Lutetium-177 (177Lu) prostate-specific membrane antigen (177Lu-PSMA) is a radiolabelled
small-molecule inhibitor that binds with high affinity to PSMA and delivers β particle
radiation. [177Lu]Lu-PSMA-617 (Pluvicto) was approved by the U.S. Food and Drug
administration (FDA) in patients with late-stage, PSMA positive metastatic
castration-resistant prostate cancer (mCRPC) based on the results from the phase 3 VISION
trial [1].
Early identification of tumor progression may reduce unnecessary therapy cycles and their
associated risk of adverse events as well as reducing costs and improving patient care by
initiating an earlier change in treatment towards a possibly more efficacious therapy.
Response Evaluation Criteria In PSMA-imaging (RECIP) version 1.0 is an evidence-based
framework to evaluate therapeutic efficacy in metastatic prostate cancer using
PSMA-imaging[2,3]. Interim PSMA-PET/CT by RECIP 1.0 criteria performed at 10 weeks after
two cycles of PSMA theranostics ([177Lu]Lu-PSMA- 617 or [177Lu]Lu-PSMA-I&T) is prognostic
for overall survival[2]. RECIP 1.0 criteria were validated based on overall survival
outcome for measuring response in metastatic prostate cancer during androgen
receptor-signaling inhibitors[4], as well as in early-stage prostate cancer in patients
with biochemical recurrence after initial therapy[5].
Lutetium-177 is a beta therapy that also emits 11% gamma rays, which can be utilised to
derive whole-body tomographic images similar to PSMA-PET/CT. Serial Lutetium-177
PSMA-targeted single photon emission tomography/computed tomography
[177Lu]Lu-PSMA-SPECT/CT henceforth referred to as LuPSMASPECT/ CT has potential as an
imaging response biomarker for 177Lu-PSMA therapy. This principle enables image
quantitation and evaluation after every treatment dose. SPECT/CT post [177Lu]Lu-PSMA
administration represents a potentially cost-effective alternative to interim
PSMA-PET/CT.
Preliminary results have shown a good correlation between changes in LuPSMASPECT/ CT
during PSMA theranostics and clinical outcome. LuPSMA-SPECT/CT can provide effective
response information as early as 6 weeks after initiation of [177Lu]Lu-PSMA-I&T, i.e. any
increase in total tumor volume on SPECT/CT imaging was associated with shorter PSA-PFS
(median: 3.7 vs 6.7 months; HR, 2.5; 95% CI 1.5-4.2; p<0.001)[6]. Changes in total tumor
volume on 12-week LuPSMASPECT/ CT were also found to be correlated with progression-free
survival after [177Lu]Lu-PSMA-I&T[7].
The growing evidence suggesting that LuPSMA-SPECT/CT is a new, early surrogate marker for
assessing response to treatment has several potential upsides, including the potential
replacement of interim PSMA-PET/CT, therefore costsaving, radiation exposure-saving, and
SPECT/CT imaging being more convenient and widely available.
Given that data regarding SPECT/CT-based treatment response monitoring during PSMA
theranostics are limited, this study aims to prospectively investigate the role of
LuPSMA-SPECT/CT imaging for response evaluation during treatment with [177Lu]Lu-PSMA in
mCRPC patients.