Research

20 pages, 7272 KiB

Open AccessArticle

Preliminary Results of an Ongoing Prospective Clinical Trial on the Use of ⁶⁸Ga-PSMA and ⁶⁸Ga-DOTA-RM2 PET/MRI in Staging of High-Risk Prostate Cancer Patients

by Paola Mapelli, Samuele Ghezzo, Ana Maria Samanes Gajate, Erik Preza, Giorgio Brembilla, Vito Cucchiara, Naghia Ahmed, Carolina Bezzi, Luca Presotto, Valentino Bettinardi, Annarita Savi, Patrizia Magnani, Raffaele Menichini, Angela Coliva, Ilaria Neri, Ettore Di Gaeta, Luigi Gianolli, Massimo Freschi, Alberto Briganti, Francesco De Cobelli, Paola Scifo and Maria Picchio Show full author list Hide full author list

Diagnostics 2021, 11(11), 2068; https://doi.org/10.3390/diagnostics11112068 - 09 Nov 2021

Cited by 18 | Viewed by 1988

Abstract

The aim of the present study is to investigate the synergic role of ⁶⁸Ga-PSMA PET/MRI and ⁶⁸Ga-DOTA-RM2 PET/MRI in prostate cancer (PCa) staging. We present pilot data on twenty-two patients with biopsy-proven PCa that underwent ⁶⁸Ga-PSMA PET/MRI for staging purposes, [...] Read more.

The aim of the present study is to investigate the synergic role of ⁶⁸Ga-PSMA PET/MRI and ⁶⁸Ga-DOTA-RM2 PET/MRI in prostate cancer (PCa) staging. We present pilot data on twenty-two patients with biopsy-proven PCa that underwent ⁶⁸Ga-PSMA PET/MRI for staging purposes, with 19/22 also undergoing ⁶⁸Gaa-DOTA-RM2 PET/MRI. TNM classification based on image findings was performed and quantitative imaging parameters were collected for each scan. Furthermore, twelve patients underwent radical prostatectomy with the availability of histological data that were used as the gold standard to validate intraprostatic findings. A DICE score between regions of interest manually segmented on the primary tumour on ⁶⁸Ga-PSMA PET, ⁶⁸Ga-DOTA-RM2 PET and on T2 MRI was computed. All imaging modalities detected the primary PCa in 18/19 patients, with ⁶⁸Ga-DOTA-RM2 PET not detecting any lesion in 1/19 patients. In the remaining patients, ⁶⁸Ga-PSMA and MRI were concordant. Seven patients presented seminal vesicles involvement on MRI, with two of these being also detected by ⁶⁸Ga-PSMA, and ⁶⁸Ga-DOTA-RM2 PET being negative. Regarding extraprostatic disease, ⁶⁸Ga-PSMA PET, ⁶⁸Ga-DOTA-RM2 PET and MRI resulted positive in seven, four and five patients at lymph-nodal level, respectively, and at a bone level in three, zero and one patients, respectively. These preliminary results suggest the potential complementary role of ⁶⁸Ga-PSMA PET, ⁶⁸Ga-DOTA-RM2 PET and MRI in PCa characterization during the staging phase. Full article

(This article belongs to the Special Issue PSMA in Prostate Cancer)

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10 pages, 403 KiB

Open AccessArticle

Comparison of Early Imaging and Imaging 60 min Post-Injection after Forced Diuresis with Furosemide in the Assessment of Local Recurrence in Prostate Cancer Patients with Biochemical Recurrence Referred for 68Ga-PSMA-11 PET/CT

by Steffen Bayerschmidt, Christian Uprimny, Alexander Stephan Kroiss, Josef Fritz, Bernhard Nilica, Hanna Svirydenka, Clemens Decristoforo, Elisabeth von Guggenberg, Wolfgang Horninger and Irene Johanna Virgolini

Diagnostics 2021, 11(7), 1191; https://doi.org/10.3390/diagnostics11071191 - 30 Jun 2021

Cited by 6 | Viewed by 1837

Abstract

Background: 68Ga-PSMA-11 PET/CT is a promising method for the assessment of local recurrence (LR) in prostate cancer (PCa) patients. The aim of this study was to evaluate the diagnostic performance of early 68Ga-PSMA-11 PET imaging in comparison to 68Ga-PSMA-11 PET imaging 60 min [...] Read more.

