Page 52 - ARNM-3-3

Advances in Radiotherapy
& Nuclear Medicine LuPSMA response patterns on PSMA PET

median PSA progression-free survival (PSA-PFS) was 8.6 months; median OS was
22.0 months. At post-treatment imaging, 54% (20/37) showed progression. TLW
classified 24% as “responders,” 41% as “low-volume progressors,” and 35% as “high-
volume progressors.” “Responders” had longer OS than “low-volume progressors”
(median 17.7 vs. 12.0 months) or “high-volume progressors” (median 7.5 months,
p=0.005). RECIP 1.0 classified 24% as partial response, 51% stable disease, and 24%
as progressive disease. In summary, TLW shows potential to delineate complex
response patterns. Following validation in larger cohorts, TLW will inform therapeutic
decision-making.

Keywords: Metastatic prostate cancer; Theranostics; Lutetium-prostate-specific
membrane antigen; Therapeutic response

1. Introduction protocol received approval from the St Vincent’s Hospital
Institutional Review Board (IRB; HREC/17/SVH/19;
Lutetium-177 prostate-specific membrane ACTRN12618001073291), and all participants provided
antigen-617 ( Lu-PSMA-617) is an active treatment written, informed consent.
177
for advanced prostate cancer. In landmark clinical
1,2
trials, pre-treatment gallium-68-labeled prostate- 2.1. Screening
specific membrane antigen-11 ( Ga-PSMA-11) positron Men with progressive mCRPC, based on conventional
68
emission tomography/computed tomography (PET/CT) imaging or a rising prostate-specific antigen (PSA)
and fluorine-18-fluorodeoxyglucose (FDG) PET have according to Prostate Cancer Working Group 3 (PCWG3)
facilitated the selection of patients most likely to benefit criteria, were eligible. Prior treatment with docetaxel
9
from Lu-PSMA-617 therapy. However, the use of PET and/or cabazitaxel and an ASI (abiraterone and/or
177
1-3
imaging for monitoring therapeutic response and detecting enzalutamide) was required. Imaging eligibility required
treatment failure patterns is less well understood. Interim a SUV >15 on PSMA PET at ≥1 site, an SUV >10 at
4,5
and post-treatment prostate-specific membrane antigen all measurable sites, and no FDG-positive, PSMA-negative
max
max
(PSMA) PET imaging provide a unique opportunity sites of disease.
to measure dynamic changes in PSMA expression and
tumor volume, enabling a more informative assessment of 2.2. Study treatment
response than conventional imaging (CT and whole-body
bone scintigraphy). Each treatment cycle included administration of 7.5 GBq
of Lu-PSMA-617 every 6 weeks, for up to a maximum of
177
We report here the development and evaluation of six cycles. NOX66 was administered as a suppository on
the traffic light workflow (TLW), a novel, quantitative days 1–10 of each cycle according to the dose-escalation
imaging workflow for tracking lesional changes in tumor protocol. 6
volume and PSMA maximum standardized uptake value
(SUV ). TLW patterns of response and progression 2.3. Imaging procedures and analysis
max
were correlated with clinical outcomes in a clinical trial PSMA PET/CT scans were performed at pre- and
of 177 Lu-PSMA-617. We compared our TLW with the post-treatment (after completing all six cycles or when
6
Response Evaluation Criteria in PSMA PET (RECIP treatment was ceased), as described previously. Pre- and
10
1.0) and discuss the ongoing development of PSMA PET post-treatment diagnostic CT and whole-body bone
response assessment criteria. scintigraphy were also performed.
2. Materials and methods 2.4. Quantitative analysis

LuPIN, a single-center, phase 1/2 study, evaluated PSMA PET imaging analysis was performed using
TM
177 Lu-PSMA-617 combined with NOX66 in metastatic MIM Encore , version 7.1 (MIM Software Inc., USA).
castration-resistant prostate cancer (mCRPC) patients A standardized, semi-automated workflow identified
who had progressed on taxane chemotherapy and regions of interest with standardized uptake value (SUV)
an androgen-signaling inhibitor (ASI). The clinical ≥3. Following semi-automated segmentation, a nuclear
outcomes of the trial have been reported previously. The medicine physician reviewed and excluded any uptake
7,8

Volume 3 Issue 3 (2025) 44 doi: 10.36922/ARNM025110011