Single Center Experience with a 4-Week 177Lu-PSMA-617 Treatment Interval in Patients with Metastatic Castration-Resistant Prostate Cancer

Background: 177Lu-PSMA-617 is a promising theragnostic treatment for metastatic castration-resistant prostate cancer (mCRPC). However, both the optimal treatment dose and interval in mCRPC and the rate of identification of responders from non-responders among possible treatment candidates are unknown. Methods: 62 men with mCRPC who were treated with 177Lu-PSMA-617 during 1/2017–2/2019 were included in the study. Treatment responses, overall survival (OS) and progression free survival (PFS) were determined. The median follow-up time was 1.4 years (IQR 0.5–2.2). Tumor volume of metastases (MTV), SUVmax and tumor lesion activity (TLA) were quantitated from pre-treatment PSMA PET/CT images together with pre-treatment PSA. Results: An average of three treatment cycles (2–5) were given within a four-week interval. PFS was 4.9 months (2.4–9.6) and OS was 17.2 months (6–26.4). There were no major adverse events reported. A significant PSA response of >50% was found in 58.7% of patients, which was significantly associated with longer OS, p < 0.004. PSA response was not associated with staging PSMA-derived parameters. Conclusions: 177Lu-PSMA-617 treatment in four-week intervals was safe and effective. Almost 60% of patients had a significant PSA response, which was associated with better OS. Pre-treatment PSA kinetics or staging PSMA PET/CT-derived parameters were not helpful in identifying treatment responders from non-responders; better biomarkers are needed to aid in patient selection.© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).fi=vertaisarvioitu|en=peerReviewed

Imaging of accidental contamination with F-18-solution; a quick trouble-shooting procedure

To the best of our knowledge, imaging of accidental exposure to radioactive fluorine-18 (F-18) due to liquid spill has not been described earlier in the scientific literature. The short half-life of F-18 (t½=110 min), current radiation safety requirements, and Good Manufacturing Practice (GMP) regulations on radiopharmaceuticals have restrained the occurrence of these incidents. The possibility of investigating this type of incidents by gamma and positron imaging is also quite limited. Additionally, a quick and precise analysis of radiochemical contamination is cumbersome and sometimes challenging if the spills of radioactive materials are low in activity. Herein, we report a case of accidental F-18 contamination in a service person during a routine cyclotron maintenance procedure. During target replacement, liquid F-18 was spilled on the person responsible for the maintenance. The activities of spills were immediately measured using contamination detectors, and the photon spectrum of contaminated clothes was assessed through gamma spectroscopy. Despite protective clothing, some skin areas were contaminated, which were then thoroughly washed. Later on, these areas were imaged, using positron emission tomography (PET), and a gamma camera (including spectroscopy). Two contaminated skin areas were located on the hand (9.7 and 14.7 cm2, respectively), which showed very low activities (19.0 and 22.8 kBq respectively at the time of incident). Based on the photon spectra, F-18 was confirmed as the main present radionuclide. PET imaging demonstrated the shape of these contaminated hot spots. However, the measured activities were very low due to the use of protective clothing. With prompt action and use of proper equipments at the time of incident, minimal radionuclide activities and their locations could be thoroughly analyzed. The cumulative skin doses of the contaminated regions were calculated at 1.52 and 2.00 mSv, respectively. In the follow-up, no skin changes were observed in the contaminated areas

Evaluation of Alpha-Therapy with Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer—the Role of Gamma Scintigraphy in Dosimetry and Pharmacokinetics

Radium-223-dichloride (223RaCl2) is a new bone-seeking calcium analogue alpha-emitter, which has obtained marketing authorization for the treatment skeletal metastases of hormone-refractory prostate cancer. The current treatment regimen is based on six consecutive doses of 223RaCl2 at 4 week intervals and the administered activity dose, 50 kBq/kg per cycle is based on patient weight. We analyzed two patients using quantitative serial gamma imaging to estimate dosimetry in tumors and see possible pharmacokinetic differences in the treatment cycles. The lesions were rather well visualized in gamma scintigraphy in spite of low gamma activity (&lt;1.1% gamma radiation) at 0, 7 and 28 days using 30–60 min acquisition times. Both our patients analyzed in serial gamma imagings, had two lesions in the gamma imaging field, the mean counts of the relative intensity varied from 27.8 to 36.5 (patient 1), and from 37.4 to 82.2 (patient 2). The half-lives varied from 1.8 days to 4.5 days during the six cycles (patient 1), and from 1.5 days to 3.6 days (patient 2), respectively. In the lesion half-lives calculated from the imaging the maximum difference between the treatment cycles in the same lesion was 2.0-fold (1.8 vs. 3.6). Of these patients, patient 1 demonstrated a serum PSA response, whereas there was no PSA response in patient 2. From our data, there were maximally up to 4.0-fold differences (62.1 vs. 246.6 ) between the relative absorbed radiation doses between patients as calculated from the quantitative standardized imaging to be delivered in only two lesions, and in the same lesion the maximum difference in the cycles was up to 2.3-fold (107.4 vs. 246.6). Our recommendation based on statistical simulation analysis, is serial measurement at days 0–8 at least 3 times, this improve the accuracy significantly to study the lesion activities, half-lives or calculated relative absorbed radiation doses as calculated from the imaging. Both our patients had originally two metastatic sites in the imaging field; the former patient demonstrated a serum PSA response and the latter demonstrated no PSA response. In these two patients there was no significant difference in the lesion activities, half-lives or calculated relative absorbed radiation doses as calculated from the quantitative imaging. Our results, although preliminary, suggest that dose monitoring can be included as a part of this treatment modality. On the other hand, from the absorbed radiation doses, the response cannot be predicted because with very similar doses, only the former patient responded

