Research

10 pages, 511 KiB

Open AccessArticle

Predictors of PSMA PET Positivity: Analysis in a Selected Cohort of Biochemical Recurrence Prostate Cancer Patients after Radical Prostatectomy

by Paola Mapelli, Samuele Ghezzo, Cristiano Pini, Ana Maria Samanes Gajate, Alessandro Spataro, Carolina Bezzi, Claudio Landoni, Paola Scifo, Alberto Briganti, Arturo Chiti and Maria Picchio

Cancers 2023, 15(18), 4589; https://doi.org/10.3390/cancers15184589 - 15 Sep 2023

Viewed by 822

Abstract

Localized prostate cancer (PCa) can be treated with radical prostatectomy (RP). Up to 30% of patients undergoing this procedure experience biochemical recurrence (BCR), namely the rise in serum prostate-specific antigen (PSA) levels during the post-surgical follow-up, requiring further treatments and with the risk [...] Read more.

Localized prostate cancer (PCa) can be treated with radical prostatectomy (RP). Up to 30% of patients undergoing this procedure experience biochemical recurrence (BCR), namely the rise in serum prostate-specific antigen (PSA) levels during the post-surgical follow-up, requiring further treatments and with the risk of severe disease progression. Currently, the most accurate imaging technique to confirm, detect, and locate disease relapses in BCR patients is prostate-specific membrane antigen (PSMA)-targeted PET, as recommended by international clinical guidelines. The aim of the study was to investigate potential clinical and pathological predictors of PSMA PET positivity, validated by clinical and instrumental follow-up or histopathological data. In this study, a selected cohort of BCR patients after RP and no other PCa-related therapy who underwent either PSMA PET/CT or PSMA PET/MRI has been analysed. Among the considered predictors, both pathological staging after RP equal or higher than pT3a and higher PSA levels at the time of the scan were significantly correlated with PSMA PET positivity on multivariate logistic regression analysis. As expected, PSMA PET confirmed its role as an accurate imaging technique in the setting of BCR in PCa. These findings may inform appropriate and tailored patient selection and scan timing to optimize and fully exploit this powerful diagnostic tool. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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16 pages, 1368 KiB

Open AccessArticle

Comparison of Hormone-Sensitive Oligorecurrent Prostate Cancer Patients Based on Routine Use of Choline and/or PSMA PET/CT to Guide Metastasis-Directed Therapy

by Raphaël Metz, Aurore Rauscher, Loïg Vaugier, Stéphane Supiot, Franck Drouet, Loic Campion and Caroline Rousseau

Cancers 2023, 15(6), 1898; https://doi.org/10.3390/cancers15061898 - 22 Mar 2023

Cited by 2 | Viewed by 1728

Abstract

Background: In hormone-sensitive oligorecurrent prostate cancer (PC), the literature showed [68Ga]Ga-PSMA (PSMA) and [18F]F-choline (FCH) PET/CT can successfully guide metastasis-directed therapies (MDT). This observational retrospective study aimed to explore, in routine use, the impact of FCH or PSMA PET/CT in guiding MDT for [...] Read more.

Background: In hormone-sensitive oligorecurrent prostate cancer (PC), the literature showed [68Ga]Ga-PSMA (PSMA) and [18F]F-choline (FCH) PET/CT can successfully guide metastasis-directed therapies (MDT). This observational retrospective study aimed to explore, in routine use, the impact of FCH or PSMA PET/CT in guiding MDT for hormone-sensitive oligometastatic PC at different recurrences. Methods: In 2017–2020, patients initially treated with radical prostatectomy but, in biochemical recurrence (with PSA ≤ 2 ng/mL), diagnosed as oligometastatic based on FCH or PSMA PET/CT, were identified. MDT was stereotactic body radiotherapy (SBRT), elective nodal or prostate bed radiotherapy ± boost and ± androgen deprivation therapy (ADT). The primary endpoint was biochemical relapse-free survival (BR-FS), defined as a PSA increase ≥ 0.2 ng/mL above the nadir and increasing over two successive samples and the secondaries were ADT-free survival (ADT-FS). Results: 123 patients (70 PSMA and 53 FCH) were included. The median follow-up was 42.2 months. The median BR-FS was 24.7 months in the PSMA group versus 13.0 months in the FCH group (p = 0.008). Similarly, ADT-FS (p = 0.001) was longer in patients in the PSMA group. In multivariate analysis, a short PSA doubling time before imaging (p = 0.005) and MDT with SBRT (p = 0.001) were poor prognostic factors for BR-FS. Conclusions: Routine use of FCH or PSMA PET/CT in hormone-sensitive PC showed an advantage for using PSMA PET/CT to guide MDT in terms of BR-FS and ADT-FS in patients with low PSA value. Prospective studies are needed to confirm these hypotheses. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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14 pages, 1759 KiB

