PSMA scan
{{see also|Gallium scan#Gallium PSMA scan}}
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.
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.{{cite journal |last1=Wang |first1=Fujin |last2=Li |first2=Zhifeng |last3=Feng |first3=Xiaoqian |last4=Yang |first4=Dazhuang |last5=Lin |first5=Mei |title=Advances in PSMA-targeted therapy for prostate cancer |journal=Prostate Cancer and Prostatic Diseases |date=March 2022 |volume=25 |issue=1 |pages=11–26 |doi=10.1038/s41391-021-00394-5 |pmid=34050265|s2cid=235241529 }}{{cite journal |last1=Mena |first1=Esther |last2=Lindenberg |first2=Liza |last3=Choyke |first3=Peter |title=The Impact of PSMA PET/CT Imaging in Prostate Cancer Radiation Treatment |journal=Seminars in Nuclear Medicine |date=March 2022 |volume=52 |issue=2 |pages=255–262 |doi=10.1053/j.semnuclmed.2021.12.008 |pmid=35016755 |pmc=8960055}}
Mechanism
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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.{{cite journal |last1=Wang |first1=He |last2=He |first2=Zhangxin |last3=Liu |first3=Xiao-Ang |last4=Huang |first4=Yuhua |last5=Hou |first5=Jianquan |last6=Zhang |first6=Weijie |last7=Ding |first7=Dan |title=Advances in Prostate-Specific Membrane Antigen (PSMA)-Targeted Phototheranostics of Prostate Cancer |journal=Small Structures |date=August 2022 |volume=3 |issue=8 |page=2200036 |doi=10.1002/sstr.202200036|s2cid=248702668 }}{{cite journal |last1=Piron |first1=Sarah |last2=Verhoeven |first2=Jeroen |last3=Vanhove |first3=Christian |last4=De Vos |first4=Filip |title=Recent advancements in 18F-labeled PSMA targeting PET radiopharmaceuticals |journal=Nuclear Medicine and Biology |date=March 2022 |volume=106-107 |pages=29–51 |doi=10.1016/j.nucmedbio.2021.12.005 |pmid=34998217|doi-access=free|hdl=1854/LU-8732924 |hdl-access=free }} 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.{{cite journal |last1=Hofman |first1=Michael S. |last2=Hicks |first2=Rodney J. |last3=Maurer |first3=Tobias |last4=Eiber |first4=Matthias |title=Prostate-specific Membrane Antigen PET: Clinical Utility in Prostate Cancer, Normal Patterns, Pearls, and Pitfalls |journal=RadioGraphics |date=January 2018 |volume=38 |issue=1 |pages=200–217 |doi=10.1148/rg.2018170108 |pmid=29320333|doi-access=free}} These ligands for PSMA-scanning target the large extracellular region of the PSMA glycoprotein.{{cite journal |last1=de Galiza Barbosa |first1=Felipe |last2=Queiroz |first2=Marcelo Araujo |last3=Nunes |first3=Rafael Fernandes |last4=Costa |first4=Larissa Bastos |last5=Zaniboni |first5=Elaine Caroline |last6=Marin |first6=José Flavio Gomes |last7=Cerri |first7=Giovanni Guido |last8=Buchpiguel |first8=Carlos Alberto |title=Nonprostatic diseases on PSMA PET imaging: a spectrum of benign and malignant findings |journal=Cancer Imaging |date=December 2020 |volume=20 |issue=1 |page=23 |doi=10.1186/s40644-020-00300-7 |pmid=32169115 |pmc=7071711|doi-access=free}}
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.{{cite journal |last1=Heidegger |first1=Isabel |last2=Kesch |first2=Claudia |last3=Kretschmer |first3=Alexander |last4=Tsaur |first4=Igor |last5=Ceci |first5=Francesco |last6=Valerio |first6=Massimo |last7=Tilki |first7=Derya |last8=Marra |first8=Giancarlo |last9=Preisser |first9=Felix |last10=Fankhauser |first10=Christian D |last11=Zattoni |first11=Fabio |last12=Chiu |first12=Peter |last13=Puche-Sanz |first13=Ignacio |last14=Olivier |first14=Jonathan |last15=van den Bergh |first15=Roderik C N |last16=Kasivisvanathan |first16=Veeru |last17=Pircher |first17=Andreas |last18=Virgolini |first18=Irene |last19=Gandaglia |first19=Giorgio |title=Biomarkers to personalize treatment with 177Lu-PSMA-617 in men with metastatic castration-resistant prostate cancer - a state of the art review |journal=Therapeutic Advances in Medical Oncology |date=January 2022 |volume=14 |page=175883592210819 |doi=10.1177/17588359221081922 |pmid=35273651 |pmc=8902011}}
