Estimation of [177Lu]PSMA-617 tumor uptake based on voxel-wise 3D Monte Carlo tumor dosimetry in patients with metastasized castration resistant prostate cancer

2020 ◽  
Vol 59 (05) ◽  
pp. 365-374
Author(s):  
Theresa Ida Götz ◽  
Elmar Wolfgang Lang ◽  
Olaf Prante ◽  
Michael Cordes ◽  
Torsten Kuwert ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Monte Carlo ◽  
Three Dimensional ◽  
Absorbed Dose ◽  
Whole Body ◽  
Patient Specific ◽  
Average Dose ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Before And After

Abstract Objective Patients with advanced prostate cancer are suitable candidates for [177Lu]PSMA-617 therapy. Integrated SPECT/CT systems have the potential to improve the accuracy of patient-specific tumor dosimetry. We present a novel patient-specific Monte Carlo based voxel-wise dosimetry approach to determine organ and total tumor doses (TTD). Methods 13 patients with histologically confirmed metastasized castration-resistant prostate cancer were treated with a total of 18 cycles of [177Lu]PSMA-617 therapy. In each patient, dosimetry was performed after the first cycle of [177Lu]PSMA-617 therapy. Regions of interest were defined manually on the SPECT/CT images for the kidneys, spleen and all 295 PSMA-positive tumor lesions in the field of view. The absorbed dose to normal organs and to all tumor lesions were calculated by a three dimensional dosimetry method based on Monte Carlo Simulations. Results The average dose values yielded the following results: 2.59 ± 0.63 Gy (1.67–3.92 Gy) for the kidneys, 0.79 ± 0.46 Gy (0.31–1.90 Gy) for the spleen and 11.00 ± 11.97 Gy (1.28–49.10 Gy) for all tracer-positive tumor lesions. A trend towards higher TTD was observed in patients with Gleason Scores > 8 compared to Gleason Scores ≤ 8 and in lymph node metastases compared to bone metastases. A significant correlation was determined between the serum-PSA level before RLT and the TTD (r = –0.57, p < 0.05), as well as between the TTD with the percentage change of serum-PSA levels before and after therapy was observed (r = –0.57, p < 0.05). Patients with higher total tumor volumes of PSMA-positive lesions demonstrated significantly lower kidney average dose values (r = –0.58, p < 0.05). Conclusion The presented novel Monte Carlo based voxel-wise dosimetry calculates a patient specific whole-body dose distribution, thus taking into account individual anatomies and tissue compositions showing promising results for the estimation of radiation doses of normal organs and PSMA-positive tumor lesions.

scholarly journals PSMA Expression Predicts Early Biochemical Response in Patients with Metastatic Castration-Resistant Prostate Cancer under 177Lu-PSMA-617 Radioligand Therapy

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2938
Author(s):  
Liam Widjaja ◽  
Rudolf A. Werner ◽  
Tobias L. Ross ◽  
Frank M. Bengel ◽  
Thorsten Derlin
Keyword(s):  
Prostate Cancer ◽  
Whole Body ◽  
Biochemical Response ◽  
Clinical Parameters ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Castration Resistant ◽  
Psa Response ◽  
High Age ◽  
Psma Expression

177Lu-Prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) is a promising treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the predictive value of pretherapeutic PSMA-ligand positron emission tomography (PET) and established clinical parameters for early biochemical response after two cycles of RLT. In total, 71 mCRPC patients who had undergone PET/computed tomography (CT) with 68Ga-PSMA-11 prior to two cycles of 177Lu-PSMA-617 RLT were included. Malignant lesions on pretherapeutic PET/CTs were manually segmented and average maximum PSMA expression (maximum standardized uptake values, SUVmax), whole-body PSMA-tumor volume (TV), and whole-body total lesion (TL)-PSMA were calculated. We then tested the predictive performance of these parameters for early biochemical response (defined as prostate-sepcific antigen (PSA) decrease of ≥50% according to PCWG2) after two cycles of RLT, relative to established clinical parameters. Early PSA response was observed in 34/71 patients. PSA change after two cycles of RLT correlated with pretherapeutic SUVmax (r = −0.49; p < 0.001), but not with PSMA-TV (r = 0.02; p = 0.89) or TL-PSMA (r = −0.15; p = 0.22). A cut-off of 19.8 for SUVmax and 75.5 years for age was defined by receiver operating characteristics and revealed a significant outcome difference for early biochemical response between patients with adversely low vs. high PSMA expression and low vs. high age (p < 0.001). Multivariate analysis identified SUVmax (HR, 7.94, p = 0.001) and age (HR, 8.05, p = 0.002) as independent predictors for PSA response early in the treatment course. Thus, high age and high PSMA expression in patients scheduled for RLT identify patients with early biochemical response. This study provides a rationale for further prospective studies exploring PET-guided treatment intensification in selected patients.