Open AccessArticle

A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis

by Rie von Eyben, Daniel S. Kapp, Manuela Andrea Hoffmann, Cigdem Soydal, Christian Uprimny, Irene Virgolini, Murat Tuncel, Mathieu Gauthé and Finn E. von Eyben

Cancers 2022, 14(21), 5461; https://doi.org/10.3390/cancers14215461 - 07 Nov 2022

Cited by 2 | Viewed by 1635 | Correction

Abstract

An individual patient meta-analysis followed 1216 patients with PSA-only recurrence (biochemical recurrence, BCR) restaged with [⁶⁸Ga]Ga-PSMA-11 PET/CT before the salvage treatment for median 3.5 years and analyzed the overall survival (OS). A new risk model included a good risk group with [...] Read more.

An individual patient meta-analysis followed 1216 patients with PSA-only recurrence (biochemical recurrence, BCR) restaged with [⁶⁸Ga]Ga-PSMA-11 PET/CT before the salvage treatment for median 3.5 years and analyzed the overall survival (OS). A new risk model included a good risk group with a prescan PSA < 0.5 ng/mL (26%), an intermediate risk group with a prescan PSA > 0.5 ng/mL and a PSMA PET/CT with 1 to 5 positive sites (65%), and a poor risk group with a prescan PSA > 0.5 ng/mL and a PSA PET/CT with > 5 positive sites (9%) (p < 0.0001, log rank test). The poor risk group had a five-year OS > 60%. Adding a BCR risk score by the European Association of Urology did not significantly improve the prediction of OS (p = 0.64). In conclusion, the restaging PSMA PET/CT markedly predicted the 5-year OS. The new risk model for patients with PSA-only relapse requires a restaging PSMA PET/CT for patients with a prescan PSA > 0.5 ng/mL and has a potential use in new trials aiming to improve the outcome for patients with PSA-only recurrence who have polysites prostate cancer detected on PSMA PET/CT. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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9 pages, 423 KiB

Open AccessArticle

Time after Synthesis and Time after Injection Do Not Affect Diagnostic Quality of [¹⁸F]F-PSMA 1007 PET

by Elisabeth Relt, Wolfgang Roll, Michael Claesener, Martin Bögemann, Matthias Weckesser and Kambiz Rahbar

Cancers 2022, 14(20), 5141; https://doi.org/10.3390/cancers14205141 - 20 Oct 2022

Cited by 1 | Viewed by 979

Abstract

PET imaging using PSMA ligands is increasingly used for staging in prostate cancer patients in different clinical indications. Unlike [⁶⁸Ga]Ga-labeled PSMA ligands, fluorinated compounds can be produced in large amounts; thus, they can be used for a higher number of patients. [...] Read more.

PET imaging using PSMA ligands is increasingly used for staging in prostate cancer patients in different clinical indications. Unlike [⁶⁸Ga]Ga-labeled PSMA ligands, fluorinated compounds can be produced in large amounts; thus, they can be used for a higher number of patients. One concern is that in patients studied a long time after synthesis (TaS) or time after injection (TaI), the specific activity may decline; thus, the signal may be lower in these patients. In this study, we investigated a potential effect of TaS and TaI on image quality. In total, 134 consecutive patients were included in this retrospective analysis on the effect of TaS and TaI on uptake in prostate cancer lesions. All the patients underwent [¹⁸F]F-PSMA-1007 PET-CT from 99 min up to 549 min after tracer quality control. TaS and TaI were compared to the quantitative tumoral uptake parameters SUVmax and SUVpeak. In a second exploratory part of the analysis, TaS and TaI were correlated to a physiological tracer uptake in different organs. TaS and TaI did not affect the SUVmax and SUVpeak in tumor lesions in [¹⁸F]F-PSMA-1007 PET. The physiological uptake in salivary glands, lacrimal glands and the ganglia, spleen and urine was not significantly correlated to TaS or TaI; in contrast to the mean liver uptake, showing a weak, but significant correlation to TaS. The [¹⁸F]F-PSMA-1007 uptake in prostate cancer lesions is not significantly dependent on the TaS and TaI. These results are extremely reassuring when performing [¹⁸F]F-PSMA-1007 PET a considerable time after synthesis. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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12 pages, 2489 KiB

Open AccessArticle

An Explorative Study of the Incidental High Renal Excretion of [¹⁸F]PSMA-1007 for Prostate Cancer PET/CT Imaging

by Youssra Allach, Amina Banda, Willemijn van Gemert, Michel de Groot, Yvonne Derks, Melline Schilham, Alexander Hoepping, Lars Perk, Martin Gotthardt, Marcel Janssen, James Nagarajah and Bastiaan M. Privé

Cancers 2022, 14(9), 2076; https://doi.org/10.3390/cancers14092076 - 21 Apr 2022

Cited by 2 | Viewed by 1944

Abstract

Positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) allows for accurate diagnosis and staging of prostate cancer (PCa). Compared to other PSMA PET tracers available, [¹⁸F]PSMA-1007 is predominantly excreted via the hepatobiliary tract resulting in low renal excretion which improves [...] Read more.

Positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) allows for accurate diagnosis and staging of prostate cancer (PCa). Compared to other PSMA PET tracers available, [¹⁸F]PSMA-1007 is predominantly excreted via the hepatobiliary tract resulting in low renal excretion which improves evaluation of the pelvic area. However, some patients do show high urinary uptake of [¹⁸F]PSMA-1007. The present study aimed to investigate this sudden high urinary uptake of [¹⁸F]PSMA-1007 by evaluating [¹⁸F]PSMA-1007 PET scans from PCa patients. In this single-center retrospective study, patients that underwent [¹⁸F]PSMA-1007 PET imaging between July 2018 and January 2021 were included. Data regarding the individual patient characteristics, scan acquisition and batch production were analyzed. To determine the urinary excretion of [¹⁸F]PSMA-1007, a region of interest was drawn in the bladder, and standardized uptake values (SUVs) were calculated and compared to SUVs in the prostate. An SUVmax of >10 was considered high urinary excretion, an SUVmax 7.5–10 intermediate and an SUVmax < 7.5 low urinary excretion. A total of 344 patients underwent [¹⁸F]PSMA-1007 PET/CT imaging, with 37 patients receiving three or more [¹⁸F]PSMA-1007 PET/CT scans. The mean SUVmean and SUVmax of the bladder were 3.9 (SD 2.9) and 5.9 (SD 4.2), respectively. Fourteen percent of patients showed high urinary uptake of [¹⁸F]PSMA-1007. Twelve of the thirty-seven patients (32.4%) that had multiple scans showed a varying urinary uptake of [¹⁸F]PSMA-1007 per PSMA PET/CT scan. In terms of patient characteristics, risk factors, medication and blood laboratory results, no significant influencing variables were found. Nor was there a difference observed in the batch size and the mean radiochemical purity of PSMA-1007 for high- and low-excreting patients. However, the bladder volume affected the mean SUVmax in the bladder significantly, with higher SUVs in lower bladder volumes. In this study, we observed that a higher SUV in the urinary tract seemed to occur in patients with low bladder volume. A prospective study is needed to corroborate this hypothesis. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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11 pages, 1211 KiB

Open AccessArticle

Safety and Efficacy of ¹⁷⁷Lutetium-PSMA-617 Radioligand Therapy Shortly after Failing ²²³Radium-Dichloride

by Justus Baumgarten, Daniel Groener, Christina Nguyen Ngoc, Nicolai Mader, Maximilian Chaurasia, Karen Davis, Jennifer Wichert, Felix K. H. Chun, Nikolaos Tselis, Christian Happel, Frank Grünwald and Amir Sabet

Cancers 2022, 14(3), 557; https://doi.org/10.3390/cancers14030557 - 22 Jan 2022

Cited by 8 | Viewed by 3703

Abstract

Bone-seeking ²²³Radium-dichloride (²²³Ra) is an established treatment prolonging survival and reducing morbidity in selected patients with metastatic castration-resistant prostate cancer (mCRPC) with skeletal involvement. Radioligand therapy with ¹⁷⁷Lutetium-PSMA-617 (¹⁷⁷Lu-PSMA-617) has been increasingly implemented in patients with mCRPC [...] Read more.

Bone-seeking ²²³Radium-dichloride (²²³Ra) is an established treatment prolonging survival and reducing morbidity in selected patients with metastatic castration-resistant prostate cancer (mCRPC) with skeletal involvement. Radioligand therapy with ¹⁷⁷Lutetium-PSMA-617 (¹⁷⁷Lu-PSMA-617) has been increasingly implemented in patients with mCRPC failing conventional treatment options. In this study, the safety and efficacy of ¹⁷⁷Lu-PSMA-617 in patients with progressive bone involvement under treatment with ²²³Ra was assessed. Twenty-eight men (median age 73 years, range 63–89 years) with progressive mCRPC, who started ¹⁷⁷Lu-PSMA-617 within 8 weeks after the last ²²³Ra administration, received a median of 4 (IQR 3–6) and a total of 120 cycles of ²²³Ra and a median of 4 (IQR 2–7) cycles ¹⁷⁷Lu-PSMA-617 with a mean treatment activity of 6.5 ± 1.2 GBq per cycle, reaching a mean cumulative activity of 30.7 ± 23.4 GBq. A PSA response (≥50% PSA decline 12 weeks after the first ¹⁷⁷Lu-PSMA-617 cycle) was observed in 18/28 (64.3%) patients and imaging-based partial remission (PR) was observed in 11/28 (39.3%) patients. Median imaging-based progression-free survival (PFS) was 10 (95% CI, 6–14) months and median overall survival (OS) was 18 (95% CI, 14–22) months. Patients with low bone tumor burden (2–20 lesions) had a significantly longer OS (28 vs. 14 months, p < 0.045) compared to patients with a high tumor burden (>20 lesions). Grade ≥ 3 hematological toxicity was observed in six patients after their last treatment cycle with anemia, leukopenia and thrombocytopenia in 5/28 (17.9%), 4/28 (14.3%) and 6/28 (21.4%) patients, respectively. In progressive bone-metastatic mCRPC patients, prompt initiation of ¹⁷⁷Lu-PSMA-617 after failing ²²³Ra is effective with an acceptable toxicity profile. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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11 pages, 1649 KiB

