Article Figures & Data
Figures
- FIGURE 1.
PSMA equals enzyme glutamate carboxypeptidase II. Its proteolytic domain can be targeted with Glu-urea motif (green). Hydrophobic pocket accessory to proteolytic domain adversely interacts with highly polar chelates such as DOTA (red) but favors more lipophilic chelates (orange) such as CIM (MIP-1427) for labeling with 99mTc or HBED-CC (PSMA-11) for labeling with 68Ga. In PSMA-617, aromatic linker (yellow) exploits lipophilic accessory pocket to keep more universal DOTA-chelate remote to Glu-urea binding site.
- FIGURE 2.
(A) Waterfall graph presenting PSA response after 1 cycle of 177Lu-PSMA-617 therapy. (B) Waterfall graph presenting PSA response after 3 cycles of therapy. (C) Follow-up between PSA response after cycle 1 and cycle 3.
- FIGURE 3.
Imaging-based response evaluation. (A) 68Ga-PSMA-11 PET was evaluated semiquantitatively. (B) 99mTc-MIP1427 scintigraphy–enabled visual evaluation. (C) If target lesions were available, CT was evaluated in accordance to RECIST. GM = geometric mean; MIP = maximum-intensity projection; p.i. = after injection.
- FIGURE 4.
(A) PSMA PET/CT delivers highest resolution. (B) Coemission of γ-rays enables imaging during therapy. (C) 99mTc-PSMA scintigraphy has minimally less noise than posttherapy scanning and can be used for imaging follow-up in out-patient setting. GM = geometric mean; MIP = maximum-intensity projections; p.i. = after injection.
- FIGURE 5.
Course of white blood cell count (A) and platelets (B) during 177Lu-PSMA-617 therapy.
Tables
Patient no. Age (y) GS OP RTx CRPC Abirat Enza 223Ra CTx Cycles (GBq) Visceral metastases 1 68 7 1 B 1 0 0 0 D 6/6/6 Lung 2 71 4 0 L/B 1 1 1 0 D/C 4/4/4 Liver 3 75 9 1 B 1 0 0 0 0 4/4/6 0 4 61 8 1 L/B 1 1 0 0 D/Sorafenib 6/6/6 Liver 5 67 9 0 L/B 1 0 0 0 0 6/6/6 0 6 78 8 1 L/B 1 0 0 0 0 6/6/6 0 7 71 9 0 0 1 0 1 0 D/C/EMP/HU 4/PD Liver 8 78 7b 1 B 1 1 1 1 D/EMP 6 0 9 68 9 1 0 1 0 0 0 D 6/6/6 Brain 10 74 9 1 0 1 1 1 0 0 4/6/6 Liver 11 66 9 1 L 1 1 0 0 0 6/6/6 0 12 78 8 1 0 1 0 0 0 0 6/6 0 13 79 7b 1 0 1 0 0 1 0 3/Tox Lung, adrenal 14 73 9 1 B 1 1 1 0 0 4/6/6 Liver, adrenal 15 71 7 0 L 1 1 0 0 0 4/6 Liver 16 68 NA 0 0 1 1 0 1 D/EMP 6 0 17 73 NA 1 L/B 1 1 0 1 0 4/4 0 18 78 8 1 L 1 1 0 1 0 4/6/6 0 19 73 NA 1 L/B 1 1 0 0 D 4/Tox Lung 20 68 7 1 B 1 1 1 0 D 6 0 21 85 7a 1 B 1 1 1 0 D 6/6/ 0 22 71 7 0 L 1 1 0 0 0 4/PD Rectum 23 66 9 1 L/B 1 1 1 0 0 6/6 0 24 75 8 1 B 1 1 1 0 D 6 0 25 80 7 1 B 1 1 1 0 D/C 6 Liver, lung 26 64 9 0 B 1 1 0 1 0 6 0 27 61 9 1 L/B 1 1 1 0 D/C 6 Liver 28 69 8 1 L/B 1 1 0 0 0 6/6/ Lung 29 73 9 0 L 1 1 1 0 D 6/6 0 30 75 NA 1 L 1 0 1 0 0 6/Tox 0 GS = Gleason score; OP = prostatectomy; RTx = radiation therapy to prostate bed (= L) or bone (= B); CRPC = hormone therapy with both a luteinizing hormone-releasing hormone (LHRH) analog/antagonist and an antiandrogen; Abirat = abiraterone; Enza = enzalutamide; CTx = chemotherapy with docetaxel (= D), cabazitaxel (= C), estramustine monophosphate (= EMP), or hydroxyurea (= HU); Cycles = therapy with 177Lu-PSMA-617 with given activities (GBq) in bimonthly fractions; NA = not available.
