Repeated ¹⁷⁷Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq

Abstract

Current treatment protocols for 177Lu-PSMA-617 therapies were cautiously derived from dosimetry data, but their practical appropriateness have not yet been proven clinically.We retrospectively report our clinical observations using four different treatment activities. Methods: Forty patients with advanced prostate cancer and positive uptake in PSMA-imaging were treated in fractions of 4 GBq / 80 nmol, 6 GBq / 120 nmol, 7.4 GBq / 150 nmol or 9.3 GBq / 150 nmol 177 Lu-activity / precursor-amount (n=10, respectively) every 2 months. Safety lab was checked every 2 weeks, PSA-response every 4 weeks; other effects were assessed per anamnesis. Results: Initial PSA response presented no correlation to treatment activity. However, 2/10, 4/10, 4/10 and 7/10 patients with doses of 4, 6, 7.4 and 9.3 GBq were in partial remission 8 weeks after completing all 3 cycles;This would be in line with, but due to low patient numbers not proving, a positive doseresponse-relationship. Acute hematological toxicity was also irrespective of treatment activity and no more than one grade-3/4 toxicity was observed in each group.Nevertheless, in contrast to the other groups the mean platelet count in the 9. (8,12). Nevertheless, tolerance limits for normal organs reported in the literature are based on external beam radiotherapy and have only been extrapolated to RLT using radiobiological models, which themselves have manifold limitations as reviewed recently (13). Thus, dosimetry in nuclear medicine can only approximate a guidance level for dosing RLT but the optimal treatment regime has still to be refined clinically.In this retrospective analysis we report our clinical experience with fractions of 4 GBq, 6GBq, 7.4 GBq or 9.3 GBq 177 Lu-PSMA-617 repeated every 2 months.by on May 10, 2018. For personal use only. jnm.snmjournals.org Downloaded from MATERIALS AND METHODS Patients 177Lu-PSMA-RLT was performed under the conditions of the updated declaration of Helsinki, § 37 (Unproven interventions in clinical practice) and in accordance to the German Pharmaceuticals Law §13(2b) as a salvage therapy for patients with mCRPC, which had to be resistant against or ineligible for approved options and presented with progressive disease. Patient selection is outlined in Fig. 1. For patients stratified to 177 Lu-PSMA-617, each dose level was administered to 10 consecutive patients. If toxicities were comparable to the placebo group of the ALSYMPCA-trial (14), individual dose escalations for non-responders were considered ethically justified, resulting in a short learning-phase using heterogeneous dosing regimens between respective dose escalation groups. Data of these heterogeneous interim patients were not suitable for this kind of systematical evaluation, nevertheless some have been made public available within other publications (8,15). The chronology how this dose escalation was embedded into clinical practice is summarized in Fig. 2. Patient characteristics were summarized in (Table 1). All patients were informed about the experime...

Clinical outcome of standardized 177Lu-PSMA-617 therapy in metastatic prostate cancer patients receiving 7400 MBq every 4 weeks

“…3 Kaplan-Meier survival plot of the patients stratified by PSA response. In comparison to patients with no PSA decline, patients with any PSA reduction up to 50% and more lived significantly longer (median survival not reached vs. 52 weeks, P < 0.0001) PSMA-RLT doses, as this has also been shown by Rathke et al [23] and could encourage systematic dose-finding studies for this treatment.…”

Variability in lutetium-177 SPECT quantification between different state-of-the-art SPECT/CT systems

“…The spheres and background compartment were filled with a homogeneous solution of 177 Lu in water with an activity concentration of approximately 750 kBq/ml for the spheres and 75 kBq/ml for the background compartment, resulting in a sphere-to-background ratio of 10:1. The concentrations were based upon the expected lesion uptake in lutetium therapy [2,26]. The solution was saturated with a 50 mM ethylenediaminetetraacetic acid (EDTA) solution to prevent precipitation of lutetium.…”

Radioligand therapy using [177Lu]Lu-PSMA-617 in mCRPC: a pre-VISION single-center analysis

“…Thus, a formal dose-escalating study to define a dose with an optimal efficacy-toxicity profile has not been done to this day. Additionally, transferability of the results of Rathke et al to the clinical routine is impaired, as patients with end-stage mCRPC are rather evaluated for [ 225 Ac]Ac-PSMA ligands and therefore not included in the analysis [19]. Moreover, only 40-50% of enrolled patients had received taxane chemotherapy, which is violating the VISION trial enrollment criteria.…”