Open AccessArticle

Outcome of ¹⁷⁷Lu-PSMA-617 Radioligand Therapy in Chemo-Refractory Patients with Metastatic Castration-Resistant Early-Onset Prostate Cancer

by Nicolai Mader, Daniel Groener, Nikolaos Tselis, Séverine Banek, James Nagarajah, Frank Grünwald and Amir Sabet

Cancers 2021, 13(16), 4193; https://doi.org/10.3390/cancers13164193 - 20 Aug 2021

Cited by 5 | Viewed by 2756

Abstract

The aim of this retrospective study was to assess the outcome of patients with metastasized castration-resistant early-onset prostate cancer refractory to chemotherapy receiving radioligand therapy with ¹⁷⁷Lutetium-PSMA-617 (LuPSMA-RLT). Twenty-five patients of ≤55 years of age at prostate cancer diagnosis, treated with a [...] Read more.

The aim of this retrospective study was to assess the outcome of patients with metastasized castration-resistant early-onset prostate cancer refractory to chemotherapy receiving radioligand therapy with ¹⁷⁷Lutetium-PSMA-617 (LuPSMA-RLT). Twenty-five patients of ≤55 years of age at prostate cancer diagnosis, treated with a median of four (IQR 2–6) cycles (mean of 7.7 ± 1.4 GBq per cycle) every 6–8 weeks, were analyzed. Survival outcome was calculated based on the Kaplan–Meier method. The median progression-free survival (PFS) was 3.8 months (95% CI 2.3–5.3), and overall survival (OS) was 8.5 months (95% CI 6.2–10.8). An initial PSA reduction (≥ 50%) was observed in 9/25 (36%) of patients without being significantly associated with OS (p = 0.601). PSA response (PSA decline ≥50% at 12 weeks) was observed in 12/25 (48%) of patients and significantly associated with longer OS (16.0 months, 95% CI 7.4–24.6 vs. 4.0 months, 95% CI 1.1–6.9, p = 0.002). Imaging-based response using ⁶⁸Ga-PSMA-11-PET/CT after two to three cycles was seen in 11/25 (44%). Additionally, responders had a significantly longer median PFS (8.7 months, 95% CI 1.3–16.1 vs. 1.9 months, 95% CI 1.7–2.2, p < 0.001) and OS (16.0 months, 95% CI 7.6–24.4 vs. 4.0 months, 95% CI 0.9–7.1; p = 0.002). Intra- or post-therapeutic toxicity was graded according to the CTCAE v5.0 criteria. Newly developing grade ≥ 3 anemia, leukopenia, and thrombocytopenia occurred in three (12%), one (4%), and three (12%) patients, respectively. One patient showed renal toxicity (grade ≥ 3) during follow-up. Pain palliation (>2 level VAS decline) was achieved in 9/14 (64%) and performance status improvement (ECOG level decline ≥ 1) in 8/17 (47%) of patients. Compared to previous reports, radioligand therapy with ¹⁷⁷Lu-PSMA-617 in metastasized castration-resistant early-onset prostate cancer patients refractory to chemotherapy yields similar response rates with a comparable safety profile, but is associated with shorter survival. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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15 pages, 1311 KiB

Open AccessArticle

Salvage Radioligand Therapy with Repeated Cycles of ¹⁷⁷Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer with Diffuse Bone Marrow Involvement

by Daniel Groener, Justus Baumgarten, Sebastian Haefele, Christian Happel, Konrad Klimek, Nicolai Mader, Christina Nguyen Ngoc, Nikolaos Tselis, Felix K. H. Chun, Frank Grünwald and Amir Sabet

Cancers 2021, 13(16), 4017; https://doi.org/10.3390/cancers13164017 - 10 Aug 2021

Cited by 5 | Viewed by 3523

Abstract

Advanced stage metastatic prostate cancer with extensive bone marrow involvement is associated with a high risk of therapy-induced myelotoxicity and unfavorable outcomes. The role of salvage radioligand therapy (RLT) with ¹⁷⁷Lu-PSMA-617 in this subset of patients remains to be further elucidated. Forty-five [...] Read more.

