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Cancers May 2024The objective of this retrospective study is to assess the effectiveness and safety of two beta-emitting prostate-specific membrane antigen (PSMA) radioligands, [Lu]Lu...
The objective of this retrospective study is to assess the effectiveness and safety of two beta-emitting prostate-specific membrane antigen (PSMA) radioligands, [Lu]Lu and [161Tb]Tb, in heavily treated patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 148 cycles of beta-emitting PSMA radioligand therapy were given to 53 patients at a specialized cancer care center in Amman, Jordan. This treatment was offered following the exhaustion of all prior treatment modalities. Approximately half of the cases (n = 26) demonstrated an initial partial response to PSMA radioligand therapy. Moreover, roughly one-fourth of the patients (n = 13) exhibited a sustained satisfactory biochemical response, which qualified them to receive a total of six PSMA radioligand therapy cycles and maintain continued follow-up for additional treatment cycles. This was reflected by an adequate prostate-specific antigen (PSA) decline and a concomitant partial response evident on [Ga]Ga-PSMA positron emission tomography/computed tomography imaging. A minority of patients (n= 18; 34%) experienced side effects. Generally, these were low-grade and self-limiting toxicities. This study endorses previous research evidence about PSMA radioligand therapy's safety and efficacy. It also provides the first clinical insight from patients of Arab ethnicity. This should facilitate and promote further evidence, both regionally and internationally.
PubMed: 38893095
DOI: 10.3390/cancers16111974 -
International Journal of Molecular... May 2024Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA)...
Astatine (At) is a cyclotron-produced alpha emitter with a physical half-life of 7.2 h. In our previous study, the At-labeled prostate-specific membrane antigen (PSMA) compound ([At]PSMA-5) exhibited excellent tumor growth suppression in a xenograft model. We conducted preclinical biodistribution and toxicity studies for the first-in-human clinical trial. [At]PSMA-5 was administered to both normal male ICR mice ( = 85) and cynomolgus monkeys ( = 2). The mice were divided into four groups for the toxicity study: 5 MBq/kg, 12 MBq/kg, 35 MBq/kg, and vehicle control, with follow-ups at 1 day ( = 10 per group) and 14 days ( = 5 per group). Monkeys were observed 24 h post-administration of [At]PSMA-5 (9 MBq/kg). Blood tests and histopathological examinations were performed at the end of the observation period. Blood tests in mice indicated no significant myelosuppression or renal dysfunction. However, the monkeys displayed mild leukopenia 24 h post-administration. Despite the high accumulation in the kidneys and thyroid, histological analysis revealed no abnormalities. On day 1, dose-dependent single-cell necrosis/apoptosis was observed in the salivary glands of mice and intestinal tracts of both mice and monkeys. Additionally, tingible body macrophages in the spleen and lymph nodes indicated phagocytosis of apoptotic B lymphocytes. Cortical lymphopenia (2/10) in the thymus and a decrease in the bone marrow cells (9/10) were observed in the 35 MBq/kg group in mice. These changes were transient, with no irreversible toxicity observed in mice 14 days post-administration. This study identified no severe toxicities associated with [At]PSMA-5, highlighting its potential as a next-generation targeted alpha therapy for prostate cancer. The sustainable production of At using a cyclotron supports its applicability for clinical use.
Topics: Animals; Male; Prostatic Neoplasms; Mice; Tissue Distribution; Mice, Inbred ICR; Astatine; Alpha Particles; Humans; Macaca fascicularis; Glutamate Carboxypeptidase II; Radiopharmaceuticals
PubMed: 38891856
DOI: 10.3390/ijms25115667 -
Healthcare (Basel, Switzerland) May 2024Globally, prostate cancer is the second leading cause of cancer deaths among males. It is the most commonly diagnosed cancer in Australia. The quality of life of...
BACKGROUND
Globally, prostate cancer is the second leading cause of cancer deaths among males. It is the most commonly diagnosed cancer in Australia. The quality of life of prostate cancer patients is poorer when compared to the general population due to the disease itself and its related complications. However, there is limited research on the geographic pattern of quality of life and its risk factors in Victoria. Therefore, an examination of the spatio-temporal pattern and risk factors of poor quality of life, along with the impact of spatial weight matrices on estimates and model performance, was conducted.
