Principal Investigator

Prof. Dr. nat. phil. Katharina Lückerath

Clinic for Nuclear Medicine                                                                                        
University Hospital Essen

Prof. Dr. Katharina Lückerath

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Summary

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Late diagnosis and extreme refractoriness to chemo- and targeted-therapies are major reasons for the dismal prognosis. New, effective therapeutic options are urgently needed. In the current project we will explore a new radioimmunotheranostic as a new concept in PDAC treatment. The term theranostics combines the words diagnosis and therapy; it represents a precision medicine approach relying on a radioligand for non-invasive, imaging-based diagnosis that helps to select patients for therapy with the therapeutic version of the same radioligand (radioimmunotherapy). We will determine the potential of our radioimmunotherapy to exert anti-PDAC efficacy by enhancing its immunogenicity.
 

Klose JM, Wosniack J, Iking J, Staniszewska M, Zarrad F, Trajkovic-Arsic M, Herrmann K, Fragoso Costa P, Lueckerath K, Fendler WP. Administration routes for SSTR- / PSMA- and FAP-directed theranostic radioligands in mice. J Nucl Med. 2022 Jan 6;. doi: 10.2967/jnumed.121.263453. [Epub ahead of print] PubMed PMID: 34992151. 

Ferdinandus J, Fendler WP, Lueckerath K, Berliner C, Kurzidem S, Hadaschik E, Klode J, Zimmer L, Livingstone E, Schadendorf D, Herrmann K, Becker JC, Ugurel S. Response to combined peptide receptor radionuclide therapy and checkpoint immunotherapy with ipilimumab plus nivolumab in metastatic Merkel cell carcinoma. J Nucl Med. 2021 Sep 2;. doi: 10.2967/jnumed.121.262344. [Epub ahead of print] PubMed PMID: 34475234. 

Veach DR, Storey CM, Lückerath K, Braun K, von Bodman C, Lamminmäki U, Kalidindi T, Strand SE, Strand J, Altai M, Damoiseaux R, Zanzonico P, Benabdallah N, Pankov D, Scher HI, Scardino P, Larson SM, Lilja H, McDevitt MR, Thorek DLJ, Ulmert D. PSA-Targeted Alpha-, Beta-, and Positron-Emitting Immunotheranostics in Murine Prostate Cancer Models and Nonhuman Primates. Clin Cancer Res. 2021 Apr 1;27(7):2050-2060. doi: 10.1158/1078-0432.CCR-20-3614. Epub 2021 Jan 13. PubMed PMID: 33441295. 

Czernin J, Current K, Mona CE, Nyiranshuti L, Hikmat F, Radu CG, Lückerath K. Immune-Checkpoint Blockade Enhances ²²⁵Ac-PSMA617 Efficacy in a Mouse Model of Prostate Cancer. J Nucl Med. 2021 Feb;62(2):228-231. doi: 10.2967/jnumed.120.246041. Epub 2020 Jul 9. PubMed PMID: 32646877. 

Stuparu AD, Capri JR, Meyer C, Le TM, Evans-Axelsson SL, Current K, Lennox M, Mona CE, Fendler WP, Calais J, Eiber M, Dahlbom M, Czernin J, Radu CG, Lückerath K*, Slavik R*. Mechanisms of Resistance to Prostate-Specific Membrane Antigen-Targeted Radioligand Therapy in a Mouse Model of Prostate Cancer. J Nucl Med. 2020 Dec 4;. doi: 10.2967/jnumed.120.256263. [Epub ahead of print] PubMed PMID: 33277393. *shared last author

Bicak M, Lückerath K, Kalidindi T, Phelps ME, Strand SE, Morris MJ, Radu CG, Damoiseaux R, Peltola MT, Peekhaus N, Ho A, Veach D, Malmborg Hager AC, Larson SM, Lilja H, McDevitt MR, Klein RJ, Ulmert D. Genetic signature of prostate cancer mouse models resistant to optimized hK2 targeted α-particle therapy. Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):15172-15181. doi: 10.1073/pnas.1918744117. Epub 2020 Jun 12. PubMed PMID: 32532924; PubMed Central PMCID: PMC7334567. 

Current K, Meyer C, Magyar CE, Mona CE, Almajano J, Slavik R, Stuparu AD, Cheng C, Dawson DW, Radu CG, Czernin J, Lueckerath K. Investigating PSMA-Targeted Radioligand Therapy Efficacy as a Function of Cellular PSMA Levels and Intratumoral PSMA Heterogeneity. Clin Cancer Res. 2020 Jun 15;26(12):2946-2955. doi: 10.1158/1078-0432.CCR-19-1485. Epub 2020 Jan 13. PubMed PMID: 31932492; PubMed Central PMCID: PMC7299755. 

Stuparu AD, Meyer CAL, Evans-Axelsson SL, Lückerath K, Wei LH, Kim W, Poddar S, Mona CE, Dahlbom M, Girgis MD, Radu CG, Czernin J, Slavik R. Targeted alpha therapy in a systemic mouse model of prostate cancer - a feasibility study. Theranostics. 2020;10(6):2612-2620. doi: 10.7150/thno.42228. eCollection 2020. PubMed PMID: 32194823; PubMed Central PMCID: PMC7052903. 

Lückerath K, Wei L, Fendler WP, Evans-Axelsson S, Stuparu AD, Slavik R, Mona CE, Calais J, Rettig M, Reiter RE, Herrmann K, Radu CG, Czernin J, Eiber M. Preclinical evaluation of PSMA expression in response to androgen receptor blockade for theranostics in prostate cancer. EJNMMI Res.2018 Oct 29;8(1):96. doi: 10.1186/s13550-018-0451-z. PubMed PMID: 30374743; PubMed Central PMCID: PMC6206308. 

Lückerath K, Stuparu AD, Wei L, Kim W, Radu CG, Mona CE, Calais J, Rettig M, Reiter RE, Czernin J, Slavik R, Herrmann K, Eiber M, Fendler WP. Detection Threshold and Reproducibility of ⁶⁸Ga-PSMA11 PET/CT in a Mouse Model of Prostate Cancer. J Nucl Med. 2018 Sep;59(9):1392-1397. doi: 10.2967/jnumed.118.207704. Epub 2018 Mar 30. PubMed PMID: 29602819; PubMed Central PMCID: PMC6910618. 

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