18 mei 2020: als update van onderstaande studie is de volgende studie interessant: 

https://kidneycan.org/wp-content/uploads/2019/12/03-Development-and-Potentials-for-ImmunoPET-Imaging-David-Leung.pdf

In de PDF worden verschillende manieren aangegeven om bepaalde tumorexpressie en DNA mutaties geschikt voor toepassen van immuuntherapie bij verschillende vormen van kanker op een rijtje gezet. 

13 maart 2018: Bron: The Journal of Nuclear Medicin

Bristol-Myers Squibb, de producent van o.a. nivolumab, heeft een weinig belastende manier gevonden om vast te stellen of een kankerpatiënt voldoende P1-L1 expressie heeft om de kans op het aanslaan van immuuntherapie met een anti-PD medicijn te doen slagen. 

Aan een petscan wordt een stofje, Novel 18F-Labeled Adnectin geheten, toegevoegd die de PD-L1 expressie laat oplichten op het oppervlak van de tumorcellen. Het is nog maar een muizenstudie maar ik begrijp uit het persbericht (zie odneraan artikel) dat in ieder geval Bristol-Meyers Squibb deze manier van meten snel gaat gebruiken.

Klik op de titel van de studie voor het volledige studierapport (persbericht staat onderaan dit artikel: Synthesis and Biologic Evaluation of a Novel 18F-Labeled Adnectin as a PET Radioligand for Imaging PD-L1 Expression

View larger version:

FIGURE 6.

Representative whole-body PET (maximal-intensity projection) images 90 min after injection of (A) 18F-BMS-986192 only and (B) 18F-BMS-986192 with a coadministration of 1 mg/kg BMS-986192 in the same monkey. (C) Representative anti–PD-L1 immunohistochemistry of healthy monkey spleen tissue.

CONCLUSION

A novel 18F-labeled adnectin radioligand was developed for PET imaging of PD-L1–expressing tissues. In addition, an improved methodology was described based on a unique prosthetic group that allows for the 18F labeling of adnectins under mild conditions. Using copper-free click chemistry, we generated 18F-BMS-986192 with picomolar affinity toward the human PD-L1 receptor in high radiochemical purity and high specific activity. This methodology addresses important issues associated with the 18F labeling of proteins and should be applicable to related systems. In vivo imaging demonstrated rapid delivery of 18F-BMS-986192 to PD-L1–expressing tumors and rapid clearance from non-PD-L1–expressing tumors and tissues. 18F-BMS-986192 was highly stable in vivo and had low background signals in organs of interest such as the lung. The results of this study demonstrate the feasibility of preparing 18F anti–PD-L1 adnectins for the measurement of PD-L1 expression in tumors. Radiation dosimetry estimates indicate that this tracer is safe to administer in human studies. Clinical studies with 18F-BMS-986192 are currently under way to better understand this checkpoint pathway and PD-L1 expression in human tumors.

Hier het persbericht over deze studie:

Researchers develop new approach that uses single PET scan to personalize cancer treatment

RESTON, Va. - Researchers have developed a same-day, noninvasive positron emission tomography (PET)-based imaging approach to assess PD-L1 positive tumors, and the study is presented in the featured article of The Journal of Nuclear Medicine's March issue.

A healthy immune system strikes a delicate balance between eradicating infections and cancers and not overreacting to damage one's own tissue. Immune checkpoints help control the immune response, but tumors exploit these checkpoint pathways by expressing special proteins that evade antitumor immune responses. One major checkpoint inhibitor pathway is the PD-1 pathway, and its ligand is PD-L1.

In this study, the PD-L1 ligand, which enables cancer to evade a person's immune system, has been successfully targeted for the first time with a fluorine-18 (18F)-labeled PD-L1 radioligand. Until now, efforts to predict response to treatments targeting PD-1 or PD-L1 have typically been limited to evaluation of a single patient biopsy sample.

"This approach represents an opportunity for physicians to noninvasively assess all of a patient's tumors for PD-L1 expression with a single PET scan and timely readout," explains David J. Donnelly, PhD, at Bristol-Myers Squibb Research and Development in Princeton, New Jersey. "This may help guide treatment decisions and assess treatment response, to help identify the right treatment for the right patient at the right time and right dose."

For the study, an anti-PD-L1 adnectin (an engineered, target-binding protein) was labeled with 18F to generate 18F-BMS-986192, which was then evaluated in mice bearing bilateral PD-L1(-) and PD-L1(+) subcutaneous tumors. 18F-BMS-986192 was also evaluated for distribution, binding and radiation dosimetry in healthy cynomolgus monkey. The results of the study demonstrate the feasibility of the approach, and the radiation dosimetry estimates indicate that the tracer is safe to administer in human studies. Clinical studies are now underway to measure PD-L1 expression in human tumors.

