Introduction
Materials and methods
Ethical and regulatory issues
Patient selection
Patient | Age | Previous therapies | ||||||
---|---|---|---|---|---|---|---|---|
Surgery | Radiotherapy | Chemotherapy | Monoclonal anti-body | Hormonal therapy | Supportive therapy |
223Ra (MBq) | ||
1 | 75 | Prostatectomy Vesiculectomy | External beam radiation therapy | / | / | Degarelix + bicalutamide | Zoledronic acid | / |
2 | 76 | Prostatectomy | / | / | / | Leuprorelin | / | / |
3 | 61 | / | External beam radiation therapy | Docetaxel | / | Degarelix + bicalutamide + dutasteride; degarelix; enzalutamide + degarelix | / | 24.4 |
4 | 68 | / | / | / | / | Bicalutamide + leuprorelin | / | / |
5 | 63 | Prostatectomy | External beam radiation therapy | / | Denosumab | Abiraterone + leuprorelin | / | 18.1 |
6 | 74 | Palliative prostatectomy, decompression 14/15 | / | / | / | Goserelin + enzatulamide | Zoledronic acid | / |
7 | 59 | Prostatectomy | / | Taxotere | Denosumab | Bicalutamide + tamoxifene; abiraterone; enzalutamide | Zoledronic acid | / |
8 | 56 | / | / | Taxotere | Denosumab | Degarelix; pamorelin; leuprorelin | / | 26.3 |
9 | 66 | Prostatectomy Vesiculectomy | / | / | Denosumab | Leuprorelin; pamorelin | / | / |
10 | 82 | Prostatectomy | Proton therapy | / | Denosumab | Leuprorelin; enzalutamide | / | / |
Preparation of radiolabeled PSMA-targeting ligands
Preparation of 177Lu-PSMA617
Preparation of 68Ga-PSMA-HBED-CC
Administration of 177Lu-PSMA617 and safety procedures
Response assessment
68Ga-PSMA-HBED-CC PET/CT imaging and SUVmax analysis
18F-NaF PET/CT imaging
177Lu-PSMA617 whole-body imaging and dosimetry calculation
Statistics
Results
Evaluation of 177Lu-PSMA617 wholebody scans and dosimetry
Patient | Red marrow | Lacrimal glands | Parotid glands | Sub-mandibular glands | Kidneys | Urinary bladder wall | Osteogenic cells | Spleen | Liver | Small intestine | Gallbladder wall | Pancreas | ULI wall | LLI wall | Effective dose ImSv/M13q) | Skeletal metastases | Lymph node metastases | Visceral metastases |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 0.027 | 0.680 | 0.390 | 0.460 | 0.674 | 0.687 | 0.079 | 0.089 | 0.048 | 0.027 | 0.028 | 0.028 | 0.027 | 0.028 | 0.063 | 1.700 | / | / |
2 | 0.024 | 0.500 | 0.600 | 0.460 | 0.970 | 0.137 | 0.060 | 0.179 | 0.110 | 0.025 | 0.027 | 0.026 | 0.025 | 0.024 | 0.046 | 3.680 | / | / |
3 | 0.070 | 0.800 | 0.250 | 0.660 | 1.390 | 0.127 | 0.255 | 0.079 | 0.256 | 0.078 | 0.082 | 0.081 | 0.078 | 0.077 | 0.117 | 3.120 | / | / |
4 | 0.018 | 1.100 | 0.450 | 0.220 | 0.319 | 0.017 | 0.045 | 0.186 | 0.082 | 0.017 | 0.019 | 0.019 | 0.017 | 0.017 | 0.024 | 2.300 | / | / |
5 | 0.074 | 2.700 | 0.750 | 0.650 | 0.614 | 0.145 | 0.128 | 0.185 | 0.087 | 0.342 | 0.042 | 0.042 | 0.044 | 0.041 | 0.056 | 5.510 | / | / |
6 | 0.027 | 0.630 | 0.850 | 0.630 | 0.457 | 0.149 | 0.069 | 0.020 | 0.119 | 0.019 | 0.021 | 0.020 | 0.019 | 0.019 | 0.041 | 1.700 | 2.850 | 1.700 |
7 | 0.096 | 0.860 | 0.500 | 0.580 | 0.109 | 0.336 | 0.411 | 0.096 | / | 0.100 | 0.147 | 0.117 | 0.104 | 0.094 | 0.264 | 7.170 | / | 3.250 |