Advanced stage metastatic prostate cancer with extensive bone marrow involvement is associated with a high risk of therapy-induced myelotoxicity and unfavorable outcomes. The role of salvage radioligand therapy (RLT) with ¹⁷⁷Lu-PSMA-617 in this subset of patients remains to be further elucidated. Forty-five patients with progressive metastatic castration-resistant prostate cancer (mCRPC) and diffuse bone marrow involvement were treated with repeated cycles of RLT after having exhausted standard treatment options. A mean treatment activity of 7.4 ± 1.4 GBq ¹⁷⁷Lu-PSMA-617 was administered in a median of four treatment cycles (IQR 2-6) and the mean cumulative activity was 32.6 ± 20.1 GBq. After two RLT cycles, ≥50% PSA decline was observed in 25/45 (56%) patients and imaging-based partial remission (PR) was observed in 18/45 (40%) patients. Median imaging-based progression-free survival (PFS) was 6.4 mo (95% CI, 3.0–9.8) and the median overall survival (OS) was 10.2 months (95% CI, 7.2–12.8). The biochemical response translated into a significantly prolonged PFS (12.9 vs. 2.8 mo, p < 0.001) and OS (13.5 vs. 6.7 mo, p < 0.001). Patients with PR on interim imaging after two cycles had a longer median OS compared to patients with stable or progressive disease (15.5 vs. 7.1 mo, p < 0.001). Previous taxane-based chemotherapy (HR 3.21, 95%CI 1.18–8.70, p = 0.02) and baseline LDH levels (HR 1.001, 95%CI 1.000–1.001, p = 0.04) were inversely associated with OS on a Cox-regression analysis. Grade ≥ 3 hematological decline was observed after 22/201 (11%) cycles with anemia, leukopenia and thrombocytopenia in 15/45 (33%), 6/45 (13%) and 8/45 (18%) patients, respectively. Cumulative treatment activity and absorbed whole-body dose were not correlated with new onset grade ≥ 3 hematotoxicity (p = 0.91, p = 0.69). No event of grade ≥ 3 chronic kidney disease was observed during RLT or the follow-up. Last line RLT with ¹⁷⁷Lu-PSMA-617 in mCRPC patients with diffuse bone marrow involvement may thus contribute to prolonged disease control at an acceptable safety profile. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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24 pages, 8214 KiB

Open AccessArticle

Comparison of Quantification of Target-Specific Accumulation of [¹⁸F]F-siPSMA-14 in the HET-CAM Model and in Mice Using PET/MRI

by Jessica Löffler, Carmen Hamp, Ellen Scheidhauer, Daniel Di Carlo, Christoph Solbach, Alireza Abaei, Li Hao, Gerhard Glatting, Ambros J. Beer, Volker Rasche and Gordon Winter

Cancers 2021, 13(16), 4007; https://doi.org/10.3390/cancers13164007 - 09 Aug 2021

Cited by 9 | Viewed by 2823

Abstract

Assessment of biodistribution and specific tumor accumulation is essential for the development of new radiopharmaceuticals and requires animal experiments. The HET-CAM (hens-egg test—chorioallantoic membrane) model can be used in combination with the non-invasive imaging modalities PET and MRI for pre-selection during radiopharmaceutical development [...] Read more.

Assessment of biodistribution and specific tumor accumulation is essential for the development of new radiopharmaceuticals and requires animal experiments. The HET-CAM (hens-egg test—chorioallantoic membrane) model can be used in combination with the non-invasive imaging modalities PET and MRI for pre-selection during radiopharmaceutical development to reduce the number of animal experiments required. Critical to the acceptance of this model is the demonstration of the quantifiability and reproducibility of these data compared to the standard animal model. Tumor accumulation and biodistribution of the PSMA-specific radiotracer [¹⁸F]F-siPSMA-14 was analyzed in the chick embryo and in an immunodeficient mouse model. Evaluation was based on MRI and PET data in both models. γ-counter measurements and histopathological analyses complemented these data. PSMA-specific accumulation of [¹⁸F]F-siPSMA-14 was successfully demonstrated in the HET-CAM model, similar to the results obtained by mouse model studies. The combination of MR and PET imaging allowed precise quantification of peptide accumulation, initial assessment of biodistribution, and accurate determination of tumor volume. Thus, the use of the HET-CAM model is suitable for the pre-selection of new radiopharmaceuticals and potentially reduces animal testing in line with the 3Rs principles of animal welfare. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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18 pages, 2850 KiB