###

Authors of "Synthesis and Biological Evaluation of a Novel 18F-labeled Adnectin as a PET Radioligand for Imaging PD-L1 Expression" include David J. Donnelly, R. Adam Smith, Paul Morin, Daša Lipovšek, Jochem Gokemeijer, Daniel Cohen, Virginie Lafont, Tritin Tran, Erin L. Cole, Martin Wright, Joonyoung Kim, Adrienne Pena, Daniel Kukral, Douglas D. Dischino, Patrick Chow, Jinping Gan, Olufemi Adelakun, Xi-Tao Wang, Kai Cao, David Leung, Samuel J. Bonacorsi, Jr., and Wendy Hayes, Bristol-Myers Squibb Research and Development, Princeton, New Jersey.

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  • Published online Oct. 12, 2017.

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REFERENCES

  1. 1.↵
    1. Pardoll DM
    . The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–264.
    CrossRefMedlineGoogle Scholar
  2. 2.↵
    1. Riella LV,
    2. Paterson AM,
    3. Sharpe AH,
    4. Chandraker A
    . Role of the PD-1 pathway in the immune response. Am J Transplant. 2012;12:2575–2587.
    CrossRefMedlineGoogle Scholar
  3. 3.↵
    1. Keir ME,
    2. Butte MJ,
    3. Freeman GJ,
    4. Sharpe AH
    . PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.
    CrossRefMedlineGoogle Scholar
  4. 4.↵
    1. Herbst RS,
    2. Soria JC,
    3. Kowanetz M,
    4. et al
    . Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–567.
    CrossRefMedlineGoogle Scholar
  5. 5.↵
    1. Freeman GJ,
    2. Long AJ,
    3. Iwai Y,
    4. et al
    . Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192:1027–1034.
    Abstract/FREE Full Text
  6. 6.↵
    1. Kazandjian D,
    2. Suzman DL,
    3. Blumenthal G,
    4. et al
    . FDA approval summary: Nivolumab for the treatment of metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy. Oncologist. 2016;21:634–642.
    Abstract/FREE Full Text
  7. 7.
    1. Gyawali B,
    2. Ota A,
    3. Ando Y
    . Nivolumab in nonsquamous non-small-cell lung cancer. N Engl J Med. 2016;374:493.
    Google Scholar
  8. 8.
    1. Borghaei H,
    2. Brahmer J
    . Nivolumab in nonsquamous non-small-cell lung cancer. N Engl J Med. 2016;374:493–494.
    Google Scholar
  9. 9.
    1. Herbst RS,
    2. Baas P,
    3. Kim DW,
    4. et al
    . Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387:1540–1550.
    CrossRefMedlineGoogle Scholar
  10. 10.↵
    1. Weinstock M,
    2. McDermott D
    . Targeting PD-1/PD-L1 in the treatment of metastatic renal cell carcinoma. Ther Adv Urol. 2015;7:365–377.
    CrossRefMedlineGoogle Scholar
  11. 11.↵
    1. He J,
    2. Hu Y,
    3. Hu M,
    4. Li B
    . Development of PD-1/PD-L1 pathway in tumor immune microenvironment and treatment for non-small cell lung cancer. Sci Rep. 2015;5:13110.
    CrossRefMedlineGoogle Scholar
  12. 12.↵
    1. Chakravarti N,
    2. Prieto VG
    . Predictive factors of activity of anti-programmed death-1/programmed death ligand-1 drugs: immunohistochemistry analysis. Transl Lung Cancer Res. 2015;4:743–751.
    MedlineGoogle Scholar
  13. 13.↵
    1. Topalian SL,
    2. Taube JM,
    3. Anders RA,
    4. Pardoll DM
    . Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer. 2016;16:275–287.
    CrossRefMedlineGoogle Scholar
  14. 14.↵
    1. Patel SP,
    2. Kurzrock R
    . PD-L1 Expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14:847–856.
    Abstract/FREE Full Text
  15. 15.↵
    1. Ilie M,
    2. Long-Mira E,
    3. Lassalle S,
    4. et al
    . Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies. Ann Oncol. 2016;27:147–153.
    CrossRefMedlineGoogle Scholar
  16. 16.↵
    1. Chatterjee S,
    2. Lesniak WG,
    3. Gabrielson M,
    4. et al
    . A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors. Oncotarget. 2016;7:10215–10227.
    MedlineGoogle Scholar
  17. 17.
    1. Wu AM
    . Antibodies and antimatter: the resurgence of immuno-PET. J Nucl Med. 2009;50:2–5.
