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13 november 2023: Bron:  2023 Jul;5(4):e22015

Theranostiek, een vorm van radiotherapie waarbij een specifiek stofje wordt ingebracht dat alleen de tumorcellen opzoekt en vernietigt en de gezonde cellen ongemoeid laat wordt al succesvol toegepast bij prostaatkanker via lutetium 177 en schildklierkanker via radioactief jodium, maar wordt nu ook onderzocht om te gebruiken als behandeling bij borstkankerpatiënten met uitzaaiingen.

Bij theranostiek wordt een stofje radioactief gemaakt een zogeheten radiotracer. De radiotracers worden in het lichaam ingebracht en hechten zich aan specifieke eiwitten die alleen voorkomen op kankercellen. Die radiotracer is als het ware een specifieke sleutel die alleen past op die eiwitten aan de buitenkant van de kankercellen.
Deze radiotracers met hun radioactieve materiaal vernietigen de kankercellen maar sparen de gezonde cellen die onaangetast blijven.

Zie dit schema in Figure 1:

Radionuclide therapy schematic. A radionuclide held in a chelator or cage or bound covalently is attached to a vector by a linker molecule. The vector binds to a molecular target to enable visualization of the target for diagnostic or treatment purposes and selective delivery of radiation therapy to the target. Alternatively, a free radionuclide ion can, in some circumstances, be used to target tumors or cancer cells, as with iodine 131, alastine 211, and radium 223. Created with BioRender.com.
 

Radionuclide therapy schematic. A radionuclide held in a chelator or cage or bound covalently is attached to a vector by a linker molecule. The vector binds to a molecular target to enable visualization of the target for diagnostic or treatment purposes and selective delivery of radiation therapy to the target. Alternatively, a free radionuclide ion can, in some circumstances, be used to target tumors or cancer cells, as with iodine 131, alastine 211, and radium 223. Created with BioRender.com.


Een theranostieke behandeling heeft dus veel minder bijwerkingen in vergelijking met chemotherapie en gewone radiotherapie / bestraling. Met theranostiek kunnen onderzoekers dus ook de kankercellen detecteren, specifiek bestralen en achteraf controleren of de behandeling effectief was. Maar dan hebben ze wel de specifieke eiwitten nodig van de buitenkant van de tumorcellen. Volgens prof. dr. Dalm van het Erasmus MC hebben vormen van borstkanker enkele van die specifieke eiwitten en dus zouden die geschikt zijn voor theranostiek. Zij heeft ook voor theranostiek bij prostaatkanker een prijs gewonnen en al veel onderzoek gedaan naar met name theranostiek, zie deze studies. 

O.a. deze studie is interessant: 

Combination Therapy, a Promising Approach to Enhance the Efficacy of Radionuclide and Targeted Radionuclide Therapy of Prostate and Breast Cancer


Er wordt ook al onderzoek gedaan met theranostiek met nanodeeltjes dat doordringt tot de DNA van de tumorcel in bv Leuven, zie deze studieopzet. Matthias D'Huyvetter heeft ook al verschillende studies gedaan met theranostiek, zie deze studies onder publicaties. 

Zie ook dit schema van theranostiek met nanodeeltjes in Figure 2:

Targeted -particle therapy schematic. The radionuclide therapy is intravenously infused and binds to the tumor through a vector linked to the radionuclide. While bound to the tumor, -particle emission occurs, selectively delivering radiation to the tumor. Particles are more cytotoxic than particles because they cause irreparable double-strand DNA breaks, resulting in cell death. Created with BioRender.com.

Targeted α-particle therapy schematic. The radionuclide therapy is intravenously infused and binds to the tumor through a vector linked to the radionuclide. While bound to the tumor, α-particle emission occurs, selectively delivering radiation to the tumor. α Particles are more cytotoxic than β particles because they cause irreparable double-strand DNA breaks, resulting in cell death. Created with BioRender.com.



Een reviewstudie uit juli 2023 over theranostiek is deze onderstaande reviewstudie uit juli 2023 en is als volledig studierapport gratis in te zien of te downloaden. Het studierapport beschrijft de belangrijkste vormen van theranostiek bij verschillende vormen van kanker met ook een interessante referentielijst van 94 studies en vooral ook mooie grafieken hoe een en ander in zijn werk gaat:
 2023 Jul; 5(4): e220157.
Published online 2023 Jul 21. doi: 10.1148/rycan.220157
PMCID: PMC10413300
PMID: 37477566

A Review of Theranostics: Perspectives on Emerging Approaches and Clinical Advancements

Brian J. Burkett, MD, MPH,corresponding author David J. Bartlett, MD, Patrick W. McGarrah, MD, Akeem R. Lewis, MD, Derek R. Johnson, MD, Kezban Berberoğlu, MD, Mukesh K. Pandey, PhD, Annie T. Packard, MD, Thorvardur R. Halfdanarson, MD, Carrie B. Hruska, PhD, Geoffrey B. Johnson, MD, PhD, and A. Tuba Kendi, MD
Author information Article notes Copyright and License information PMC Disclaimer