Open AccessArticle

Streamlined Schemes for Dosimetry of ¹⁷⁷Lu-Labeled PSMA Targeting Radioligands in Therapy of Prostate Cancer

by Jens Kurth, Martin Heuschkel, Alexander Tonn, Anna Schildt, Oliver W. Hakenberg, Bernd J. Krause and Sarah M. Schwarzenböck

Cancers 2021, 13(15), 3884; https://doi.org/10.3390/cancers13153884 - 01 Aug 2021

Cited by 12 | Viewed by 2650

Abstract

(Background) Aim of this retrospective analysis was to investigate in mCRPC patients treated with [¹⁷⁷Lu]Lu-PSMA-617 whether the absorbed dose (AD) in organs at risk (OAR, i.e., kidneys and parotid glands) can be calculated using simplified methodologies with sufficient accuracy. For this [...] Read more.

(Background) Aim of this retrospective analysis was to investigate in mCRPC patients treated with [¹⁷⁷Lu]Lu-PSMA-617 whether the absorbed dose (AD) in organs at risk (OAR, i.e., kidneys and parotid glands) can be calculated using simplified methodologies with sufficient accuracy. For this calculation, results and kinetics of the first therapy cycle were used. (Methods) 46 patients treated with 2 to 6 cycles of [¹⁷⁷Lu]Lu-PSMA-617 were included. As reference (current clinical standard) full dosimetry of the OAR based on quantitative imaging (whole body scintigraphy and quantitative SPECT/CT at 2, 24, 48 and 72 h p.i.) for every cycle was used. Alternatively, two dosimetry schemes, simplified in terms of image acquisition and dose calculation, were established, both assuming nearly unchanged kinetics of the radiopharmaceutical for subsequent cycles. (Results) In general, for both OAR the simplified methods provided results that were consistent with the dosimetric reference method, both per cycle and in terms of cumulative AD. Best results were obtained when imaging was performed at 48 h p.i. in each of the subsequent cycles. However, both simplified methods tended to underestimate the cumulative AD. (Conclusion) Simplified dosimetry schemes are feasible to tailor multi-cycle [¹⁷⁷Lu]Lu-PSMA-targeted therapies. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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11 pages, 1742 KiB

Open AccessArticle

Evaluation of ⁶⁸Ga-PSMA-11 PET-MRI in Patients with Advanced Prostate Cancer Receiving ¹⁷⁷Lu-PSMA-617 Therapy: A Radiomics Analysis

by Wolfgang Roll, Philipp Schindler, Max Masthoff, Robert Seifert, Katrin Schlack, Martin Bögemann, Lars Stegger, Matthias Weckesser and Kambiz Rahbar

Cancers 2021, 13(15), 3849; https://doi.org/10.3390/cancers13153849 - 30 Jul 2021

Cited by 15 | Viewed by 2236

Abstract

¹⁷⁷Lutetium PSMA-617 (Lu-PSMA) therapy in patients with metastatic castration resistant prostate cancer (mCRPC) has gained visibility through the ongoing phase III trial. The data on prediction of therapy outcome and survival out of pretherapeutic imaging parameters is still sparse. In this study, [...] Read more.

¹⁷⁷Lutetium PSMA-617 (Lu-PSMA) therapy in patients with metastatic castration resistant prostate cancer (mCRPC) has gained visibility through the ongoing phase III trial. The data on prediction of therapy outcome and survival out of pretherapeutic imaging parameters is still sparse. In this study, the predictive and prognostic value of radiomic features from ⁶⁸Ga-PSMA-11 PET-MRI are analyzed. In total, 21 patients with mCRPC underwent ⁶⁸Ga-PSMA-11 PET-MRI before Lu-PSMA therapy. The PET-positive tumor volume was defined and transferred to whole-body T2-, T1- and contrast-enhanced T1-weighted MRI-sequences. The radiomic features from PET and MRI sequences were extracted by using a freely available software package. For selecting features that allow differentiation of biochemical response (PSA decrease > 50%), a stepwise dimension reduction was performed. Logistic regression models were fitted, and selected features were tested for their prognostic value (overall survival) in all patients. Eight patients achieved biochemical response after Lu-PSMA therapy. Ten independent radiomic features differentiated well between responders and non-responders. The logistic regression model, including the feature interquartile range from T2-weighted images, revealed the highest accuracy (AUC = 0.83) for the prediction of biochemical response after Lu-PSMA therapy. Within the final model, patients with a biochemical response (p = 0.003) and higher T2 interquartile range values in pre-therapeutic imaging (p = 0.038) survived significantly longer. This proof-of-concept study provides first evidence on a potential predictive and prognostic value of radiomic analysis of pretherapeutic ⁶⁸Ga-PSMA-11 PET-MRI before Lu-PSMA therapy. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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19 pages, 2454 KiB

