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Research ArticleClinical Investigation

First Clinical Results for PSMA-Targeted α-Therapy Using 225Ac-PSMA-I&T in Advanced-mCRPC Patients

Mathias Johannes Zacherl, Franz Josef Gildehaus, Lena Mittlmeier, Guido Böning, Astrid Gosewisch, Vera Wenter, Marcus Unterrainer, Nina Schmidt-Hegemann, Claus Belka, Alexander Kretschmer, Jozefina Casuscelli, Christian G. Stief, Marcus Unterrainer, Peter Bartenstein, Andrei Todica and Harun Ilhan
Journal of Nuclear Medicine May 2021, 62 (5) 669-674; DOI: https://doi.org/10.2967/jnumed.120.251017
Mathias Johannes Zacherl
1Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
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Franz Josef Gildehaus
1Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
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Lena Mittlmeier
1Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
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Guido Böning
1Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
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Astrid Gosewisch
1Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
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Vera Wenter
1Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
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Marcus Unterrainer
1Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
2Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
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Nina Schmidt-Hegemann
2Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
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Claus Belka
2Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
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Alexander Kretschmer
3Department of Urology, University Hospital, LMU Munich, Munich, Germany; and
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Jozefina Casuscelli
3Department of Urology, University Hospital, LMU Munich, Munich, Germany; and
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Christian G. Stief
3Department of Urology, University Hospital, LMU Munich, Munich, Germany; and
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Marcus Unterrainer
1Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
4Department of Radiology, University Hospital, LMU Munich, Munich, Germany
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Peter Bartenstein
1Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
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Andrei Todica
1Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
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Harun Ilhan
1Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany
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  • FIGURE 1.
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    FIGURE 1.

    Waterfall plots of PSA, lactate dehydrogenase (LDH), and ALP response after TAT using 225Ac-PSMA-I&T. A and B describe PSA changes after 8 wk and best PSA response after first TAT cycle. C and D describe best LDH and ALP response after median of 2 TAT cycles.

  • FIGURE 2.
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    FIGURE 2.

    A 79-y-old mCRPC patient (patient 11) with lymphatic and bone metastases. Patient received 2 cycles of 177Lu-PSMA RLT (cumulative activity, 10.5 GBq) after failure of docetaxel and showed initial response. However, disease progression was observed in January 2019 after 2 additional 177Lu-PSMA RLT cycles (cumulative activity, 12 GBq), and patient was admitted for 225Ac-PSMA-I&T TAT. PSA follow-up and PSMA PET showed impressive response after 2 cycles (cumulative activity, 13.4 MBq). Unfortunately, patient developed grade 3 leukocytopenia, and TAT could not be continued. Disease progression was observed in November 2019 after best supportive care (BSC).

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    TABLE 1

    Patient Characteristics

    CharacteristicValue
    Patients14 (100%)
    Age (y)
     Median75 (64–80)
     ≥758 (57%)
    ECOG performance score
     ≤111 (79%)
     23 (21%)
    PSA at start of 225Ac-PSMA-I&T (ng/mL)112 (20.5–818)
    Hemoglobin at start of 225Ac-PSMA-I&T (g/dL)10.3 (5.6–12.5)
    Platelets at start of 225Ac-PSMA-I&T (g/L)246 (72–412)
    ALP at start of 225Ac-PSMA-I&T (U/L) (reference range, 40−130)143 (67–695)
    Site of metastases before 225Ac-PSMA-I&T
     Bone (any)13 (93%)
     Bone (superscan pattern)5 (36%)
     Lymph node10 (71%)
     Visceral metastasis3 (21%)
     Liver1 (7%)
     Lung3 (21%)
     Other organs1 (7%)
    Therapy before start of 225Ac-PSMA-I&T
    Prostatectomy9 (64%)
    Radiation therapy12 (86%)
    Prostate or locoregional lymph nodes10 (71%)
    Distant (nonregional lymph nodes, bone)6 (43%)
    Androgen deprivation therapy14 (100%)
    Abiraterone OR enzalutamide11 (79%)
    Abiraterone AND enzalutamide4 (29%)
    Docetaxel11 (79%)
    Docetaxel AND cabazitaxel1 (7%)
    177Lu-PSMA RLT11 (79%)
    223Ra-dichloride2 (14%)
    • ECOG = eastern cooperative oncology group.

    • Qualitative data are number and percentage; continuous data are median and range.

