Single-time-point dosimetry using model selection and the Bayesian fitting method: A proof of concept.

Purpose: This study aimed to determine the effect of model selection on simplified dosimetry for the kidneys using Bayesian fitting (BF) and single-time-point (STP) imaging.

Methods: Kidney biokinetics data of [Lu]Lu-PSMA-617 from mHSPC were collected using SPECT/CT after injection of (3.1 ± 0.

[F]PSMA-1007 PET for biochemical recurrence of prostate cancer, a comparison with [F]Fluciclovine.

Aim: The objective of this study was to compare the detection rates of [F]PSMA-1007 and [F]Fluciclovine in early biochemical recurrence (BCR) of prostate cancer, i.e. with low prostate-specific antigen (PSA) levels (0.

Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial.

Background: [Lu]Lu-PSMA-617 (Lu-PSMA-617) prolongs radiographic progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer previously treated with androgen receptor pathway inhibitor (ARPI) and taxane therapy. We aimed to investigate the efficacy of Lu-PSMA-617 in patients with taxane-naive metastatic castration-resistant prostate cancer.

Methods: In this phase 3, randomised, controlled trial conducted at 74 sites across Europe and North America, taxane-naive patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer who had progressed once on a previous ARPI were randomly allocated (1:1) to open-label, intravenous Lu-PSMA-617 at a dosage of 7·4 GBq (200 mCi) ± 10% once every 6 weeks for six cycles, or a change of ARPI (to abiraterone or enzalutamide, administered orally on a continuous basis per product labelling).

Impact of loss-of-function alterations on the response to PSMA radioligand therapy in metastatic castration-resistant prostate cancer patients.

PSMA-targeting radioligand therapy (PSMA-RLT) has shown promise in metastatic castration-resistant prostate cancer (mCRPC), particularly in PSMA-avid tumours. However, predicting response remains challenging. Preclinical data suggests aberrant p53-signalling as a predictor of poor response.

Digoxin treatment does not reinduce radioiodine uptake in radioiodine refractory non-medullary thyroid carcinoma.

Objective: Patients with non-medullary thyroid carcinoma (NMTC) that are refractory to radioactive iodine (RAI) have a poor prognosis. Strategies for restoring the ability to take up iodine, so-called redifferentiation, are promising but not suitable for all patients. Preclinical studies, in human cell lines just as in a murine model, have shown that the cardiac glycoside digoxin restored RAI uptake.

Correlation analyses of radiographic progression-free survival with clinical and health-related quality of life outcomes in metastatic castration-resistant prostate cancer: Analysis of the phase 3 VISION trial.

Background: [Lu]Lu-PSMA-617 (Lu-PSMA-617) plus protocol-permitted standard of care (SOC) prolonged overall survival (OS) and radiographic progression-free survival (rPFS) versus SOC in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 VISION study, in addition to beneficial effects on symptomatic skeletal events (SSEs) and health-related quality of life (HRQOL).

Methods: Post hoc analyses used the full analysis set from the VISION study (N = 831) overall and by randomized treatment arm (Lu-PSMA-617 plus SOC, n = 551; SOC, n = 280). Correlations were determined between OS and rPFS and between rPFS or OS and time to SSE or to worsening HRQOL (Functional Assessment of Cancer Therapy-Prostate [FACT-P] and 5-level EQ-5D [EQ-5D-5L]).

Multiparametric MRI and F-PSMA-1007 PET/CT for the Detection of Clinically Significant Prostate Cancer.

Background Multiparametric MRI (mpMRI) is effective for detecting prostate cancer (PCa); however, there is a high rate of equivocal Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions and false-positive findings. Purpose To investigate whether fluorine 18 (F) prostate-specific membrane antigen (PSMA) 1007 PET/CT after mpMRI can help detect localized clinically significant PCa (csPCa), particularly for equivocal PI-RADS 3 lesions. Materials and Methods This prospective study included participants with elevated prostate-specific antigen (PSA) levels referred for prostate mpMRI between September 2020 and February 2022.

Bone marrow dosimetry in low volume mHSPC patients receiving Lu-177-PSMA therapy using SPECT/CT.

Background: Bone marrow toxicity in advanced prostate cancer patients who receive [Lu]Lu-PSMA-617 is a well-known concern. In early stage patients; e.g.

The Impact of Baseline PSMA PET/CT Versus CT on Outcomes of Ra Therapy in Metastatic Castration-Resistant Prostate Cancer Patients.

Imaging before Ra-dichloride (Ra) therapy is crucial for selecting metastatic castration-resistant prostate cancer (mCRPC) patients with bone-only disease. The purpose of this study was to evaluate if baseline prostate-specific membrane antigen (PSMA) PET/CT (bPSMA) versus CT is associated with outcomes of Ra therapy. A secondary analysis of the data of a prospective observational study (NCT04995614) was performed.

Adjuvant dendritic cell therapy in stage IIIB/C melanoma: the MIND-DC randomized phase III trial.

Autologous natural dendritic cells (nDCs) treatment can induce tumor-specific immune responses and clinical responses in cancer patients. In this phase III clinical trial (NCT02993315), 148 patients with resected stage IIIB/C melanoma were randomized to adjuvant treatment with nDCs (n = 99) or placebo (n = 49). Active treatment consisted of intranodally injected autologous CD1c+ conventional and plasmacytoid DCs loaded with tumor antigens.

The Potential Contribution of Radiopharmaceutical Therapies in Managing Oligometastatic Disease.