Abstract

Theranostics is the combination of two approaches—diagnostics and therapeutics—applied for decades in cancer imaging using radiopharmaceuticals or paired radiopharmaceuticals to image and selectively treat various cancers. The clinical use of theranostics has increased in recent years, with U.S. Food and Drug Administration (FDA) approval of lutetium 177 (177Lu) tetraazacyclododecane tetraacetic acid octreotate (DOTATATE) and 177Lu–prostate-specific membrane antigen vector-based radionuclide therapies. The field of theranostics has imminent potential for emerging clinical applications. This article reviews critical areas of active clinical advancement in theranostics, including forthcoming clinical trials advancing FDA-approved and emerging radiopharmaceuticals, approaches to dosimetry calculations, imaging of different radionuclide therapies, expanded indications for currently used theranostic agents to treat a broader array of cancers, and emerging ideas in the field.

Summary

Emerging approaches to theranostics, including investigational radiopharmaceuticals, expanded indications for current radionuclide therapies, and posttreatment imaging, are active areas of innovation with potential to transform clinical practice.

Essentials

  • ■ Theranostics is a concept related to radionuclide therapy that specifically refers to the use of a pair of radiopharmaceutical agents containing radionuclides used for imaging (diagnostics) and/or therapy (therapeutics).
  • ■ α Particles have high linear energy transfer and enable increased precision in radiation delivery, which theoretically decreases collateral damage to adjacent healthy tissues and may facilitate more focused targeting of small tumors and micrometastasis relative to the same dose of β-particle emitters required to achieve similar cytotoxic effects.
  • ■ The imaging of theranostic agents can potentially serve multiple independent purposes, including patient selection for therapy, confirmation of delivery to tumors, dosimetry calculation, and treatment response assessment.
  • ■ Both tetraazacyclododecane tetraacetic acid octreotate (or, DOTATATE)– and prostate-specific membrane antigen–coupled agents that now have regulatory approval for clinical use in neuroendocrine tumors and prostate cancer, respectively, are being investigated for expanded indications in other tumor classes.

Conclusion

In this review, we summarized various theranostic radiopharmaceuticals and their clinical use against a variety of cancers. Overall, theranostics for cancer imaging and treatment is rapidly evolving. Various emerging molecular targets and radiopharmaceuticals with different forms of radiation emission, such as α-emitting therapies, have a high potential to emerge as next-generation theranostics. Current and continued efforts to better estimate the dosimetry of therapeutic radiopharmaceuticals and quantify and monitor treatment response are necessary steps in the direction of individualized precision medicine for theranostics. Additional work will be needed to refine the role of radionuclide therapy in combination with other modalities of cancer treatment.

Authors declared no funding for this work.

Disclosures of conflicts of interest: B.J.B. Member of Radiology: Imaging Cancer trainee editorial board. D.J.B. Patent pending for a radiopharmaceutical for imaging and therapy. P.W.M. No relevant relationships. A.R.L. No relevant relationships. D.R.J. No relevant relationships. K.B. No relevant relationships. M.K.P. Multiple patents issued related to isotope production and application, as well as a patent pending for theranostics, no payments received to date. A.T.P. No relevant relationships. T.R.H. Research support to author’s institution from Ipsen and Advanced Accelerator Applications (a Novartis company); consulting fees from Ipsen and Advanced Accelerator Applications, paid to author’s institution; vice-president of the North American Neuroendocrine Tumor Society (NANETS), unpaid position; consultant to TerSera Therapeutics (personal payment). C.B.H. No relevant relationships. G.B.J. Grants or contracts from Pfizer, Novartis, MedTrace Pharma, Clarity Pharmaceuticals, Clovis Oncology, Viewpoint Molecular Targeting, and SOFIE, all paid to author’s institution; consulting fees from Pfizer, Novartis, Curium Pharma, Blue Earth Diagnostics, AstraZeneca, Siemens, and Morphimmune, paid to author’s institution; payment or honoraria from Prostate Cancer Research Institute (PCRI) for urology grand rounds; support from the Society of Nuclear Medicine and Molecular Imaging (SNMMI) for attending Gordon Research Conferences and Mayo CME courses; patents planned, issued, or pending for CRISMA PET, Alpha-PET theranostic platform, targeting meningiomas for PET imaging and therapy, cardiac PYP score; participation on a data safety monitoring board or advisory board for the SECuRE trial for Clarity Pharmaceuticals, the Targeted Imaging of Melanoma for Alpha-Particle Radiotherapy (TIMAR1) trial for Viewpoint Molecular Targeting, Pfizer, AstraZeneca, Novartis, and Siemens, all payments to author’s institution; chief scientific advisor for Nucleus RadioPharma. A.T.K. Primary investigator for Mayo Clinic Rochester for phase 3 VISION trial assessing LuPSMA therapy in patients with metastatic castration-resistant prostate cancer, sponsored by Novartis; consulting fees from Novartis for assessment of future LuPSMA therapy research; payment or honoraria for PSMA imaging presentation, an online education CME presentation sponsored by AXIS Medical Education.