Background: 68Ga-PSMA-11 PET/CT is a promising method for the assessment of local recurrence (LR) in prostate cancer (PCa) patients. The aim of this study was to evaluate the diagnostic performance of early 68Ga-PSMA-11 PET imaging in comparison to 68Ga-PSMA-11 PET imaging 60 min post-injection (p.i.) in the detection of LR in patients with biochemical recurrence (BR) of prostate carcinoma. Materials and Methods: 190 image sets of patients with BR in PCa who underwent 68Ga-PSMA-11 PET/CT were assessed retrospectively (median prostate specific antigen (PSA) value, 0.70 ng/mL (range, 0.1–105.6 ng/mL)). Patients received an early static scan of the pelvic area (median, 248 s p.i. (range, 56–923 s)) and a whole-body scan 60 min p.i. (median, 64 min p.i. (range, 45–100 min)) with intravenous administration of 20 mg furosemide i.v. at the time of tracer application, followed by intravenous hydration with 500 mL of sodium chloride (NaCl 0.9%). Assessment was based on visual analysis and calculation of the maximum standardized uptake value (SUVmax) of the pathologic lesions present in the prostate fossa found in the early PET imaging and 60 min PET scans. The scans were characterized as negative, positive, or equivocal. The results were compared, and the combination of early and 60 min p.i. imaging was evaluated. Results: Image assessment resulted in 30 (15.8%) positive, 17 (8.9%) equivocal, and 143 (75.3%) negative findings in early scans, and 28 (14.7%) positive, 25 (13.2%) equivocal, and 137 (72.1%) negative findings of LR in 60 min p.i. images. For combined image analysis, 33 (17.4%) cases were positive and 20 (10.5%) were equivocal. There was no statistical significance between the number of positive (p = 0.815), negative (p = 0.327), and equivocal (p = 0.152) findings. Furthermore, the combination of both scans showed no statistically significant differences for the positive and negative findings (p = 0.063). The median SUVmax was 4.9 (range, 2.0–55.2) for positive lesions in the early scans and 8.0 (range, 2.1–139.9) in the scans 60 min p.i. The median SUVmax for bladder activity was 2.5 (range, 0.9–12.2) in the early scans and 8.2 (range, 1.8–27.6) in the scans 60 min p.i. Conclusion: Early static imaging additional to 68Ga-PSMA-11 PET images acquired 60 min p.i. has limited value in patients prepared with furosemide and hydration, and showed no statistically significant change in the detection rate (DR) of LR and the number of equivocal findings. Based on our results, in departments following a protocol with forced diuresis, including furosemide, additional early static imaging cannot be routinely recommended for the assessment of BR in PCa patients. Full article

(This article belongs to the Special Issue PSMA in Prostate Cancer)

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10 pages, 10392 KiB

Open AccessArticle

Comparison of Regularized Reconstruction and Ordered Subset Expectation Maximization Reconstruction in the Diagnostics of Prostate Cancer Using Digital Time-of-Flight ⁶⁸Ga-PSMA-11 PET/CT Imaging

by Olof Jonmarker, Rimma Axelsson, Ted Nilsson and Stefan Gabrielson

Diagnostics 2021, 11(4), 630; https://doi.org/10.3390/diagnostics11040630 - 31 Mar 2021

Cited by 6 | Viewed by 1780

Abstract

In prostate cancer, the early detection of distant spread has been shown to be of importance. Prostate-specific membrane antigen (PSMA)-binding radionuclides in positron emission tomography (PET) is a promising method for precise disease staging. PET diagnostics depend on image reconstruction techniques, and ordered [...] Read more.