8 | 0.017 | 1.300 | 1.040 | 0.440 | 0.638 | 0.127 | 0.059 | 0.023 | 0.125 | 0.023 | 0.025 | 0.024 | 0.023 | 0.022 | 0.046 | 4.950 | / | / |
9 | 0.0453 | / | 0.420 | / | 0.372 | 0.229 | 0.182 | 0.061 | 0.123 | 0.062 | 0.063 | 0.063 | 0.062 | 0.062 | 0.076 | 1.100 | / | 2.350 |
10 | 0.0246 | 0.480 | 0.360 | 0.380 | 0.461 | 0.262 | 0.083 | 0.317 | 0.093 | 0.030 | 0.031 | 0.031 | 0.030 | 0.030 | 0.050 | 2.800 | 2.250 | / |
Min | 0.017 | 0.480 | 0.250 | 0.220 | 0.109 | 0.017 | 0.045 | 0.020 | 0.048 | 0.017 | 0.019 | 0.019 | 0.017 | 0.017 | 0.024 | 1.100 | 2.250 | 1.700 |
Mean | 0.042 | 1.006 | 0.561 | 0.498 | 0.600 | 0.222 | 0.137 | 0.123 | 0.116 | 0.072 | 0.048 | 0.045 | 0.043 | 0.041 | 0.078 | 3.403 | 2.550 | 2.433 |
Max | 0.096 | 2.700 | 1.040 | 0.660 | 1.390 | 0.687 | 0.411 | 0.317 | 0.256 | 0.342 | 0.147 | 0.117 | 0.104 | 0.094 | 0.264 | 7.170 | 2.850 | 3.250 |
Standard deviation | 0.028 | 0.690 | 0.248 | 0.146 | 0.362 | 0.185 | 0.117 | 0.092 | 0.058 | 0.099 | 0.040 | 0.032 | 0.029 | 0.027 | 0.070 | 1.940 | 0.424 | 0.778 |
Response evaluation of 177Lu-PSMA617 therapy
Patient | Accumulated activity GBq | Number of cycles | Therapy-related side effects | Response visceral and lymph node metastases | Response skeletal metastases | PSA before therapy | PSA after therapy | Overall response | ||
---|---|---|---|---|---|---|---|---|---|---|
Hematoxicity (grade) | Hepatotoxicity (grade) | Nephrotoxicity (grade) | ||||||||
1 | 17.7 | 3 | I → I | I → I | 0 | PR | PD | 264 | 531 | PD |
2 | 19.3 | 3 | 0 | I → I | I → I | PR | MX | 24.49 | 3.7 | MX |
3 | 18.6 | 3 | I → I | I → I | 0 | MX | MX | 482 | 92 | MX |
4 | 16.3 | 3 | 0 | 0 | 0 | PR | MX | 22 | 21 | MX |
5 | 17.9 | 3 | I → I | I → I | 0 | PR | PR | 13.7 | 7.1 | PR |
6 | 18.1 | 3 | 0 | I → I | 0 | PR | PR | 1338 | 821.1 | PR |
7 | 18.8 | 3 | 0 | I → I | 0 | PR | PR | 873 | 2493 | PR |
8 | 12.7 | 2 | I → I | I → I | I → II | SD | PD | 140 | 719 | PD |
9 | 18.6 | 3 | II → II | II → II | 0 | PD | PD | 119 | 197 | PD |
10 | 18.4 | 3 | 0 | I → I | 0 | PR | SD | 4.7 | 3 | SD |
Comparison of absorbed doses and SUVmax values
Skeletal metastases | Lymph node metastases | Visceral metastases | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Absorbed dose | SUVmax
| Absorbed dose | SUVmax
| Absorbed dose | SUVmax
| ||||||||||||
Patient | Therapy cycles | Accumulated activity (GBq) | D/Aa (Gy/GBq) | Dt0t
b (Gy) | Baseline | After two cycles | After three cycles | D/Aa (Gy/GBq) | Dt0t
b (Gy) | Baseline | After two cycles | After three cycles | D/Aa (Gy/GBq) | Dt0t
b (Gy) | Baseline | After two cycles | After three cycles |
1 | 3 | 17.7 | 1.70 | 30.16 | 12.40 | 11.98 | 9.78 | / | / | 16.50 | 3.33 | 7.93 | / | / | / | / | / |
2 | 3 | 19.3 | 3.68 | 71.17 | 21.53 | 8.40 | / | / | / | / | / | / | / | / | / | / | / |
3 | 3 | 18.6 | 3.12 | 58.13 | 18.12 | 11.00 | 11.97 | / | / | 20.88 | 4.60 | 2.95 | / | / | / | / | / |
4 | 3 | 16.3 | 2.30 | 37.49 | 8.00 | 5.40 | 5.49 | / | / | / | / | / | / | / | / | / | / |
5 | 3 | 17.9 | 5.51 | 98.52 | 9.60 | 5.58 | 5.40 | / | / | 4.10 | 1.20 | 1.10 | / | / | / | / | / |
