¹⁷⁷Lu-PSMA SPECT Quantitation at 6 Weeks (Dose 2) Predicts Short Progression-Free Survival for Patients Undergoing¹⁷⁷Lu-PSMA-I&T Therapy

Abstract

Lu-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 177 Lu-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 177 Lu-PSMA-I&T. Imaging included 68 Ga-PSMA-11 PET/CT (SUV max . 15 at a single site and . 10 at all sites . 2 cm), diagnostic CT, and 177 Lu 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 177 Lu SPECT/CT imaging. SPECT total tumor volume (TTV) was reduced between baseline and week 6 in 74% (71/96; median, 2193; IQR, 2486 to 241). 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 5 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 5 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 177 Lu SPECT/CT predicts short progression-free survival and may play a future role as an imaging response biomarker, identifying when to cease or intensify 177 Lu-PSMA therapy.

Patient outcomes following a response biomarker-guided approach to treatment using 177Lu-PSMA-I&T in men with metastatic castrate-resistant prostate cancer (Re-SPECT)

“…Change in week-6 177 Lu-SPECT tumour volume and rise in PSA at week 6 of 177 LuPSMA-I&T therapy have been previously shown to predict early PFS. 4 Utilising these biomarkers allowed 35% of men (in RG 1) to have a significant treatment break, a median 6 months, with retreatment at first subsequent PSA rise. These men had durable PFS and OS outcomes.…”

“…177 Lu-SPECT/CT was analysed semi-quantitatively by a nuclear medicine physician utilising MIM (LesionID™), MIM Software (Inc., Cleveland, OH, USA) software and a standardised semi-automated workflow to delineate regions of interest with a minimum SUV cut-off of 3 and lesion size ⩾ 0.2 mm. 4 All lesions identified quantitatively were manually reviewed and physiologic activity was removed. Whole body quantitation derived total tumour volume (TTV), SUVmax, and SUVmean for PSMA-SPECT at baseline and week 6.…”

Bone Metastases

“…177 Lu emits γ radiation at 113 keV (6.4% abundance) and 208 keV (11% abundance); 102 dosimetry is not typically performed, although posttherapy SPECT imaging is common and appears prognostic. 103 Other tumor-directed therapies like 131 I and 177 Lu-DOTATATE 15 treat bone and soft tissue metastases in their respective targets. Several potential therapies are in development, 104 including α-based therapies targeting PSMA 14 and somatostatin receptor and αor β-emitting conjugates with monoclonal antibodies targeting FGFR3 (overexpressed in bladder cancer and multiple myeloma), MC1R (melanoma), and FAP, 64 CD46, and CCK2 (multiple tumor types).…”

Improved quality control of [177Lu]Lu-PSMA I&T

“…This was complemented by the successful implementation of therapeutic application using the Lu-177 labelled PSMA ligands PSMA-617 (vipivotide tetraxetan) (Afshar-Oromieh et al 2015 ) and PSMA I&T (zadavotide guraxetan) (Weineisen et al 2015 ). [ 177 Lu]Lu-PSMA-617 has recently gained approval by the FDA (Pluvicto®), but also [ 177 Lu]Lu-PSMA I&T has proven high efficacy and safety in treating patients with advanced prostate cancer worldwide (Bu et al 2022 ; John et al 2022 ; Heck et al 2019 ; Hartrampf et al 2022 ), with very comparable outcomes (Schuchardt et al 2022 ; Hartrampf et al 2022 ). Today [ 177 Lu]Lu-PSMA I&T is widely used mainly because of its current better availability for local, in house preparation (Notni 2021 ).…”