METHOD
A retrospective study was undertaken based on the Prostate Cancer Outcome Registry-Victoria data. Patient data ( = 5238) were extracted from the Prostate Cancer Outcome Registry, a population-based clinical quality outcome assessment from 2015 to 2021. A Bayesian spatio-temporal multilevel model was fitted to identify risk factors for poor quality of life. This study also evaluated the impact of distance- and adjacency-based spatial weight matrices. Model convergence was assessed using Gelman-Rubin statistical plots, and model comparison was based on the Watanabe-Akaike Information Criterion.
RESULTS
A total of 1906 (36.38%) prostate cancer patients who had undergone surgery experienced poor quality of life in our study. Belonging to the age group between 76 and 85 years (adjusted odds ratio (AOR) = 2.90, 95% credible interval (CrI): 1.39, 2.08), having a prostate-specific antigen level between 10.1 and 20.0 (AOR = 1.33, 95% CrI: 1.12, 1.58), and being treated in a public hospital (AOR = 1.35, 95% CrI: 1.17, 1.53) were significantly associated with higher odds of poor quality of life. Conversely, residing in highly accessible areas (AOR = 0.60, 95% CrI: 0.38, 0.94) was significantly associated with lower odds of poor prostate-specific antigen levels. Variations in estimates and model performance were observed depending on the choice of spatial weight matrices.
CONCLUSION
Belonging to an older age group, having a high prostate-specific antigen level, receiving treatment in public hospitals, and remoteness were statistically significant factors linked to poor quality of life. Substantial spatio-temporal variations in poor quality of life were observed in Victoria across local government areas. The distance-based weight matrix performed better than the adjacency-based matrix. This research finding highlights the need to reduce geographical disparities in quality of life. The statistical methods developed in this study may also be useful to apply to other population-based clinical registry settings.
PubMed: 38891168
DOI: 10.3390/healthcare12111093 -
EBioMedicine Jun 2024The accuracy of blood-based early tumour recognition is compromised by signal production at non-tumoral sites, low amount of signal produced by small tumours, and...
BACKGROUND
The accuracy of blood-based early tumour recognition is compromised by signal production at non-tumoral sites, low amount of signal produced by small tumours, and variable tumour production. Here we examined whether tumour-specific enhancement of vascular permeability by the particular tumour homing peptide, iRGD, which carries dual function of binding to integrin receptors overexpressed in the tumour vasculature and is known to promote extravasation via neuropilin-1 receptor upon site-specific cleavage, might be useful to improve blood-based tumour detection by inducing a yet unrecognised vice versa tumour-to-blood transport.
METHODS
To detect an iRGD-induced tumour-to-blood transport, we examined the effect of intravenously injected iRGD on blood levels of α-fetoprotein (AFP) and autotaxin in several mouse models of hepatocellular carcinoma (HCC) or in mice with chronic liver injury without HCC, and on prostate-specific antigen (PSA) levels in mice with prostate cancer.
FINDINGS
Intravenously injected iRGD rapidly and robustly elevated the blood levels of AFP in several mouse models of HCC, but not in mice with chronic liver injury. The effect was primarily seen in mice with small tumours and normal basal blood AFP levels, was attenuated by an anti-neuropilin-1 antibody, and depended on the concentration gradient between tumour and blood. iRGD treatment was also able to increase blood levels of autotaxin in HCC mice, and of PSA in mice with prostate cancer.
INTERPRETATION
We conclude that iRGD induces a tumour-to-blood transport in a tumour-specific fashion that has potential of improving diagnosis of early stage cancer.
FUNDING
Deutsche Krebshilfe, DKTK, LOEWE-Frankfurt Cancer Institute.
PubMed: 38889481
DOI: 10.1016/j.ebiom.2024.105178 -
Insights Into Imaging Jun 2024To investigate the diagnostic performance of MRI in detecting clinically significant prostate cancer (csPCa) and prostate cancer (PCa) in patients with prostate-specific...
