RT Journal Article SR Electronic T1 The Tyr Phenomenon: A Hypocalcemic Response in High-Volume Treatment Responders to 177Lu-Prostate-Specific Membrane Antigen Therapy JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1412 OP 1416 DO 10.2967/jnumed.123.265759 VO 64 IS 9 A1 Kumar, Shejil A1 Crumbaker, Megan A1 Harvey, Christopher A1 Pathmanandavel, Sarennya A1 John, Nikieth A1 Swiha, Mina M. A1 McDonald, Michelle M. A1 Clifton-Bligh, Roderick A1 Lee, Adrian A1 Bastick, Patricia A1 Counter, William A1 Nguyen, Andrew A1 Emmett, Louise YR 2023 UL http://jnm.snmjournals.org/content/64/9/1412.abstract AB 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.