PT  - JOURNAL ARTICLE
AU  - John, Nikeith
AU  - Pathmanandavel, Sarennya
AU  - Crumbaker, Megan
AU  - Counter, William
AU  - Ho, Bao
AU  - Yam, Andrew O.
AU  - Wilson, Peter
AU  - Niman, Remy
AU  - Ayers, Maria
AU  - Poole, Aron
AU  - Hickey, Adam
AU  - Agrawal, Shikha
AU  - Perkins, Gary
AU  - Kallinen, Annukka
AU  - Eslick, Enid
AU  - Stockler, Martin R.
AU  - Joshua, Anthony M.
AU  - Nguyen, Andrew
AU  - Emmett, Louise
TI  - <sup>177</sup>Lu-PSMA SPECT Quantitation at 6 Weeks (Dose 2) Predicts Short Progression-Free Survival for Patients Undergoing <sup>177</sup>Lu-PSMA-I&T Therapy
AID  - 10.2967/jnumed.122.264677
DP  - 2023 Mar 01
TA  - Journal of Nuclear Medicine
PG  - 410--415
VI  - 64
IP  - 3
4099  - http://jnm.snmjournals.org/content/64/3/410.short
4100  - http://jnm.snmjournals.org/content/64/3/410.full
SO  - J Nucl Med2023 Mar 01; 64
AB  - 177Lu-PSMA is an effective treatment in metastatic castration-resistant prostate cancer (mCRPC). Our ability to assess response rates and adjust treatment may be improved using predictive tools. This study aimed to evaluate change in 177Lu-PSMA SPECT quantitative parameters to monitor treatment response. Methods: One hundred twenty-seven men with progressive mCRPC previously treated with androgen-signaling inhibition (99%) and chemotherapy (71%) received a median of 3 (interquartile range [IQR], 2–5) 8-GBq (IQR, 8–8.5 GBq) doses of 177Lu-PSMA-I&T. Imaging included 68Ga-PSMA-11 PET/CT (SUVmax > 15 at a single site and > 10 at all sites > 2 cm), diagnostic CT, and 177Lu SPECT/CT from vertex to mid thigh (24 h after treatment). 177Lu SPECT/CT quantitative analysis was undertaken at cycles 1 (baseline) and 2 (week 6) of treatment. Clinical and biochemical results were assessed to evaluate prostate-specific antigen (PSA) progression-free survival (PFS) and overall survival (OS). Results: A PSA reduction of more than 50% was seen in 58% (74/127). The median PSA PFS was 6.1 mo (95% CI, 5.5–6.7), and OS was 16.8 mo (95% CI, 13.5–20.1). At the time of analysis, 41% (52/127) were deceased. At baseline and week 6, 76% (96/127) had analyzable serial 177Lu SPECT/CT imaging. SPECT total tumor volume (TTV) was reduced between baseline and week 6 in 74% (71/96; median, −193; IQR, −486 to −41). Any increase in SPECT TTV between baseline and week 6 was associated with significantly shorter PSA PFS (hazard ratio, 2.5; 95% CI, 1.5–4.2; P = 0.0008) but not OS. Median PSA PFS in those with an increase in SPECT TTV was 3.7 mo (95% CI, 2.8–6.8), compared with 6.7 mo (95% CI, 5.8–10.6) in those with no increase in SPECT TTV. An increase in SPECT TTV greater than 20% was also associated with PSA PFS (hazard ratio, 1.9; 95% CI, 1.2–3.0; P = 0.008) but less significantly than any change in SPECT TTV. There was a significant difference in PSA PFS between patients with both increased PSA and SPECT TTV and patients with reduced SPECT TTV and PSA (median, 2.8 vs. 9.0 mo; P < 0.0001). Conclusion: Increasing PSMA SPECT TTV on quantitative 177Lu SPECT/CT predicts short progression-free survival and may play a future role as an imaging response biomarker, identifying when to cease or intensify 177Lu-PSMA therapy.