OBJECTIVE
To investigate the diagnostic performance of MRI in detecting clinically significant prostate cancer (csPCa) and prostate cancer (PCa) in patients with prostate-specific antigen (PSA) levels of 4-10 ng/mL.
METHODS
A computerized search of PubMed, Embase, Cochrane Library, Medline, and Web of Science was conducted from inception until October 31, 2023. We included articles on the use of MRI to detect csPCa or PCa at 4-10 ng/mL PSA. The primary and secondary outcomes were MRI performance in csPCa and PCa detection, respectively; the estimates of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were pooled in a bivariate random-effects model.
RESULTS
Among the 19 studies (3879 patients), there were 10 (2205 patients) and 13 studies (2965 patients) that reported MRI for detecting csPCa or PCa, respectively. The pooled sensitivity and specificity for csPCa detection were 0.84 (95% confidence interval [CI], 0.79-0.88) and 0.76 (95%CI, 0.65-0.84), respectively, for PCa detection were 0.82 (95%CI, 0.75-0.87) and 0.74 (95%CI, 0.65-0.82), respectively. The pooled NPV for csPCa detection was 0.91 (0.87-0.93). Biparametric magnetic resonance imaging also showed a significantly higher sensitivity and specificity relative to multiparametric magnetic resonance imaging (both p < 0.01).
CONCLUSION
Prostate MRI enables the detection of csPCa and PCa with satisfactory performance in the PSA gray zone. The excellent NPV for csPCa detection indicates the possibility of biopsy decision-making in patients in the PSA gray zone, but substantial heterogeneity among the included studies should be taken into account.
CLINICAL RELEVANCE STATEMENT
Prostate MRI can be considered a reliable and satisfactory tool for detecting csPCa and PCa in patients with PSA in the "gray zone", allowing for reducing unnecessary biopsy and optimizing the overall examination process.
KEY POINTS
Prostate-specific antigen (PSA) is a common screening tool for prostate cancer but risks overdiagnosis. MRI demonstrated excellent negative predictive value for prostate cancer in the PSA gray zone. MRI can influence decision-making for these patients, and biparametric MRI should be further evaluated.
PubMed: 38886256
DOI: 10.1186/s13244-024-01699-4 -
EJNMMI Radiopharmacy and Chemistry Jun 2024Prostate cancer is a common cancer among men worldwide that has a very poor prognosis, especially when it progresses to metastatic castration-resistant prostate cancer...
BACKGROUND
Prostate cancer is a common cancer among men worldwide that has a very poor prognosis, especially when it progresses to metastatic castration-resistant prostate cancer (mCRPC). Therefore, novel therapeutic agents for mCRPC are urgently required. Because prostate-specific membrane antigen (PSMA) is overexpressed in mCRPC, targeted alpha therapy (TAT) for PSMA is a promising treatment for mCRPC. Astatine-211 (At) is a versatile α-emitting radionuclide that can be produced using a cyclotron. Therefore, At-labeled PSMA compounds could be useful for TAT; however, At-labeled compounds are unstable against deastatination in vivo. In this study, to develop in vivo stable At-labeled PSMA derivatives, we designed and synthesized At-labeled PSMA derivatives using a neopentyl glycol (NpG) structure that can stably retain At in vivo. We also evaluated their biodistribution in normal and tumor-bearing mice.
RESULTS
We designed and synthesized At-labeled PSMA derivatives containing two glutamic acid (Glu) linkers between the NpG structure and asymmetric urea (NpG-L-PSMA ((L-Glu) linker used) and NpG-D-PSMA ((D-Glu) linker used)). First, we evaluated the characteristics of I-labeled NpG derivatives because I was readily available. [I]I-NpG-L-PSMA and [I]I-NpG-D-PSMA showed low accumulation in the stomach and thyroid, indicating their high in vivo stability against deiodination. [I]I-NpG-L-PSMA was excreted in urine as hydrophilic radiometabolites in addition to the intact form. Meanwhile, [I]I-NpG-D-PSMA was excreted in urine in an intact form. In both cases, no radioactivity was observed in the free iodine fraction. [I]I-NpG-D-PSMA showed higher tumor accumulation than [I]I-NpG-L-PSMA. We then developed At-labeled PSMA using the NpG-D-PSMA structure. [At]At-NpG-D-PSMA showed low accumulation in the stomach and thyroid in normal mice, indicating its high stability against deastatination in vivo. Moreover, [At]At-NpG-D-PSMA showed high accumulation in tumor similar to that of [I]I-NpG-D-PSMA.