Figures

Radionuclide therapy schematic. A radionuclide held in a chelator or cage or bound covalently is attached to a vector by a linker molecule. The vector binds to a molecular target to enable visualization of the target for diagnostic or treatment purposes and selective delivery of radiation therapy to the target. Alternatively, a free radionuclide ion can, in some circumstances, be used to target tumors or cancer cells, as with iodine 131, alastine 211, and radium 223. Created with BioRender.com.
 
Targeted α-particle therapy schematic. The radionuclide therapy is intravenously infused and binds to the tumor through a vector linked to the radionuclide. While bound to the tumor, α-particle emission occurs, selectively delivering radiation to the tumor. α Particles are more cytotoxic than β particles because they cause irreparable double-strand DNA breaks, resulting in cell death. Created with BioRender.com.
 
Targeted β-particle therapy schematic. While bound to the tumor, β-particle emission occurs, selectively delivering radiation to the tumor. β Particles exert therapeutic effects through reactive oxygen species, causing DNA damage via single-strand DNA breaks that may result in cell death if not repaired via DNA repair mechanisms. Created with BioRender.com.
 
Targeted α-particle and β-particle therapy comparison. Illustration shows the characteristic features of α and β particles. α Particles are positively charged particles composed of two protons and two neutrons, essentially the nucleus of a helium atom, and β particles are negatively charged particles, essentially electrons. α Particles have much greater mass, higher linear energy transfer (LET), travel a much shorter distance in tissue, and are more cytotoxic than β particles. The illustration includes specific values of these characteristics for reference but is not to scale. Created with BioRender.com.
 
Targeted α-particle therapy: radium 223 dichloride (223RaCl2) followed by actinium 225 (225Ac) prostate-specific membrane antigent (PSMA)–617. Images in a 66-year-old man with widely metastatic prostate cancer, with a Gleason score of 8 (4 + 4), that progressed following androgen deprivation, chemotherapy, and pelvic radiation. (A) Baseline gallium 68 (68Ga) PSMA-11 PET/CT image demonstrates intense PSMA uptake in numerous metastatic lesions (blue arrows indicate examples in the right scapula and both femurs). (B) 68Ga-PSMA-11 PET/CT image following three cycles of 223RaCl2 (a targeted α-particle therapy that incorporates within osteoblastic lesions but does not directly bind to cancer cells) shows progression of many osseous metastases (blue arrows), and the prostate-specific antigen (PSA) value increased. (C) Lutetium 177 (177Lu) PSMA-617 and 225Ac-PSMA-617 were both considered as treatment options. Following multidisciplinary discussion and shared decision-making with the patient, four cycles of 225Ac-PSMA-617 (a targeted α-particle therapy with affinity for PSMA) were administered 6 weeks apart, demonstrating dramatic response in the metastatic lesions, with near resolution of PSMA uptake at 68Ga-PSMA-11 PET/CT (blue arrows in the location of previous lesions) and a corresponding dramatic reduction in PSA.
 
Posttherapy monitoring of index lesions with SPECT/CT imaging. Fused SPECT/CT sagittal images in a 56-year-old man with prostate-specific membrane antigen (PSMA)–avid metastatic prostate cancer undergoing lutetium 177 (177Lu) PSMA-617 therapy. (A) Baseline fluorine 18 (18F) carboxy-fluoro-pyridine-carbonyl-amino-pentyl-ureido-pentanedioic acid (DCFPyL) PET/CT image demonstrates intense PSMA uptake in nodal, osseous, and hepatic metastases (arrows). (B–E) Posttherapy SPECT/CT image with 177Lu-PSMA-617 was performed approximately 24 hours after infusion of the therapeutic radiotracer after each of four cycles administered 6 weeks apart, demonstrating localization of the therapeutic radiopharmaceutical to the metastases. Index lesions in lymph node, bone, and liver (arrows) demonstrate decreased intensity of uptake with each cycle of therapy. (C) After cycle 2, the hepatic and nodal metastases were no longer conspicuous, and (E) after cycle 4, the spine metastasis was no longer conspicuous. Imaging the therapeutic radionuclide enables confirmation of effective delivery to the sites of cancer and detection of treatment response over the course of therapy, demonstrated by the changes in the imaged index lesions over time.

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Articles from Radiology: Imaging Cancer are provided here courtesy of Radiological Society of North America

borstkanker, theranostiek, prostaatkanker, schildklierkanker, prod. dr. Dalm, Erasmus MC


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