scholarly journals Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC

2020 ◽  
Author(s):  
Vasko Kramer ◽  
René Fernández ◽  
Wencke Lehnert ◽  
Luis David Jiménez-Franco ◽  
Cristian Soza-Ried ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Whole Body ◽  
Published Data ◽  
Albumin Binding ◽  
Castration Resistant Prostate Cancer ◽  
Effective Treatment Option ◽  
Binding Properties ◽  
Castration Resistant ◽  
Red Marrow ◽  
Therapeutic Outcomes

Abstract Introduction PSMA-targeted radionuclide therapy with lutetium-177 has emerged as an effective treatment option for metastatic, castration-resistant prostate cancer (mCRPC). Recently, the concept of modifying PSMA radioligands with an albumin-binding entity was demonstrated as a promising measure to increase the tumor uptake in preclinical experiments. The aim of this study was to translate the concept to a clinical setting and evaluate the safety and dosimetry of [177Lu]Lu-PSMA-ALB-56, a novel PSMA radioligand with albumin-binding properties. Methods Ten patients (71.8 ± 8.2 years) with mCRPC received an activity of 3360 ± 393 MBq (120–160 μg) [177Lu]Lu-PSMA-ALB-56 followed by whole-body SPECT/CT imaging over 7 days. Volumes of interest were defined on the SPECT/CT images for dosimetric evaluation for healthy tissue and tumor lesions. General safety and therapeutic efficacy were assessed by measuring blood biomarkers. Results [177Lu]Lu-PSMA-ALB-56 was well tolerated, and no severe adverse events were observed. SPECT images revealed longer circulation of [177Lu]Lu-PSMA-ALB-56 in the blood with the highest uptake in tumor lesions at 48 h post injection. Compared with published data for other therapeutic PSMA radioligands (e.g. PSMA-617 and PSMA I&T), normalized absorbed doses of [177Lu]Lu-PSMA-ALB-56 were up to 2.3-fold higher in tumor lesions (6.64 ± 6.92 Gy/GBq) and similar in salivary glands (0.87 ± 0.43 Gy/GBq). Doses to the kidneys and red marrow (2.54 ± 0.94 Gy/GBq and 0.29 ± 0.07 Gy/GBq, respectively) were increased. Conclusion Our data demonstrated that the concept of albumin-binding PSMA-radioligands is feasible and leads to increased tumor doses. After further optimization of the ligand design, the therapeutic outcomes may be improved for patients with prostate cancer.

Quantitative bone scan lesion area as an early surrogate outcome measure indicative of overall survival in metastatic castration-resistant prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 179-179
Author(s):  
Matthew S. Brown ◽  
Hyun J. Kim ◽  
Gregory H. Chu ◽  
Martin Allen-Auerbach ◽  
Cheryce Fischer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Bone Scan ◽  
Post Treatment ◽  
Whole Body ◽  
Treatment Trial ◽  
Castration Resistant Prostate Cancer ◽  
Lesion Area ◽  
Surrogate Outcome ◽  
Castration Resistant

179 Background: Bone Scan Lesion Area (BSLA) is a biomarker that can be computed semi-automatically from whole-body scintigraphic imaging as a measure of overall bone tumor burden. Initial development and validation, including correlation with outcomes, was performed in trial cohorts from a single drug treatment with controls in subjects with metastatic castrate-resistant prostate cancer (CRPC). A 30% increase/decrease in BSLA was defined as progression/response on bone scan. We hypothesize that, when applied to an independent treatment trial cohort with a different mechanism of drug action, baseline BSLA and Week 12 change post-treatment are predictive of a subject's overall survival. Methods: From an anonymized imaging research database a cohort of 198 CRPC subjects was identified who enrolled in a treatment trial (127 treated, 71 placebo). This cohort was independent of those used for biomarker development and initial validation, and involved a different mechanism of drug action. Subjects underwent standard of care whole-body bone scintigraphy with 99mTc-Methyl diphosphonate (99mTc-MDP). BSLA was calculated at baseline and response at Week 12. Multivariate Cox regression was used to test whether (1) baseline BSLA, and (2) early changes in BSLA (12 weeks post treatment) were predictive of overall survival. Results: BSLA < 2000 mm2 at baseline was a prognostic factor (HR=0.6; p=0.003) and predictive of longer survival (HR=0.4; p<0.001). Subjects without PD by BSLA at Week 12 had significantly longer survival than subjects with PD: median 170 days vs. 186 days in the placebo group and 260 days vs. 392 days in the treatment group. The overall survival rates between non-PD and PD subjects were statistically different (HR=0.64, p=0.007). Conclusions: BSLA is calculated semi-automatically from bone scans and provides a quantitative and objective treatment response assessment. Baseline BSLA and early changes post treatment were found to be predictive of overall survival in patients with metastatic castration-resistant prostate cancer. BSLA has now been demonstrated to be an early surrogate outcome for overall survival in different drug treatments.

