP, IPEM, BNMS, RCR. 2021. p. 25.
  26. ↑ "Drug and Health Product Submissions Under Review (SUR): New drug submissions under review". Health Canada. 10 March 2021. Retrieved 23 July 2022.
  27. ↑ "Drug Approval Package: Gallium Ga 68 PSMA-11". U.S. Food and Drug Administration (FDA). 16 December 2020. Archived from the original on 26 January 2021. Retrieved 25 December 2020.
  28. ↑ "Gallium Ga 68 PSMA-11 label" (PDF). Drugs@FDA. Food and Drug Administration. December 2020. Retrieved 23 July 2022.
  29. ↑ "ILLUCCIX". Drugs@FDA. Food and Drug Administration. Retrieved 23 July 2022.
  30. ↑ "Drug Approval Package: LOCAMETZ". Drugs@FDA. Food and Drug Administration . Retrieved 23 July 2022.
  31. ↑ "Locametz label" (PDF). Drugs@FDA. Food and Drug Administration. March 2022. Retrieved 23 July 2022.
  32. ↑ "Drug Approval Package: PYLARIFY". Drugs@FDA. Food and Drug Administration . Retrieved 23 July 2022.
  33. ↑ "Pylarify label" (PDF). Drugs@FDA. Food and Drug Administration. May 2021. Retrieved 23 July 2022.
  34. ↑ Jadvar, Hossein (24 May 2022). "Prostate-specific Membrane Antigen PET: Standard Imaging in Prostate Cancer". Radiology. 304 (3): 609–610. doi:10.1148/radiol.221074. PMC   9434807 . PMID   35608452.
  35. ↑ "Grupo RPH fecha parceria para fabricação de radiofármaco no Brasil". Medicina S/A (in Brazilian Portuguese). 16 December 2021.
  36. ↑ "Illuccix Granted Use Authorisation for Prostate Cancer Imaging in Brazil". BioSpace (Press release). Telix Pharmaceuticals. 30 November 2021. Retrieved 23 July 2022.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.