In prostate cancer, the early detection of distant spread has been shown to be of importance. Prostate-specific membrane antigen (PSMA)-binding radionuclides in positron emission tomography (PET) is a promising method for precise disease staging. PET diagnostics depend on image reconstruction techniques, and ordered subset expectation maximization (OSEM) is the established standard. Block sequential regularized expectation maximization (BSREM) is a more recent reconstruction algorithm and may produce fewer equivocal findings and better lesion detection. Methods: ⁶⁸Ga PSMA-11 PET/CT scans of patients with de novo or suspected recurrent prostate cancer were retrospectively reformatted using both the OSEM and BSREM algorithms. The lesions were counted and categorized by three radiologists. The intra-class correlation (ICC) and Cohen’s kappa for the inter-rater reliability were calculated. Results: Sixty-one patients were reviewed. BSREM identified slightly fewer lesions overall and fewer equivocal findings. ICC was excellent with regards to definitive lymph nodes and bone metastasis identification and poor with regards to equivocal metastasis irrespective of the reconstruction algorithm. The median Cohen’s kappa were 0.66, 0.74, 0.61 and 0.43 for OSEM and 0.61, 0.63, 0.66 and 0.53 for BSREM, with respect to the tumor, local lymph nodes, metastatic lymph nodes and bone metastasis detection, respectively. Conclusions: BSREM in the setting of ⁶⁸Ga PMSA PET staging or restaging is comparable to OSEM. Full article

(This article belongs to the Special Issue PSMA in Prostate Cancer)

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15 pages, 1521 KiB

Open AccessArticle

⁶⁸Ga-PSMA PET/CT for Patients with PSA Relapse after Radical Prostatectomy or External Beam Radiotherapy

by Finn Edler von Eyben, Cigdem Soydal and Rie von Eyben

Diagnostics 2021, 11(4), 622; https://doi.org/10.3390/diagnostics11040622 - 30 Mar 2021

Cited by 6 | Viewed by 1751

Abstract

The study aimed to summarize clinical characteristics associated with Gallium-68-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (⁶⁸Ga-PSMA PET/CT) scans as patients were restaged for prostate-specific antigen (PSA) relapse after radical prostatectomy (RP) or external beam radiotherapy (EBRT). Our analyses included [...] Read more.

The study aimed to summarize clinical characteristics associated with Gallium-68-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (⁶⁸Ga-PSMA PET/CT) scans as patients were restaged for prostate-specific antigen (PSA) relapse after radical prostatectomy (RP) or external beam radiotherapy (EBRT). Our analyses included multiple cox regression analyses. The study evaluated 95 patients with rising values of PSAs after RP and after EBRT. Sixty 63% of patients had a positive ⁶⁸Ga-PSMA PET/CT scan. Twelve patients (13%) had a positive site in the prostate bed, 29 patients (30%) had a positive site in the regional lymph nodes, and 19 (20%) had positive sites in distant organs. After four years follow-up, 21 patients (22%) died. Using multiple Cox regression analyses, the number of positive sites on the ⁶⁸Ga-PSMA PET/CT scan significantly predicted overall survival (OS) (p = 0.0001), whereas risk score and regional locations of the positive sites were not significant in the multiple Cox regression analyses. Our study indicates that the specific findings of ⁶⁸Ga-PSMA PET/CT scans are important because detailed findings of the scans predict the outcome after salvage treatment of patients with PSA relapse examined with ⁶⁸Ga-PSMA PET/CT scans. Full article

(This article belongs to the Special Issue PSMA in Prostate Cancer)

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11 pages, 4777 KiB

Open AccessArticle

68Ga-PSMA-11 PET/CT Follow-Up of Patients with Prostate Cancer with Bone Metastases Who Had Reduced Bone Density after Androgen Deprivation Therapy

by Mikhail Kesler, Ido Druckmann, Charles Levine, Jonathan Kuten, Ofer Yossepowitch and Einat Even-Sapir

Diagnostics 2021, 11(2), 277; https://doi.org/10.3390/diagnostics11020277 - 10 Feb 2021

Cited by 3 | Viewed by 1826

Abstract

Bone metastases from prostate cancer (PCa) often show an increase in density on computed tomography (CT) after successful androgen deprivation therapy (ADT). Density may be reduced, however, as the disease progresses or, contrarily, when disease is no longer active. The current study investigated [...] Read more.

