The Tyr Phenomenon: A Hypocalcemic Response in High-Volume Treatment Responders to 177Lu-Prostate-Specific Membrane Antigen Therapy

Shejil Kumar; Megan Crumbaker; Christopher Harvey; Sarennya Pathmanandavel; Nikieth John; Mina M Swiha; Michelle M McDonald; Roderick Clifton-Bligh; Adrian Lee; Patricia Bastick; William Counter; Andrew Nguyen; Louise Emmett

doi:10.2967/jnumed.123.265759

The Tyr Phenomenon: A Hypocalcemic Response in High-Volume Treatment Responders to ¹⁷⁷Lu-Prostate-Specific Membrane Antigen Therapy

J Nucl Med. 2023 Sep;64(9):1412-1416. doi: 10.2967/jnumed.123.265759. Epub 2023 Jun 22.

Authors

Shejil Kumar¹, Megan Crumbaker², Christopher Harvey², Sarennya Pathmanandavel², Nikieth John^{2

3}, Mina M Swiha^{2

4}, Michelle M McDonald^{5

6}, Roderick Clifton-Bligh^{1

6}, Adrian Lee^{7

8

9}, Patricia Bastick¹⁰, William Counter², Andrew Nguyen^{2

3}, Louise Emmett^{11

3

5}

Affiliations

¹ Department of Endocrinology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
² Department of Theranostics and Nuclear Medicine, St. Vincent's Hospital, Sydney, New South Wales, Australia.
³ St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
⁴ Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
⁵ Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
⁶ School of Medical Science, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
⁷ Department of Medical Oncology, Royal North Shore Hospital, Sydney, New South Wales, Australia.
⁸ Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
⁹ Genesis Care, Sydney, New South Wales, Australia; and.
¹⁰ St. George Hospital, Sydney, New South Wales, Australia.
¹¹ Department of Theranostics and Nuclear Medicine, St. Vincent's Hospital, Sydney, New South Wales, Australia; louise.emmett@svha.org.au.

PMID: 37348918
DOI: 10.2967/jnumed.123.265759

Abstract

¹⁷⁷Lu-prostate-specific membrane antigen (PSMA) is an effective treatment for metastatic castration-resistant prostate cancer. Rarer treatment-related adverse events have not yet been described. Methods: We present case reviews of 2 men with a marked hypocalcemic osteosclerotic response to ¹⁷⁷Lu-PSMA-I&T therapy. A clinical dataset of ¹⁷⁷Lu-PSMA-I&T therapy was evaluated to estimate the incidence and clinical association with hypocalcemia. Results: Forty-one of the 127 men (32%) had a serum calcium drop, and 6 (5%) developed clinical hypocalcemia during ¹⁷⁷Lu-PSMA therapy. The baseline total tumor volume was significantly higher in those who developed hypocalcemia (median, 3,249 cm³ [interquartile range, 1,856-3,852] vs. 465 [interquartile range 135-1,172]; P = 0.002). The mean prostate-specific antigen response in those with hypocalcemia was 78% (SD, 24%). Conclusion: Hypocalcemia may occur in response to ¹⁷⁷Lu-PSMA-I&T, particularly with both high-volume bone metastases and a significant prostate-specific antigen response, and may be severe, requiring corticosteroids. Further evaluation of ¹⁷⁷Lu-PSMA-induced hypocalcemia is required to better understand mechanisms, optimal treatments, and repercussions from any subsequent osteosclerotic response.

Keywords: 177Lu-PSMA; hypocalcemia; metastatic prostate cancer.

MeSH terms

Dipeptides / therapeutic use
Heterocyclic Compounds, 1-Ring / therapeutic use
Humans
Hypocalcemia* / chemically induced
Hypocalcemia* / drug therapy
Lutetium / therapeutic use
Male
Prostate / pathology
Prostate-Specific Antigen
Prostatic Neoplasms, Castration-Resistant* / drug therapy
Prostatic Neoplasms, Castration-Resistant* / radiotherapy
Treatment Outcome

Substances

Prostate-Specific Antigen
Dipeptides
Heterocyclic Compounds, 1-Ring
Lutetium