CONCLUSIONS
[At]At-NpG-D-PSMA showed high in vivo stability against deastatination and high tumor accumulation. [At]At-NpG-D-PSMA should be considered as a potential new TAT for mCRPC.
PubMed: 38884866
DOI: 10.1186/s41181-024-00278-8 -
Frontiers in Medicine 2024Renal arteriovenous malformations (rAVMs) are congenital abnormal pathways between renal arteries and veins that are rare in the general population. It is often...
BACKGROUND
Renal arteriovenous malformations (rAVMs) are congenital abnormal pathways between renal arteries and veins that are rare in the general population. It is often misdiagnosed as malignant renal tumors with abundant blood supply, and the definitive diagnosis primarily relies on angiography. Multimodality imaging, including contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT plays an important role in the differential diagnosis of renal space-occupying lesions.
CASE PRESENTATION
A 56-year-old man presented with abdominal distension, loss of appetite, and back pain without obvious cause 2 years ago, without nausea vomiting, or frequent urination. Gastroscopy and colonoscopy showed multiple polyps in the duodenum and colon. Abdomen contrast-enhanced CT revealed a mass of 1.6 × 1.4 cm in the left kidney, which was considered to be a malignant tumor. PET/CT was performed for further diagnosis; the F-fluorodesoxyglucose (F-FDG) PET/CT scan showed mild uptake in the left renal mass, while no uptake of F- prostate-specific membrane antigen (PSMA) was observed. Following a multidisciplinary discussion, the possibility of renal AVMs was considered and subsequently confirmed by renal angiography as the diagnosis. Then, selective segmental renal artery embolization was performed for treatment.
CONCLUSION
Renal AVMs are extremely rare in clinical practice. Due to limited research on the application of F-FDG and F-PSMA PET/CT to renal AVMs, its role remains largely unexplored. With the increasing popularity of PET/CT imaging, comprehensive imaging of the disease has become indispensable. We report the first case of PSMA PET/CT imaging in renal AVMs, and when PSMA expression is absent in a renal mass, the possibility of renal AVMs should be considered.
PubMed: 38882665
DOI: 10.3389/fmed.2024.1420473 -
EJNMMI Research Jun 2024Studies on single-target PET imaging of gastrin-releasing peptide receptor (GRPR), prostate-specific membrane antigen (PSMA), or neurotensin receptor 1(NTR1) have been...
Evaluation of gastrin-releasing peptide receptor, prostate-specific membrane antigen, and neurotensin receptor 1 as potential biomarkers for accurate prostate cancer stratified diagnosis.
BACKGROUND
Studies on single-target PET imaging of gastrin-releasing peptide receptor (GRPR), prostate-specific membrane antigen (PSMA), or neurotensin receptor 1(NTR1) have been reported. However, the performance of these three targets in the progression of PCa remains unclear. Our study aims to compare the expression of GRPR, PSMA, and NTR1 in patients with prostatic intraepithelial neoplasia (PIN), prostate cancer (PCa), and lymph node metastasis. We synthesized molecular probes targeting the markers to achieve a non-invasive precise detection of PCa patients with PET/CT imaging.
METHODS
In this study, the expression of GRPR, PSMA, and NTR1 was evaluated by immunohistochemistry in 34 PIN, 171 PCa, and 22 lymph node metastasis tissues of patients. The correlation between their expression and the clinicopathological parameters of PCa patients was assessed. Sixteen PCa patients with different Gleason scores (GS) underwent dual-tracer (Ga-NOTA-RM26 and Ga-NOTA-PSMA617) PET/CT.