scholarly journals Selective Intra-Arterial 177Lu-PSMA Therapy for Castration Resistant Prostate Cancer: Preliminary Results of a Pilot Study

2021 ◽  
Author(s):  
Haluk Sayman ◽  
Fatih Gulsen ◽  
Sait Sager ◽  
Elife Akgun ◽  
Nami Yeyin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Pilot Study ◽  
Prostate Gland ◽  
Whole Body ◽  
Castration Resistant Prostate Cancer ◽  
Preliminary Results ◽  
Administration Routes ◽  
Castration Resistant ◽  
Metastatic Lesions ◽  
Cerrahpasa Medical Faculty

Abstract Purpose177Lu-PSMA is a promising therapy for patients with metastatic castration resistant prostate cancer patients (mCRPC). To our knowledge, no study has compared the pharmacokinetic profiles of 177Lu-PSMA therapy delivered intra-arterially. We aimed to compare the feasibility and safety of selective intra-arterial (IA) administration vs conventional intravenous (IV) administration of 177Lu-PSMA in mCRPC. MethodsIn this within-patient pilot study, four patients (median age, 62.5; range, 53-72) with mCRPC who were referred to our clinic between January 2018 and September 2019 for treatment with 177Lu-PSMA. Patients were treated in two visits; in each visit receiving half of the total empiric therapeutic dose of 200 mCi, IV at the first visit and IA at the second visit. They were followed upto 8 weeks using routine parameters such as hematological status, renal function, and serum PSA levels. For each patient, organ biodistribution in lesions, kidneys, liver, bone marrow, prostate, and whole body was calculated for both administration routes according to the Medical Internal Radiation Dose (MIRD) schema. Mean absorbed doses (MAD) across all patients were compared between both administration routes. ResultsThe MAD of all metastatic lesions was significantly higher by IA vs IV administration (1.59 vs 1.20 MGy/MBq; p=0.024). The prostate gland had a lower MAD between IA and IV administrations, but the difference was not significant (0.27 vs 0.36 MGy/MBq; p=0.22). Patients tolerated IA administration very well without unexpected side effects. ConclusionThese preliminary results of an ongoing study showed that IA 177Lu-PSMA therapy is feasible and safe to treat metastatic lesions, potentially having a higher delivery efficacy compared to IV administration.This study is approved by Cerrahpasa Medical Faculty ethics committee on March 5, 2019 and retrospectively registered with file no: 83045809-604.01.02.

Impact of the introduction of novel hormonal agents on metastatic castration-resistant prostate cancer treatment choice

2019 ◽  
Vol 26 (2) ◽  
pp. 293-305 ◽  
Author(s):  
Halima Lahcene ◽  
Armen G Aprikian ◽  
Marie Vanhuyse ◽  
Jason Hu ◽  
Franck Bladou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Public Funding ◽  
Cancer Registries ◽  
Castration Resistant Prostate Cancer ◽  
University Hospitals ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Before And After ◽  
Mcgill University

Background Docetaxel-based chemotherapy has been the cornerstone of the management of symptomatic metastatic castration-resistant prostate cancer (mCRPC) since 2004. This study aimed to describe how real-world clinical practice was changed with the public funding of novel hormonal agents (abiraterone and enzalutamide) in Quebec. Methods We conducted a retrospective cohort study in two McGill University hospitals. Hospital-based cancer registries were used to select mCRPC patients in medical oncology departments from January 2010 to June 2014. Two groups according to mCRPC diagnosis year were built, with 2012 chosen as the cut-off year, corresponding to the year abiraterone was approved for public reimbursement in second-line in Quebec. Kaplan–Meier analysis was used to estimate time to first docetaxel prescription since mCRPC diagnosis before and after 2012. Cox regression was used to identify predictive factors of docetaxel and novel hormonal agent use. Results In our cohort, 308 patients diagnosed with mCRPC were selected with 162 patients in the pre-2012 group and 146 patients in the post-2012 group. The median age at mCRPC was 74.0 years old. At 12 months from diagnosis, 69% of patients received a prescription for docetaxel in the pre-2012 group comparatively to 53% in the post-2012 group. Factors that decreased the likelihood of docetaxel utilization were: age older than 80 at mCRPC diagnosis (HR: 0.5; 95%CI: 0.3–0.7), mCRPC diagnosis after 2012 (HR: 0.6; 95%CI: 0.4–0.8), and asymptomatic disease at mCRPC diagnosis (HR: 0.5; 95%CI: 0.3–0.7). Conclusion The introduction of novel hormonal agents reduced first-line and overall docetaxel utilization and delayed time to its initiation.

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