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.{{cite web |title=EAU Guidelines on Prostate Cancer |url=https://uroweb.org/guidelines/prostate-cancer/chapter/introduction |website=Uroweb |publisher=European Association of Urology |access-date=8 December 2022 |language=en |date=2022}} 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.{{cite journal |last1=Trabulsi |first1=Edouard J. |last2=Rumble |first2=R. Bryan |last3=Jadvar |first3=Hossein |last4=Hope |first4=Thomas |last5=Pomper |first5=Martin |last6=Turkbey |first6=Baris |last7=Rosenkrantz |first7=Andrew B. |last8=Verma |first8=Sadhna |last9=Margolis |first9=Daniel J. |last10=Froemming |first10=Adam |last11=Oto |first11=Aytekin |last12=Purysko |first12=Andrei |last13=Milowsky |first13=Matthew I. |last14=Schlemmer |first14=Heinz-Peter |last15=Eiber |first15=Matthias |last16=Morris |first16=Michael J. |last17=Choyke |first17=Peter L. |last18=Padhani |first18=Anwar |last19=Oldan |first19=Jorge |last20=Fanti |first20=Stefano |last21=Jain |first21=Suneil |last22=Pinto |first22=Peter A. |last23=Keegan |first23=Kirk A. |last24=Porter |first24=Christopher R. |last25=Coleman |first25=Jonathan A. |last26=Bauman |first26=Glenn S. |last27=Jani |first27=Ashesh B. |last28=Kamradt |first28=Jeffrey M. |last29=Sholes |first29=Westley |last30=Vargas |first30=H. Alberto |title=Optimum Imaging Strategies for Advanced Prostate Cancer: ASCO Guideline |journal=Journal of Clinical Oncology |date=10 June 2020 |volume=38 |issue=17 |pages=1963–1996 |doi=10.1200/JCO.19.02757 |pmid=32048940|doi-access=free}} A 2024 overview of reviews published in Seminars of Nuclear Medicine concluded that while evidence gaps remain for some outcomes and most systematic reviews are at high or unclear risk of bias, the evidence base is broadly supportive of 18-F PSMA PET/CT in patients with high-risk prostate cancer or biochemical recurrence {{cite journal |author=Andrew Dullea |author2=Lydia O'Sullivan |author3=Kirsty K. O'Brien |author4=Marie Carrigan |author5=Susan Ahern |author6=Maeve McGarry |author7=Patricia Harrington |author8=Kieran A. Walsh |author9=Susan M. Smith |author10=Máirín Ryan |title= Diagnostic Accuracy of 18F-Prostate Specific Membrane Antigen (PSMA) PET/CT Radiotracers in Staging and Restaging of Patients With High-Risk Prostate Cancer or Biochemical Recurrence: An Overview of Reviews |url= https://www.sciencedirect.com/science/article/pii/S0001299824000448 |journal=Seminars in Nuclear Medicine | pmid =38906759 |doi=10.1053/j.semnuclmed.2024.05.003 | access-date = 14 January 2024|hdl=10147/642358 |hdl-access=free }}
=Radiopharmaceuticals=
Availability
In part thanks to the wide range of similar PSMA radiopharmaceuticals,{{cite journal |last1=Young |first1=Jennifer D |last2=Jauregui-Osoro |first2=Maite |last3=Wong |first3=Wai-Lup |last4=Cooper |first4=Margaret S |last5=Cook |first5=Gary |last6=Barrington |first6=Sally F |last7=Ma |first7=Michelle T |last8=Blower |first8=Philip J |last9=Aboagye |first9=Eric O |title=An overview of nuclear medicine research in the UK and the landscape for clinical adoption |journal=Nuclear Medicine Communications |date=December 2021 |volume=42 |issue=12 |pages=1301–1312 |doi=10.1097/MNM.0000000000001461 |pmid=34284442 |pmc=8584216}} 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.