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    TABLE 2

    Therapy-Related Hematologic and Renal Adverse Events After 225Ac-PSMA-I&T According to Common Terminology Criteria for Adverse Events, Version 5.0

    EventBefore TAT After TAT
    Gr. 1Gr. 2Gr. 3Gr. 4Gr. 1Gr. 2Gr. 3Gr. 4
    Hematologic
     Anemia8 (57%)4 (29%)2 (14%)3 (21%)8 (57%)3 (21%)—
     Thrombopenia3 (21%)1 (7%)——3 (21%)3 (21%)——
     Leukopenia2 (14%)1 (7%)——4 (28%)—1 (7%)—
    Renal1 (7%)———1 (7%)1 (7%)——
    Gastrointestinal
     Xerostomia6 (43%)2 (14%)—ND8 (57%)5 (36%)—ND
     Dysgeusia————5 (36%)1 (7%)——
     Anorexia9 (64%)———7 (50%)2 (14%)——
     Nausea————4 (29%)1 (7%)——
    General
     Fatigue10 (71%)1 (7%)——6 (43%)6 (43%)——
     Weight lossNANANANA4 (29%)———
    • Gr. = grade; ND = not defined; NA = not applicable.

    • Data are number and percentage.

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    TABLE 3

    Laboratory Parameters at Baseline and After 225Ac-PSMA TAT

    ParameterBefore 225Ac-PSMA-I&T TATAfter 225Ac-PSMA-I&T TAT
    Hemoglobin (g/dL)10.11 ± 1.949.15 ± 1.52
    Platelets (g/L)225.29 ± 99.11190.00 ± 104.28
    Leukocytes (g/L)5.59 ± 1.924.89 ± 1.78
    Sodium (mmol/L)138.00 ± 2.66137.69 ± 4.31
    Potassium (mmol/L)4.39 ± 0.654.15 ± 0.32
    Calcium (mmol/L)2.20 ± 0.082.27 ± 0.09
    Creatinine (mg/dL)0.96 ± 0.180.95 ± 0.37
    eGFR (mL/min)82.57 ± 17.4279.57 ± 18.72
    BUN (mg/dL)41.36 ± 14.6835.69 ± 10.85
    ALT (U/L)16.77 ± 6.9220.14 ± 11.35
    AST (U/L)41.36 ± 31.5649.69 ± 33.96
    Albumin (g/dL)4.05 ± 0.453.80 ± 0.66
    Bilirubin (mg/dL)0.35 ± 0.200.49 ± 0.35
    ALP (U/L)237.21 ± 188.85409.64 ± 312.49
    LDH (U/L)505.14 ± 416.90618.62 ± 551.64
    • eGFR = estimated glomerular filtration rate; BUN = blood urea nitrogen; ALT = alanine aminotransferase; AST = aspartate aminotransferase; LDH = lactate dehydrogenase.

    • Data are mean ± SD.

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Journal of Nuclear Medicine: 62 (5)
Journal of Nuclear Medicine
Vol. 62, Issue 5
May 10, 2021
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First Clinical Results for PSMA-Targeted α-Therapy Using 225Ac-PSMA-I&T in Advanced-mCRPC Patients
Mathias Johannes Zacherl, Franz Josef Gildehaus, Lena Mittlmeier, Guido Böning, Astrid Gosewisch, Vera Wenter, Marcus Unterrainer, Nina Schmidt-Hegemann, Claus Belka, Alexander Kretschmer, Jozefina Casuscelli, Christian G. Stief, Marcus Unterrainer, Peter Bartenstein, Andrei Todica, Harun Ilhan
Journal of Nuclear Medicine May 2021, 62 (5) 669-674; DOI: 10.2967/jnumed.120.251017

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First Clinical Results for PSMA-Targeted α-Therapy Using 225Ac-PSMA-I&T in Advanced-mCRPC Patients
Mathias Johannes Zacherl, Franz Josef Gildehaus, Lena Mittlmeier, Guido Böning, Astrid Gosewisch, Vera Wenter, Marcus Unterrainer, Nina Schmidt-Hegemann, Claus Belka, Alexander Kretschmer, Jozefina Casuscelli, Christian G. Stief, Marcus Unterrainer, Peter Bartenstein, Andrei Todica, Harun Ilhan
Journal of Nuclear Medicine May 2021, 62 (5) 669-674; DOI: 10.2967/jnumed.120.251017
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Keywords

  • metastatic castration-resistant prostate cancer
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  • targeted α-therapy
  • 225Ac and 177Lu
  • PSMA
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