Bone metastases from prostate cancer (PCa) often show an increase in density on computed tomography (CT) after successful androgen deprivation therapy (ADT). Density may be reduced, however, as the disease progresses or, contrarily, when disease is no longer active. The current study investigated the role of 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) in differentiating between these two conditions. Methods: The study cohort included 15 PCa patients with sclerotic/blastic bone metastasis in whom reduction in bone density of metastasis was noted on follow-up 68Ga-PSMA-11 PET/CT after ADT. Each patient had two PET/CT scans. Prior to the first scan, six patients were castration naïve and nine patients were already treated. All patients had ADT between the two PET/CT scans. PET parameters (SUVmax and tumor-to-background ratio), and CT parameters (HUmax) were determined and compared for each lesion on both scans. Patient’s response was based on prostate-specific antigen (PSA) levels and appearance of new lesions. The Kolmogorov–Smirnov test was used to evaluate normal distribution of the continuous variables. Results: Post-ADT reduction in bone density was identified in 37 lesions. The mean HUmax was 883.9 ± 175.1 on the first scan and 395.6 ± 157.1 on the second scan (p < 0.001). Twenty-one of the 37 lesions showed no increased tracer uptake on the second PET/CT scan raising the likelihood of a response. The other 16 lesions were associated with increased uptake suggestive of an active resistant disease. Bone density was not different in lesions that no longer showed an increased uptake as compared with those that did. Seven of the study patients responded to therapy, and none of the 16 lesions found in these patients showed increased 68Ga-PSMA-11 uptake. In eight patients with progressive disease, all 12 lesions in five of them showed increased 68Ga-PSMA-11 uptake, there was mixed response in two patients (having two lesions with increased uptake and one without) and although all three lesions no longer showed an increased uptake, new lesions were detected in the eighth patient. Conclusion: A decrease in density of bone lesions may reflect clinical progression, or contrarily, a response to therapy in patients with PCa and skeletal involvement treated with ADT. Uptake of 68Ga-PSMA-11 may separate between these two vastly opposing conditions. Full article

(This article belongs to the Special Issue PSMA in Prostate Cancer)

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Review

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12 pages, 285 KiB

Open AccessReview

Biomarkers in Prostate-Specific Membrane Antigen Theranostics

by Panagiotis J. Vlachostergios, Ioannis Zachos and Vassilios Tzortzis

Diagnostics 2021, 11(6), 1108; https://doi.org/10.3390/diagnostics11061108 - 18 Jun 2021

Cited by 5 | Viewed by 1995

Abstract

Theranostics of prostate cancer (PC) represents a growing area of development of imaging agents and targeted radionuclide therapeutics against a major target, prostate specific membrane antigen (PSMA). In view of the encouraging efficacy from the use of ¹⁷⁷Lu and other radionuclides in [...] Read more.

Theranostics of prostate cancer (PC) represents a growing area of development of imaging agents and targeted radionuclide therapeutics against a major target, prostate specific membrane antigen (PSMA). In view of the encouraging efficacy from the use of ¹⁷⁷Lu and other radionuclides in metastatic castration-resistant prostate cancer (mCRPC), it is becoming increasingly important to identify surrogate markers that can help predict which patients are more likely to respond and experience improved survival. This review discusses potential predictors of efficacy of PSMA-targeted radionuclide therapies (TRT) segregated in three major categories: imaging, clinical and molecular. Full article

(This article belongs to the Special Issue PSMA in Prostate Cancer)

15 pages, 541 KiB

Open AccessReview

Diagnostic Role of ¹⁸F-PSMA-1007 PET/CT in Prostate Cancer Staging: A Systematic Review

by Salam Awenat, Arnoldo Piccardo, Patricia Carvoeiras, Giovanni Signore, Luca Giovanella, John O. Prior and Giorgio Treglia

Diagnostics 2021, 11(3), 552; https://doi.org/10.3390/diagnostics11030552 - 19 Mar 2021

Cited by 39 | Viewed by 5763

Abstract

Background: The use of prostate-specific membrane antigen (PSMA)-targeted agents for staging prostate cancer (PCa) patients using positron emission tomography/computed tomography (PET/CT) is increasing worldwide. We performed a systematic review on the role of ¹⁸F-PSMA-1007 PET/CT in PCa staging to provide evidence-based data [...] Read more.