RESULTS
In the PIN stage, the expression of GRPR was significantly higher than that of PSMA and NTR1 (P < 0.001), while NTR1 expression was significantly higher than PSMA and GRPR expression in primary PCa (P = 0.001). High PSMA expression in PCa patients was associated with shorter progression-free survival (P = 0.037) and overall survival (P = 0.035). PCa patients with high GS had higher tumor uptake of Ga-NOTA-PSMA617 than those with low GS (P = 0.001), while PCa patients with low GS had higher tumor uptake of Ga-NOTA-RM26 than those with high GS (P = 0.001).
CONCLUSIONS
This study presents three novel biomarkers (PSMA, GRPR, and NTR1) as imaging agents for PET/CT, and may offer a promising approach for non-invasive precise detection and Gleason grade prediction of PCa patients.
PubMed: 38880858
DOI: 10.1186/s13550-024-01116-3 -
NPJ Precision Oncology Jun 2024Prostate cancer (PCa) seldom metastasizes to the thyroid gland, and only a limited number of cases are documented in the literature. The application of a relatively...
Prostate cancer (PCa) seldom metastasizes to the thyroid gland, and only a limited number of cases are documented in the literature. The application of a relatively recent and highly sensitive imaging technique, prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET/CT), has enhanced the identification of metastatic disease. Nevertheless, as PSMA is expressed in various tissue types, the clinical importance of a PSMA-avid thyroid lesion remains largely uncertain. A minor, yet noteworthy, percentage of these lesions are ultimately determined to be malignant. Here we describe the case of a 70-year-old man with a past medical history of Lynch syndrome who presented to an outpatient oncologic clinic for management of very high risk localized PCa. He developed metastatic recurrence and his disease progressed through several lines of therapy, including immunotherapy and targeted treatments. He was found to have a new, intense PSMA uptake in an existing, previously benign thyroid nodule. Sonographic evaluation revealed changing morphology despite grossly stable size. Repeat biopsy confirmed the unusual finding of PCa metastasis to a known thyroid nodule. The shift in PSMA avidity played a pivotal role in discerning this metastatic deposit. There is a potential risk that such lesions may be inadequately acknowledged. The impact of the patient's Lynch syndrome on this presentation remains uncertain.
PubMed: 38879699
DOI: 10.1038/s41698-024-00619-5 -
BMC Urology Jun 2024Carcinoma in situ of the bladder is a high-grade cancer that originates in the superficial layer of the bladder. It has the potential to invade nearby organs, and it can...
BACKGROUND
Carcinoma in situ of the bladder is a high-grade cancer that originates in the superficial layer of the bladder. It has the potential to invade nearby organs, and it can spread through blood and lymphatic circulation to distant parts of the body.
CASE PRESENTATION
A 58-year-old non-smoker male presented with gross and microscopic hematuria. His family history included his father's recent bladder cancer. Initial investigations showed hematuria, inflammation, negative urine culture, digital rectal examination revealed an enlarged right lobe of the prostate, and an elevated Prostate-Specific Antigen level. Histopathological examination of samples taken from the bladder mucosa and the prostate confirmed urothelial carcinoma in situ in the bladder and prostate. Further evaluation revealed no other metastasis. The tumor was classified as T4aN0M0. The patient underwent radical cystoprostatectomy and histopathological examination showed that the tumor invading the muscularis propria of the bladder as well as the prostatic glands, but no malignancy was found in prostatic urethra and other areas. The patient was discharged three weeks post-operation and completed on adjuvant chemotherapy consisting of Gemcitabine, and Cisplatin to prevent of relapse. The patient is currently in a good healthy.
CONCLUSION
The occurrence of bladder cancer metastasizing to the prostate without involving the prostatic urethra is uncommon and requires precise diagnostic techniques for accurate tumor classification. Early management is advised to enhance the prognosis for the patient.
Topics: Humans; Male; Middle Aged; Urinary Bladder Neoplasms; Prostatic Neoplasms; Carcinoma in Situ; Urethra
PubMed: 38879527
DOI: 10.1186/s12894-024-01516-6