Open AccessArticle

Towards Targeted Alpha Therapy with Actinium-225: Chelators for Mild Condition Radiolabeling and Targeting PSMA—A Proof of Concept Study

by Falco Reissig, David Bauer, Kristof Zarschler, Zbynek Novy, Katerina Bendova, Marie-Charlotte Ludik, Klaus Kopka, Hans-Jürgen Pietzsch, Milos Petrik and Constantin Mamat

Cancers 2021, 13(8), 1974; https://doi.org/10.3390/cancers13081974 - 20 Apr 2021

Cited by 26 | Viewed by 6196

Abstract

Currently, targeted alpha therapy is one of the most investigated topics in radiopharmaceutical cancer management. Especially, the alpha emitter ²²⁵Ac has excellent nuclear properties and is gaining increasing popularity for the treatment of various tumor entities. We herein report on the synthesis [...] Read more.

Currently, targeted alpha therapy is one of the most investigated topics in radiopharmaceutical cancer management. Especially, the alpha emitter ²²⁵Ac has excellent nuclear properties and is gaining increasing popularity for the treatment of various tumor entities. We herein report on the synthesis of two universal ²²⁵Ac-chelators for mild condition radiolabeling and binding to conjugate molecules of pharmacological interest via the copper-mediated click chemistry. A convenient radiolabeling procedure was investigated as well as the complex stability proved for both chelators and two PSMA (prostate-specific membrane antigen)-targeting model radioconjugates. Studies regarding affinity and cell survival were performed on LNCaP cells followed by biodistribution studies, which were performed using LNCaP tumor-bearing mice. High efficiency radiolabeling for all conjugates was demonstrated. Cell binding studies revealed a fourfold lower cell affinity for the PSMA radioconjugate with one targeting motif compared to the radioconjugate owing two targeting motifs. Additionally, these differences were verified by in vitro cell survival evaluation and biodistribution studies, both showing a higher cell killing efficiency for the same dose, a higher tumor uptake (15%ID/g) and a rapid whole body clearance after 24 h. The synthesized chelators will overcome obstacles of lacking stability and worse labeling needs regarding ²²⁵Ac complexation using the DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid) chelator. Moreover, the universal functionalization expands the coverage of these chelators in combination with any sensitive bio(macro)molecule, thus improving treatment of any addressable tumor target. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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13 pages, 1413 KiB

Open AccessArticle

Correlation between Intraprostatic PSMA Uptake and MRI PI-RADS of [⁶⁸Ga]Ga-PSMA-11 PET/MRI in Patients with Prostate Cancer: Comparison of PI-RADS Version 2.0 and PI-RADS Version 2.1

by Jing Zhao, Dilyana B. Mangarova, Julia Brangsch, Avan Kader, Bernd Hamm, Winfried Brenner and Marcus R. Makowski

Cancers 2020, 12(12), 3523; https://doi.org/10.3390/cancers12123523 - 26 Nov 2020

Cited by 11 | Viewed by 2306

Abstract

Purpose: We aimed to evaluate the correlation between PSMA uptake and magnetic resonance imaging (MRI) PI-RADS of simultaneous [⁶⁸Ga]Ga-PSMA-11 PET/MRI regarding PI-RADS version 2.0 and 2.1 respectively and compared the difference between these two versions. Materials and Methods: We retrospectively analyzed [...] Read more.

Purpose: We aimed to evaluate the correlation between PSMA uptake and magnetic resonance imaging (MRI) PI-RADS of simultaneous [⁶⁸Ga]Ga-PSMA-11 PET/MRI regarding PI-RADS version 2.0 and 2.1 respectively and compared the difference between these two versions. Materials and Methods: We retrospectively analyzed a total of forty-six patients with biopsy-proven prostate cancer who underwent simultaneous [⁶⁸Ga]Ga-PSMA-11 PET/MRI. We classified the lesions regarding PI-RADS version 2.0 and 2.1, peripheral zone (PZ), and transitional zone (TZ), respectively. Based on regions of interest (ROI), standardized uptake values maximum (SUVmax), and corresponding lesion-to-background ratios (LBR) of SUVmax of each category, PI-RADS score 1 to 5, were measured. A comparison between PI-RADS version 2.0 and PI-RADS version 2.1 was performed. Results: A total of 215 focal prostate lesions were analyzed, including two subgroups, 125 TZ and 90 PZ. Data are reported as median and interquartile range (IQR). Regarding PI-RADS version 2.1, TZ SUVmax of each category were 1.5 (0.5, 1.9), 1.9 (0.8, 2.3), 3.3 (2.1, 4.6), 4.2 (3.1, 5.7), 7.3 (5.2, 9.7). PZ SUVmax of each category were 1.0 (0.8, 1.6), 2.5 (1.5, 3.2), 3.3 (1.9, 4.5), 4.3 (3.0, 5.4), 7.4 (5.0, 9.3). Regarding the inter-reader agreement of the overall PI-RADS assessment category, the kappa value was 0.723 for version 2.0 and 0.853 for version 2.1. Conclusion: Revisions of PI-RADS version 2.1 results in variations in lesions classification. Lesions with the PI-RADS category of 3, 4, and 5 present relatively higher intraprostatic PSMA uptake, while lesions with the PI-RADS category of 1 and 2 present relatively lower and similar uptake. Version 2.1 has higher inter-reader reproducibility than version 2.0. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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30 pages, 1511 KiB