{{cite report |title=EAU-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer |url=https://d56bochluxqnz.cloudfront.net/documents/EAU-Guidelines-on-Prostate-Cancer-2018.pdf |publisher=European Association of Urology |access-date=23 July 2022 |date=2018}}{{cite web |title=EAU Guidelines - Prostate Cancer - Summary of Changes 2018 |url=https://uroweb.org/guidelines/prostate-cancer/summary-of-changes/2018 |website=Uroweb |publisher=European Association of Urology |access-date=23 July 2022 |language=en}}{{cite news |last1=Tagawa |first1=Scott T |last2=Bander |first2=Neil H |last3=Osborne |first3=Joseph R |title=Evaluating the Current Role of PSMA PET: Utility, Availability, and Challenges |work=ASCO Daily News |publisher=American Society of Clinical Oncology |date=2 March 2022 |doi=10.1200/ADN.22.200864|doi-access=free}}{{cite journal |last1=Fanti |first1=Stefano |last2=Goffin |first2=Karolien |last3=Hadaschik |first3=Boris A |last4=Herrmann |first4=Ken |last5=Maurer |first5=Tobias |last6=MacLennan |first6=Steven |last7=Oprea-Lager |first7=Daniela E. |last8=Oyen |first8=Wim JG |last9=Rouvière |first9=Olivier |last10=Mottet |first10=Nicolas |last11=Bjartell |first11=Anders |title=Consensus statements on PSMA PET/CT response assessment criteria in prostate cancer |journal=European Journal of Nuclear Medicine and Molecular Imaging |date=February 2021 |volume=48 |issue=2 |pages=469–476 |doi=10.1007/s00259-020-04934-4 |pmid=32617640 |pmc=7835167}}
=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.{{cite web |title=Illuccix |url=https://www.tga.gov.au/apm-summary/illuccix |website=Therapeutic Goods Administration |publisher=Australian Government Department of Health |access-date=23 July 2022 |language=en |date=24 November 2021}}
=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.{{cite web |title=Submission of European Marketing Authorisation Application |url=https://telixpharma.com/news-views/telix-submits-european-marketing-authorisation-application-for-prostate-cancer-imaging-product/ |website=Telix |access-date=23 July 2022 |language=en |date=1 May 2020}}{{cite news |title=Telix's (ASX:TLX) Illuccix EU regulatory submission progresses to final stage |url=https://themarketherald.com.au/telixs-asxtsx-illuccix-eu-regulatory-submission-progresses-to-final-stage-2021-12-10/ |work=The Market Herald |date=9 December 2021}}
In 2022 a marketing authorisation application was made by the manufacturer of 18F-DCFPyL (branded Pylclari) to the European Medicines Agency.
Polish manufacturer and distributor of radiopharmaceutical procuts, Polatom, has been granted a US patent for a 99mTc-PSMA-T4 kit.{{cite web |title=POLATOM with a patent |url=https://www.polatom.pl/2022/10/03/polatom-with-a-patent/ |website=Polatom |date=3 October 2022}}{{cite patent |country=US |number=11426395B2 |status=patent |title=PSMA inhibitor derivatives for labelling with 99mTc via HYNIC, a radiopharmaceutical kit, radiopharmaceutical preparations and their use in prostate cancer diagnostics |pubdate=2022-08-30 |gdate=2022-08-30 |fdate=2019-09-03 |pridate=2019-04-12 |inventor=Arkadiusz Eugeniusz Sikora, Michal Maurin, Antoni Wlodzimierz Jaron, Justyna Pijarowska-Kruszyna, Monika Wyczólkowska, Barbara Janota, Marcin Radzik, Piotr Garnuszek, Urszula Karczmarczyk |invent1= |invent2= |assign1=NARODOWE CENTRUM BADAN JADROWYCH OSRODEK RADIOIZOTOPOW POLATOM |assign2= |class= |url=}} In the UK, Tc-99m labelled PSMA has product authorisation but lacks funding.{{cite web |title=Review of molecular radiotherapy services in the UK |url=https://www.rcr.ac.uk/publication/review-molecular-radiotherapy-services-uk |website=The Royal College of Radiologists |publisher=RCP, IPEM, BNMS, RCR |page=25 |date=2021}}
=North America=
====Canada====
A new drug submission was made to Canada's regulator in 2021, for 68Ga-PSMA-11.{{cite web |title=Drug and Health Product Submissions Under Review (SUR): New drug submissions under review |url=https://www.canada.ca/en/health-canada/services/drug-health-product-review-approval/submissions-under-review/new-drug-submissions-under-review.html |publisher=Health Canada |access-date=23 July 2022 |date=10 March 2021}}
==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. However, the agent had poor sensitivity and saw little widespread use.