Fractionated therapy had to be discontinued due to toxicity (= Tox) or progressive disease (= PD).
Patient–cycle Low Intermediate–low Intermediate–high High Tumor load P1-C1 (Gy/GBq) P1-C2 (Gy/GBq) P2-C1 (Gy/GBq) P2-C2 (Gy/GBq) P3-C1 (Gy/GBq) P3-C2 (Gy/GBq) P4-C1 (Gy/GBq) P4-C2 (Gy/GBq) Kidney 0.55 0.56 1.14 0.82 0.81 0.76 0.62 0.76 Red marrow 0.02 0.02 0.02 0.02 0.03 0.03 0.05 0.03 Parotid gland 2.2 1.16 1.03 0.82 1.26 1.3 1.27 1.17 Submandibular gland 1.3 1.69 1.26 0.97 1.37 1.31 1.82 2.13 Liver 0.09 0.1 0.07 0.06 0.09 0.1 0.16 0.13 Spleen 0.19 0.15 0.26 0.14 0.11 0.13 0.28 0.27 Bladder wall 0.03 0.16 0.16 0.17 0.29 0.23 0.41 0.36 Metastases (mean) 6.1 22.8 15.3 14 Effective dose equivalent (mSv/GBq) 81.8 77 114 82.5 96.3 91.2 126 111 Effective dose (mSv/GBq) 48.2 46.5 37.2 43.9 58.3 54.3 83,4 65
Supplemental Data
Files in this Data Supplement:
Jump to section
Related Articles
Cited By...
- Best Patient Care Practices for Administering PSMA-Targeted Radiopharmaceutical Therapy
- Dosimetry of [177Lu]Lu-PSMA-Targeted Radiopharmaceutical Therapies in Patients with Prostate Cancer: A Comparative Systematic Review and Metaanalysis
- Deescalated 225Ac-PSMA-617 Versus 177Lu/225Ac-PSMA-617 Cocktail Therapy: A Single-Center Retrospective Analysis of 233 Patients
- Renal and Multiorgan Safety of 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer in the VISION Dosimetry Substudy
- Optimized Methods for the Production of High-Purity 203Pb Using Electroplated Thallium Targets
- Tandem Isotope Therapy with 225Ac- and 177Lu-PSMA-617 in a Murine Model of Prostate Cancer
- Evolution of Models of Prostate Cancer: Their Contribution to Current Therapies
- Novel Framework for Treatment Response Evaluation Using PSMA PET/CT in Patients with Metastatic Castration-Resistant Prostate Cancer (RECIP 1.0): An International Multicenter Study
- Pretherapeutic Comparative Dosimetry of 177Lu-rhPSMA-7.3 and 177Lu-PSMA I&T in Patients with Metastatic Castration-Resistant Prostate Cancer
- Effects of 225Ac-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis
- The History of Prostate-Specific Membrane Antigen as a Theranostic Target in Prostate Cancer: The Cornerstone Role of the Prostate Cancer Foundation
- An Improved 211At-Labeled Agent for PSMA-Targeted {alpha}-Therapy
- Radionuclide Therapy in Prostate Cancer: From Standalone to Combination PSMA Theranostics
- Dosimetry in Clinical Radiopharmaceutical Therapy of Cancer: Practicality Versus Perfection in Current Practice
- To Scan or Not to Scan: An Unnecessary Dilemma for PSMA Radioligand Therapy
- Safety of PSMA-Targeted Molecular Radioligand Therapy with 177Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312)
- TriTACs, a Novel Class of T-Cell-Engaging Protein Constructs Designed for the Treatment of Solid Tumors
- 177Lu-EB-PSMA Radioligand Therapy with Escalating Doses in Patients with Metastatic Castration-Resistant Prostate Cancer
- Digital Solid-State SPECT/CT Quantitation of Absolute 177Lu Radiotracer Concentration: In Vivo and In Vitro Validation
- 177Lu-NM600 Targeted Radionuclide Therapy Extends Survival in Syngeneic Murine Models of Triple-Negative Breast Cancer
- Radiation Dosimetry in 177Lu-PSMA-617 Therapy Using a Single Posttreatment SPECT/CT Scan: A Novel Methodology to Generate Time- and Tissue-Specific Dose Factors
- JHU-2545 Selectively Shields Salivary Glands and Kidneys during PSMA-Targeted Radiotherapy
- Long-Term Follow-up and Outcomes of Retreatment in an Expanded 50-Patient Single-Center Phase II Prospective Trial of 177Lu-PSMA-617 Theranostics in Metastatic Castration-Resistant Prostate Cancer
- Theranostics: Leveraging Molecular Imaging and Therapy to Impact Patient Management and Secure the Future of Nuclear Medicine
- Hybrid Tracers Based on Cyanine Backbones Targeting Prostate-Specific Membrane Antigen: Tuning Pharmacokinetic Properties and Exploring Dye-Protein Interaction