Open AccessFeature PaperReview

PSMA-Targeting Radiopharmaceuticals for Prostate Cancer Therapy: Recent Developments and Future Perspectives

by Mohamed El Fakiri, Nicolas M. Geis, Nawal Ayada, Matthias Eder and Ann-Christin Eder

Cancers 2021, 13(16), 3967; https://doi.org/10.3390/cancers13163967 - 05 Aug 2021

Cited by 22 | Viewed by 5948

Abstract

Prostate cancer (PC) is the second most common cancer among men, with 1.3 million yearly cases worldwide. Among those cancer-afflicted men, 30% will develop metastases and some will progress into metastatic castration-resistant prostate cancer (mCRPC), which is associated with a poor prognosis and [...] Read more.

Prostate cancer (PC) is the second most common cancer among men, with 1.3 million yearly cases worldwide. Among those cancer-afflicted men, 30% will develop metastases and some will progress into metastatic castration-resistant prostate cancer (mCRPC), which is associated with a poor prognosis and median survival time that ranges from nine to 13 months. Nevertheless, the discovery of prostate specific membrane antigen (PSMA), a marker overexpressed in the majority of prostatic cancerous tissue, revolutionised PC care. Ever since, PSMA-targeted radionuclide therapy has gained remarkable international visibility in translational oncology. Furthermore, on first clinical application, it has shown significant influence on therapeutic management and patient care in metastatic and hormone-refractory prostate cancer, a disease that previously had remained immedicable. In this article, we provide a general overview of the main milestones in the development of ligands for PSMA-targeted radionuclide therapy, ranging from the firstly developed monoclonal antibodies to the current state-of-the-art low molecular weight entities conjugated with various radionuclides, as well as potential future efforts related to PSMA-targeted radionuclide therapy. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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20 pages, 1478 KiB

Open AccessReview

Evolving Castration Resistance and Prostate Specific Membrane Antigen Expression: Implications for Patient Management

by Katharina Kessel, Christof Bernemann, Martin Bögemann and Kambiz Rahbar

Cancers 2021, 13(14), 3556; https://doi.org/10.3390/cancers13143556 - 16 Jul 2021

Cited by 9 | Viewed by 3799

Abstract

Metastatic castration-resistant prostate cancer (mCRPC) remains an incurable disease, despite multiple novel treatment options. The role of prostate-specific membrane antigen (PSMA) in the process of mCRPC development has long been underestimated. During the last years, a new understanding of the underlying molecular mechanisms [...] Read more.

Metastatic castration-resistant prostate cancer (mCRPC) remains an incurable disease, despite multiple novel treatment options. The role of prostate-specific membrane antigen (PSMA) in the process of mCRPC development has long been underestimated. During the last years, a new understanding of the underlying molecular mechanisms of rising PSMA expression and its association with disease progression has emerged. Accurate understanding of these complex interactions is indispensable for a precise diagnostic process and ultimately successful treatment of advanced prostate cancer. The combination of different novel therapeutics such as androgen deprivation agents, 177LU-PSMA radioligand therapy and PARP inhibitors promises a new kind of efficacy. In this review, we summarize the current knowledge about the most relevant molecular mechanisms around PSMA in mCRPC development and how they can be implemented in mCRPC management. Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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1 pages, 418 KiB

Open AccessCorrection

Correction: von Eyben et al. A Risk Model for Patients with PSA-Only Recurrence (Biochemical Recurrence) Based on PSA and PSMA PET/CT: An Individual Patient Data Meta-Analysis. Cancers 2022, 14, 5461

by Rie von Eyben, Daniel S. Kapp, Manuela Andrea Hoffmann, Cigdem Soydal, Christian Uprimny, Irene Virgolini, Murat Tuncel, Mathieu Gauthé and Finn E. von Eyben

Cancers 2023, 15(4), 1035; https://doi.org/10.3390/cancers15041035 - 07 Feb 2023

Cited by 1 | Viewed by 750

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Prostate-Specific Membrane Antigen (PSMA))

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