Background: The use of prostate-specific membrane antigen (PSMA)-targeted agents for staging prostate cancer (PCa) patients using positron emission tomography/computed tomography (PET/CT) is increasing worldwide. We performed a systematic review on the role of ¹⁸F-PSMA-1007 PET/CT in PCa staging to provide evidence-based data in this setting. Methods: A comprehensive computer literature search of PubMed/MEDLINE and Cochrane Library databases for studies using ¹⁸F-PSMA-1007 PET/CT in PCa staging was performed until 31 December 2020. Eligible articles were selected and relevant information was extracted from the original articles by two authors independently. Results: Eight articles (369 patients) evaluating the role of ¹⁸F-PSMA-1007 PET/CT in PCa staging were selected. These studies were quite heterogeneous, but, overall, they demonstrated a good diagnostic accuracy of ¹⁸F-PSMA-1007 PET/CT in detecting PCa lesions at staging. Overall, higher primary PCa aggressiveness was associated with higher ¹⁸F-PSMA-1007 uptake. When compared with other radiological and scintigraphic imaging methods, ¹⁸F-PSMA-1007 PET/CT had superior sensitivity in detecting metastatic disease and the highest inter-reader agreement. ¹⁸F-PSMA-1007 PET/CT showed similar results in terms of diagnostic accuracy for PCa staging compared with PET/CT with other PSMA-targeted tracers. Dual imaging with multi-parametric magnetic resonance imaging and ¹⁸F-PSMA-1007 PET/CT may improve staging of primary PCa. Notably, ¹⁸F-PSMA-1007-PET/CT may detect metastatic disease in a significant number of patients with negative standard imaging. Conclusions: ¹⁸F-PSMA-1007 PET/CT demonstrated a good accuracy in PCa staging, with similar results compared with other PSMA-targeted radiopharmaceuticals. This method could substitute bone scintigraphy and conventional abdominal imaging for PCa staging. Prospective multicentric studies are needed to confirm these findings. Full article

(This article belongs to the Special Issue PSMA in Prostate Cancer)

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11 pages, 2873 KiB

Open AccessBrief Report

Efficacy and Haematologic Toxicity of Palliative Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen in Heavily Pre-Treated Patients

by Murali Kesavan, Danielle Meyrick, Marat Gallyamov, J. Harvey Turner, Sharon Yeo, Giuseppe Cardaci and Nat P. Lenzo

Diagnostics 2021, 11(3), 515; https://doi.org/10.3390/diagnostics11030515 - 14 Mar 2021

Cited by 8 | Viewed by 5688

Abstract

Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy (¹⁷⁷Lu-PSMA RLT) is an effective salvage treatment. However, studies have highlighted haematologic toxicity as an adverse event of concern. We report [...] Read more.

Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy (¹⁷⁷Lu-PSMA RLT) is an effective salvage treatment. However, studies have highlighted haematologic toxicity as an adverse event of concern. We report our single-centre experience of compassionate access palliative ¹⁷⁷Lu-DOTAGA-(I-y)fk(Sub-KuE) (¹⁷⁷Lu-PSMA I&T) with respect to efficacy and haematologic safety. Methods: Patients with mCRPC and adequate bone marrow/liver function were included. All patients included underwent baseline and response assessment by Gallium-68-PSMA-11 positron emission tomography/computed tomography (⁶⁸Ga-PSMA-11 PET/CT). Prescribed activity of therapy was a median 6.24 GBq per patient per cycle (IQR1.29 GBq), administered in 8-week intervals, up to four cycles. Response was assessed by prostate specific antigen (PSA) and a week-12 PET/CT. Incidence of grade ≥ 3 haematologic toxicity, including association with risk factors (age ≥ 70 years, prior/concurrent therapy, presence of metastases, and number of cycles completed), was analysed. Results: One hundred patients completed one cycle of ¹⁷⁷Lu PSMA I&T and underwent response assessment by both PSA and PET/CT. Two patients had an uninterpretable week-12 PET/CT. Median age was 70 (50–89), median number of prior therapies was three (1–6), and median follow up was 12-months. Fifty-four percent achieved a PSA response. Disease control rate (DCR) by PET/CT was 64% (29% SD, 34% PR, and 1% CR). Disease control by PET/CT was associated with an improved one-year overall survival (OS) compared to non-responders, median OS not-reached vs 10-months (p < 0.0001; 95% CI: 0.08–0.44). Regarding haematologic toxicity, 11% experienced a grade ≥ 3 cytopenia (self-limiting). No cases of myelodysplasia/acute leukaemia (MDS/AL) have been recorded. No association with risk factors was demonstrated. Conclusion: ¹⁷⁷Lu-PSMA I&T is a safe and effective palliative outpatient treatment for mCRPC. ⁶⁸Ga-PSMA-11 PET/CT response is associated with an improved one-year OS and may be used to adapt therapy. Full article

(This article belongs to the Special Issue PSMA in Prostate Cancer)

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