The first PET PSMA imaging agent, 68Ga-PSMA-11, was approved by the FDA in 2020.{{cite web | title=Drug Approval Package: Gallium Ga 68 PSMA-11 | website=U.S. Food and Drug Administration (FDA) | date=16 December 2020 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212642Orig1s000TOC.cfm | access-date=25 December 2020 | archive-date=26 January 2021 | archive-url=https://web.archive.org/web/20210126195616/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212642Orig1s000TOC.cfm | url-status=live }} Listed indications include suspected metastasis prior to initial treatment, and recurrence of prostate cancer (based on elevated serum prostate-specific antigen (PSA) level).{{cite web |title=Gallium Ga 68 PSMA-11 label |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212642Orig1s000lbl.pdf |website=Drugs@FDA |publisher=Food and Drug Administration |access-date=23 July 2022 |date=December 2020}} This was followed by two further 68Ga-PSMA-11 agents in 2021 and 2022 (branded Illucix and Locametz).{{cite web |title=ILLUCCIX |url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=214032 |website=Drugs@FDA |publisher=Food and Drug Administration |access-date=23 July 2022}}{{cite web |title=Drug Approval Package: LOCAMETZ |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/215841Orig1s000TOC.cfm |website=Drugs@FDA |publisher=Food and Drug Administration |access-date=23 July 2022}} Listed indications for Lucametz additionally includes selection of patients prior to 177Lu-PSMA radionuclide therapy.{{cite web |title=Locametz label |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215841s000lbl.pdf |website=Drugs@FDA |publisher=Food and Drug Administration |access-date=23 July 2022 |date=March 2022}}
An 18F-PSMA agent (18F-DCFPyL) (branded Pylarify) was approved by the FDA in 2021.{{cite web |title=Drug Approval Package: PYLARIFY |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214793Orig1s000TOC.cfm |website=Drugs@FDA |publisher=Food and Drug Administration |access-date=23 July 2022}} Indications are as for 68Ga-PSMA-11.{{cite web |title=Pylarify label |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214793Orig1s000lbl.pdf |website=Drugs@FDA |publisher=Food and Drug Administration |access-date=23 July 2022 |date=May 2021}}{{cite journal |last1=Jadvar |first1=Hossein |title=Prostate-specific Membrane Antigen PET: Standard Imaging in Prostate Cancer |journal=Radiology |date=24 May 2022 |volume=304 |issue=3 |pages=609–610 |doi=10.1148/radiol.221074 |pmid=35608452|pmc=9434807 }}
Another 18F-PSMA agent (18F-rhPSMA-7.3) (branded Posluma) was approved by the FDA in 2023.{{cite web |title=Drug Approval Package: PYLARIFY |url=https://www.https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/216023Orig1s000MultidisciplineR.pdf |website=Drugs@FDA |publisher=Food and Drug Administration |access-date=7 February 2024}}
=South America=
==Brazil==
68Ga-PSMA-11 (Illucixwas) was granted initial authorisation in 2021, with full approval expected in 2022.{{cite news |title=Grupo RPH fecha parceria para fabricação de radiofármaco no Brasil |url=https://medicinasa.com.br/grupo-rph-telix/ |work=Medicina S/A |date=16 December 2021 |language=pt-BR}}{{cite press release|title=Illuccix Granted Use Authorisation for Prostate Cancer Imaging in Brazil |url=https://www.biospace.com/article/releases/illuccix-granted-use-authorisation-for-prostate-cancer-imaging-in-brazil/ |website=BioSpace |publisher=Telix Pharmaceuticals |access-date=23 July 2022 |date=30 November 2021}}