    Abstract/FREE Full Text
  18. 18.
    1. Wu AM
    . Engineering multivalent antibody fragments for in vivo targeting. In: Lo BKC, ed. Antibody Engineering: Methods and Protocols. Totowa, NJ: Humana Press; 2004:209–225.
    Google Scholar
  19. 19.↵
    1. Hettich M,
    2. Braun F,
    3. Bartholoma MD,
    4. Schirmbeck R,
    5. Niedermann G
    . High-resolution PET imaging with therapeutic antibody-based PD-1/PD-L1 checkpoint tracers. Theranostics. 2016;6:1629–1640.
    CrossRefMedlineGoogle Scholar
  20. 20.↵
    1. Lesniak WG,
    2. Chatterjee S,
    3. Gabrielson M,
    4. et al
    . PD-L1 detection in tumors using 64Cu-atezolizumab with PET. Bioconjug Chem. 2016;27:2103–2110.
    Google Scholar
  21. 21.↵
    1. Heskamp S,
    2. Hobo W,
    3. Molkenboer-Kuenen JD,
    4. et al
    . Noninvasive imaging of tumor PD-L1 expression using radiolabeled anti-PD-L1 antibodies. Cancer Res. 2015;75:2928–2936.
    Abstract/FREE Full Text
  22. 22.↵
    1. Olafsen T,
    2. Sirk SJ,
    3. Olma S,
    4. Shen CKF,
    5. Wu AM
    . ImmunoPET using engineered antibody fragments: fluorine-18 labeled diabodies for same-day imaging. Tumour Biol. 2012;33:669–677.
    CrossRefMedlineGoogle Scholar
  23. 23.↵
    1. Lipovšek D
    . Adnectins: engineered target-binding protein therapeutics. Protein Eng Des Sel. 2011;24:3–9.
    CrossRefMedlineGoogle Scholar
  24. 24.↵
    1. Koide A,
    2. Koide S
    . Monobodies: antibody mimics based on the scaffold of the fibronectin type III domain. Methods Mol Biol. 2007;352:95–109.
    MedlineGoogle Scholar
  25. 25.↵
    1. Maute RL,
    2. Gordon SR,
    3. Mayer AT,
    4. et al
    . Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging. Proc Natl Acad Sci USA. 2015;112:E6506–E6514.
    Abstract/FREE Full Text
  26. 26.↵
    1. Chatterjee S,
    2. Lesniak WG,
    3. Miller MS,
    4. et al
    . Rapid PD-L1 detection in tumors with PET using a highly specific peptide. Biochem Biophys Res Commun. 2017;483:258–263.
    Google Scholar
  27. 27.
    1. Rossin R,
    2. Berndorff D,
    3. Friebe M,
    4. Dinkelborg LM,
    5. Welch MJ
    . Small-animal PET of tumor angiogenesis using a 76Br-labeled human recombinant antibody fragment to the ED-B domain of fibronectin. J Nucl Med. 2007;48:1172–1179.
    Abstract/FREE Full Text
  28. 28.↵
    1. Hackel BJ,
    2. Kimura RH,
    3. Gambhir SS
    . Use of 64Cu-labeled fibronectin domain with EGFR-overexpressing tumor xenograft: molecular imaging. Radiology. 2012;263:179–188.
    CrossRefMedlineGoogle Scholar
  29. 29.↵
    1. Natarajan A,
    2. Hackel BJ,
    3. Gambhir SS
    . A novel engineered anti-CD20 tracer enables early time PET imaging in a humanized transgenic mouse model of B-cell non-Hodgkins lymphoma. Clin Cancer Res. 2013;19:6820–6829.
    Abstract/FREE Full Text
  30. 30.↵
    1. Weissleder R,
    2. Ross BD,
    3. Rehemtulla A,
    4. Gambhir SS
    . Molecular Imaging, Principles and Practices. Vol. 13. Shelton, CT: Peoples Medical Publishing House–USA; 2011.
    Google Scholar
  31. 31.↵
    1. Gill HS,
    2. Marik J
    . Preparation of 18F-labeled peptides using the copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition. Nat Protoc. 2011;6:1718–1725.
    MedlineGoogle Scholar
  32. 32.↵
    1. Akizawa H,
    2. Uehara T,
    3. Arano Y
    . Renal uptake and metabolism of radiopharmaceuticals derived from peptides and proteins. Adv Drug Deliv Rev. 2008;60:1319–1328.
    CrossRefMedlineGoogle Scholar
  • Received for publication July 31, 2017.
  • Accepted for publication September 19, 2017.

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immuuntherapie, anti-PD medicijnen, dendritische celtherapie, checkpoint remmers, klinisch kankervrij, fase III studies, geregistreerde medicijnen, Novel 18F-Labeled Adnectin


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