A Retrospective Comparative Study of Sodium Fluoride Na¹⁸F-PET/CT and ⁶⁸Ga-PSMA-11 PET/CT in the Bone Metastases of Prostate Cancer Using a Volumetric 3-D Radiomic Analysis

Bone is the most common metastatic site in prostate cancer (PCa). 68Ga-PSMA-11 (or gozetotide) and sodium fluoride-18 (Na18F) are rather new radiopharmaceuticals for assessing PCa-associated bone metastases. Gozetotide uptake reflects cell membrane enzyme activity and the sodium fluoride uptake measures bone mineralization in advanced PCa. Here, we aim to characterize this difference and possibly provide a new method for patient selection in targeted therapies. Methods: The study consisted of 14 patients with advanced PCa (M group > 5 lesions), who had had routine PET/CT both with PSMA and NaF over consecutive days, and 12 PCa patients with no skeletal metastases (N). The bone regions in CT were used to coregister the two PET/CT scans. The whole skeleton volume(s) of interest (VOIs) were defined using the CT component of PET (HU > 150); similarly, the sclerotic/dense bone was defined as HU > 600. Additional VOIs were defined for PET, with pathological threshold values for PSMA (SUV > 3.0) and NaF (SUV > 10). Besides the pathological bone volumes measured with each technique (CT, NaF, and PSMA-PET) and their contemporaneous combinations, overlapping VOIs with the CT-based skeletal and sclerotic volumes were also recorded. Additionally, thresholds of 4.0, 6.0, and 10.0 were tested for SUVPSMA. Results: In group M, the skeletal VOI volumes were 8.77 ± 1.80 L, and the sclerotic bone volumes were 1.32 ± 0.50 L; in contrast, in group N, they were 8.73 ± 1.43 L (skeletal) and 1.23 ± 0.28 L (sclerosis). The total enzyme activity for PSMA was 2.21 ± 5.15 in the M group and 0.078 ± 0.053 in the N group (p p p Conclusions: These results confirm our earlier findings that CT alone does not suit the evaluation of the extent of active skeletal metastases in PCa. PSMA and NaF images give complementary information about the extent of the active skeletal disease, which has a clinical impact and may change its management. The PSMA and NaF absolute volumes could be used for planning targeted therapies. A cut-off value 3.0 for SUVPSMA given here is the best correlation in the presentation of active metastatic skeletal disease

VMAT technique enables concomitant radiotherapy of prostate cancer and pelvic bone metastases

<div><p></p><p><b>Background.</b> Prostate cancer (PCa) patients with metastatic disease often suffer from skeletal pain and urinary retention impairing their quality of life. Prophylactic radiotherapy to bone metastases planned concomitantly with primary PCa radiotherapy could enable more precise control of combined dose in healthy tissues when compared to sequential palliative treatment.</p><p><b>Materials and methods.</b> Volumetric modulated arc therapy (VMAT) was planned for 14 PCa patients with primary bone metastases. The bone planning target volume (PTV_bone) was contoured together with the PTVs of prostate (pr), pelvic lymph nodes (ln) and seminal vesicles (sv). Another virtual plan was calculated excluding PTV_bone for dose volume histogram (DVH) comparison. DVHs were additionally compared to a set of actual VMAT treatment plans of a control cohort of 13 high risk PCa patients treated with PTV_pr, PTV_sv and PTV_ln. The prescribed doses varied between 42 and 76 Gy for PTV_bone.</p><p><b>Results.</b> Recommended healthy tissue tolerances (Quantec) were not exceeded except for one patient's rectum V_50Gy value. Rectum doses did not increase significantly due to the inclusion of PTV_bone. For bladder, there was a slight increase for V_65Gy and V_50Gy (2.7% and 7.4%). The DVHs of metastatic and non-metastatic patients were comparable. There were no differences in the PTV_pr DVH parameters, while mean PTV_ln dose increased by 3.7 Gy–4.4 Gy due to the increased treatment volume related to PTV_bone. All side effects were < grade 3 during the mean follow-up duration of 25 months.</p><p><b>Conclusions.</b> VMAT offers a good optimization tool for adding extra PTVs to the radiotherapy plan. Radiotherapy of bone metastases concomitantly with irradiation of the primary prostate tumor is a safe and well-tolerated approach and deserves to be studied in a randomized setting.</p></div