6 | 3 | 18.1 | 1.70 | 30.80 | 30.37 | 28.87 | 22.07 | 2.85 | 51.64 | 16.00 | 21.80 | 22.50 | 1.70 | 30.80 | 28.55 | 34.25 | 24.70 |
7 | 3 | 18.8 | 7.17 | 135.01 | 27.65 | 18.83 | 14.10 | / | / | / | / | / | 3.25 | 61.20 | 16.90 | 12.20 | 14.60 |
8 | 2 | 12.7 | 4.95 | 62.87 | 9.99 | 12.79 | / | / | / | / | / | / | / | / | / | / | / |
9 | 3 | 18.6 | 1.10 | 20.45 | 28.93 | 15.63 | / | / | / | / | / | / | 2.35 | 43.69 | 24.10 | 17.75 | / |
10 | 3 | 18.4 | 2.80 | 51.41 | 35.65 | 31.58 | / | 2.25 | 41.31 | 21.43 | 12.48 | / | / | / | / | / | / |
Mean | 3.40 | 59.60 | 20.22 | 15.01 | 11.47 | 2.55 | 46.48 | 15.78 | 8.68 | 8.62 | 2.43 | 45.23 | 23.18 | 21.40 | 19.65 | ||
SD | 1.94 | 35.17 | 10.03 | 9.05 | 6.24 | 0.42 | 7.31 | 6.98 | 8.48 | 9.69 | 0.78 | 15.26 | 5.88 | 11.47 | 7.14 | ||
Minimum | 1.10 | 20.45 | 8.00 | 5.40 | 5.40 | 2.25 | 41.31 | 4.10 | 1.20 | 1.10 | 1.70 | 30.80 | 16.90 | 12.20 | 14.60 | ||
Maximum | 7.17 | 135.01 | 35.65 | 31.58 | 22.07 | 2.85 | 51.64 | 21.43 | 21.80 | 22.50 | 3.25 | 61.20 | 28.55 | 34.25 | 24.70 | ||
Max/min | 6.52 | 6.60 | 4.46 | 5.85 | 4.09 | 1.27 | 1.25 | 5.23 | 18.17 | 20.45 | 1.91 | 1.99 | 1.69 | 2.81 | 1.69 |
Safety evaluation
Parotid glands | Sub-mandibular glands | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Absorbed dose | Baseline | After three therapy cycles | Absorbed dose | Baseline | After three therapy cycles | |||||||||
Patient | Therapy cycles | Accumulated activity (GBq) | D/Aa (Gy/GBq) | Dtot
b (Gy) | SUVmax
| Volume (ml) | SUVmax
| Volume (ml) | D/Aa (Gy/GBq) | Dtot
b (Gy) | SUVmax
| Volume (ml) | SUVmax
| Volume (ml) |
1 | 3 | 17.74 | 0.39 | 6.92 | 26.00 | 27.00 | 15.45 | 21.40 | 0.46 | 8.16 | 19.65 | 8.65 | 11.45 | 8.00 |
2 | 3 | 19.34 | 0.60 | 11.60 | 14.40 | 29.23 | 10.55 | 22.25 | 0.46 | 8.90 | 16.80 | 7.57 | 11.35 | 6.10 |
3 | 3 | 18.63 | 0.25 | 4.66 | 9.35 | 24.65 | 8.45 | 21.00 | 0.66 | 12.30 | 12.45 | 9.05 | 13.85 | 6.85 |
4 | 3 | 16.30 | 0.45 | 7.34 | 10.25 | 18.75 | 10.20 | 14.95 | 0.22 | 3.59 | 10.35 | 9.40 | 10.65 | 9.10 |
5 | 3 | 17.88 | 0.75 | 13.41 | 7.85 | 25.75 | 10.05 | 19.80 | 0.65 | 11.62 | 8.35 | 7.45 | 10.25 | 6.15 |
6 | 3 | 18.12 | 0.85 | 15.40 | 17.80 | 22.35 | 10.35 | 21.50 | 0.63 | 11.42 | 23.15 | 9.85 | 14.20 | 8.20 |
7 | 3 | 18.83 | 0.50 | 9.42 | 14.95 | 18.90 | 16.95 | 15.80 | 0.58 | 10.92 | 17.50 | 9.30 | 18.25 | 8.05 |
8 | 2 | 12.70 | 1.04 | 13.21 | 7.50 | 34.00 | 7.00 | 26.00 | 0.44 | 5.59 | 9.05 | 7.30 | 7.45 | 6.10 |
9 | 3 | 18.59 | 0.42 | 7.81 | 8.05 | 25.70 | 8.75 | 17.30 | 7.00 | 7.35 | 4.75 | 7.25 | ||
10 | 3 | 18.36 | 0.36 | 6.61 | 7.80 | 23.50 | 18.70 | 0.38 | 6.98 | 9.40 | 10.35 | 17.50 | 11.95 | |
Mean | 0.56 | 9.64 | 12.40 | 24.98 | 11.65 | 20.00 | 0.50 | 8.83 | 13.37 | 8.63 | 11.97 | 7.78 | ||
SD | 0.25 | 3.56 | 5.99 | 4.59 | 3.95 | 3.48 | 0.15 | 3.02 | 5.52 | 1.13 | 4.17 | 1.79 | ||
Minimum | 0.25 | 4.66 | 7.50 | 18.75 | 7.00 | 14.95 | 0.22 | 3.59 | 7.00 | 7.30 | 4.75 | 6.10 | ||
Maximum | 1.04 | 15.40 | 26.00 | 34.00 | 18.70 | 26.00 | 0.66 | 12.30 | 23.15 | 10.35 | 18.25 | 11.95 | ||
Max/min | 4.16 | 3.31 | 3.47 | 1.81 | 2.67 | 1.74 | 3.00 | 3.43 | 3.31 | 1.42 | 3.84 | 1.96 |