- Development of Novel PSMA Ligands for Imaging and Therapy with Copper Isotopes
- 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer Patients with a Single Functioning Kidney
- Imaging Patients with Metastatic Castration-Resistant Prostate Cancer Using 89Zr-DFO-MSTP2109A Anti-STEAP1 Antibody
- Is the Vision of Radioligand Therapy for Prostate Cancer Becoming a Reality? An Overview of the Phase III VISION Trial and Its Importance for the Future of Theranostics
- Effect of External Cooling on 177Lu-PSMA Uptake by the Parotid Glands
- First Clinicopathologic Evidence of a Non-PSMA-Related Uptake Mechanism for 68Ga-PSMA-11 in Salivary Glands
- Clinical Outcomes of 177Lu-PSMA Radioligand Therapy in Earlier and Later Phases of Metastatic Castration-Resistant Prostate Cancer Grouped by Previous Taxane Chemotherapy
- Dosimetry Estimate and Initial Clinical Experience with 90Y-PSMA-617
- Modeling and Predicting Tumor Response in Radioligand Therapy
- The Relevance of Dosimetry in Precision Medicine
- Detection Threshold and Reproducibility of 68Ga-PSMA11 PET/CT in a Mouse Model of Prostate Cancer
- Predictive Factors of Response and Overall Survival in Patients with Castration-Resistant Metastatic Prostate Cancer Undergoing 177Lu-PSMA Therapy
- The Effect of Total Tumor Volume on the Biologically Effective Dose to Tumor and Kidneys for 177Lu-Labeled PSMA Peptides
- PSMA-Targeted Radionuclide Therapy and Salivary Gland Toxicity: Why Does It Matter?
- Targeted {alpha}-Therapy of Metastatic Castration-Resistant Prostate Cancer with 225Ac-PSMA-617: Swimmer-Plot Analysis Suggests Efficacy Regarding Duration of Tumor Control
- Repeated 177Lu-Labeled PSMA-617 Radioligand Therapy Using Treatment Activities of Up to 9.3 GBq
- Low-Level Endogenous PSMA Expression in Nonprostatic Tumor Xenografts Is Sufficient for In Vivo Tumor Targeting and Imaging
- Why Targeting PSMA Is a Game Changer in the Management of Prostate Cancer
- Establishing 177Lu-PSMA-617 Radioligand Therapy in a Syngeneic Model of Murine Prostate Cancer
- Targeted {alpha}-Therapy of Metastatic Castration-Resistant Prostate Cancer with 225Ac-PSMA-617: Dosimetry Estimate and Empiric Dose Finding
- Glu-Ureido-Based Inhibitors of Prostate-Specific Membrane Antigen: Lessons Learned During the Development of a Novel Class of Low-Molecular-Weight Theranostic Radiotracers
- Dual-Target Binding Ligands with Modulated Pharmacokinetics for Endoradiotherapy of Prostate Cancer
- Prostate-Specific Membrane Antigen Ligands for Imaging and Therapy
- Acceleration of PSMA-Targeted Theranostics to the Clinic: Can Common Sense Prevail?
- Why Targeting of PSMA Is a Valuable Addition to the Management of Castration-Resistant Prostate Cancer: The Urologists Point of View
- 177Lu-PSMA Radioligand Therapy for Prostate Cancer
- Semiquantitative Parameters in PSMA-Targeted PET Imaging with 18F-DCFPyL: Variability in Normal-Organ Uptake
- 68Ga-PSMA-11 PET as a Gatekeeper for the Treatment of Metastatic Prostate Cancer with 223Ra: Proof of Concept
- Preclinical Evaluation of 18F-PSMA-1007, a New Prostate-Specific Membrane Antigen Ligand for Prostate Cancer Imaging
- Radiation Dosimetry for 177Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: Absorbed Dose in Normal Organs and Tumor Lesions
- Predictors of Response to Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with 177Lu-PSMA-617
- German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients
- 68Ga-PSMA-11 PET Imaging of Response to Androgen Receptor Inhibition: First Human Experience
- PSMA-Based Radioligand Therapy for Metastatic Castration-Resistant Prostate Cancer: The Bad Berka Experience Since 2013
- The Rise of PSMA Ligands for Diagnosis and Therapy of Prostate Cancer
- Imaging approaches to optimize molecular therapies