There is a growing understanding of the oligometastatic disease state, characterized by the presence of 5 or fewer lesions. Advanced molecular imaging techniques, such as prostate-specific membrane antigen PET, refines the ability to detect oligometastatic recurrences (oligorecurrences) early. These developments have led to the exploration of metastasis-directed therapy (MDT) in oligorecurrent disease as an alternative to or as a means of delaying systemic therapy.

PET Imaging and Protein Expression of Prostate-Specific Membrane Antigen in Glioblastoma: A Multicenter Inventory Study.

Upregulation of prostate-specific membrane antigen (PSMA) in neovasculature has been described in glioblastoma multiforme (GBM), whereas vasculature in nonaffected brain shows hardly any expression of PSMA. It is unclear whether PSMA-targeting tracer uptake on PET is based on PSMA-specific binding to neovasculature or aspecific uptake in tumor. Here, we quantified uptake of various PSMA-targeting tracers in GBM and correlated this with PSMA expression in tumor biopsy samples from the same patients.

Click-to-Release: Cleavable Radioimmunoimaging with [Zr]Zr-DFO--Cyclooctene-Trastuzumab Increases Tumor-to-Blood Ratio.

One of the main challenges of PET imaging with Zr-labeled monoclonal antibodies (mAbs) remains the long blood circulation of the radiolabeled mAbs, leading to high background signals, decreasing image quality. To overcome this limitation, here we report the use of a bioorthogonal linker cleavage approach (click-to-release chemistry) to selectively liberate [Zr]Zr-DFO from -cyclooctene-functionalized trastuzumab (TCO-Tmab) in blood, following the administration of a tetrazine compound (trigger) in BT-474 tumor-bearing mice. We created a series of TCO-DFO constructs and evaluated their performance in [Zr]Zr-DFO release from Tmab using different trigger compounds.

Urinary excretion kinetics of [Lu]Lu-PSMA-617.

Introduction: For the implementation of suitable radiation safety measures in [Lu]Lu-PSMA-617 therapy, additional insight into excretion kinetics is important. This study evaluates this kinetics in prostate cancer patients via direct urine measurements.

Methods: Both the short-term (up to 24 h, n = 28 cycles) and long-term kinetics (up to 7 weeks, n = 35 samples) were evaluated by collection of urine samples.

Health-related quality of life and pain outcomes with [Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial.

Background: In VISION, the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy lutetium-177 [Lu]Lu-PSMA-617 (vipivotide tetraxetan) improved radiographic progression-free survival and overall survival when added to protocol-permitted standard of care in patients with metastatic castration-resistant prostate cancer. Here, we report additional health-related quality of life (HRQOL), pain, and symptomatic skeletal event results.

Methods: This multicentre, open-label, randomised, phase 3 trial was conducted at 84 cancer centres in nine countries in North America and Europe.

A VISION Substudy of Reader Agreement on Ga-PSMA-11 PET/CT Scan Interpretation to Determine Patient Eligibility for Lu-PSMA-617 Radioligand Therapy.

[ Ga]Ga-PSMA-11 ( Ga-PSMA-11) is used to identify prostate-specific membrane antigen (PSMA)-positive tumors on PET scans. In the VISION study, Ga-PSMA-11 was used to determine the eligibility of patients with metastatic castration-resistant prostate cancer for treatment with [Lu]Lu-PSMA-617 (Lu-PSMA-617), based on predefined read criteria. This substudy aimed to investigate the interreader variability and intrareader reproducibility of visual assessments of Ga-PSMA-11 PET/CT scans using the VISION read criteria and evaluate the agreement between read results for this and the VISION study.

Head-To-Head Comparison of PET and Perfusion Weighted MRI Techniques to Distinguish Treatment Related Abnormalities from Tumor Progression in Glioma.

The post-treatment imaging surveillance of gliomas is challenged by distinguishing tumor progression (TP) from treatment-related abnormalities (TRA). Sophisticated imaging techniques, such as perfusion-weighted magnetic resonance imaging (MRI PWI) and positron-emission tomography (PET) with a variety of radiotracers, have been suggested as being more reliable than standard imaging for distinguishing TP from TRA. However, it remains unclear if any technique holds diagnostic superiority.

Tumoral Ki67 and PSMA Expression in Fresh Pre-PSMA-RLT Biopsies and Its Relation With PSMA-PET Imaging and Outcomes of PSMA-RLT in Patients With mCRPC.

Introduction: Prostate specific membrane antigen (PSMA) directed radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. However, it is still poorly understood why approximately 40% of the patients does not respond to PSMA-RLT. The aims of this study were to evaluate the pretreatment PSMA expression on immunohistochemistry (IHC) and PSMA uptake on PET/CT imaging in mCRPC patients who underwent PSMA-RLT.

Costs of radium-223 and the pharmacy preparation Lu-PSMA-I&T for metastatic castration-resistant prostate cancer in Dutch hospitals.

Objective: The radiopharmaceuticals radium-223 and the pharmacy preparation Lu-PSMA-I&T are reimbursed in the Netherlands for metastatic castration-resistant prostate cancer (mCRPC) treatment. Although shown to be life-prolonging in patients with mCRPC, the treatment procedures associated with these radiopharmaceuticals can be challenging for both patients and hospitals. This study investigates the costs of mCRPC treatment in Dutch hospitals for currently reimbursed radiopharmaceuticals with a demonstrated overall survival benefit.

Fibroblast activation protein-targeted radionuclide therapy: background, opportunities, and challenges of first (pre)clinical studies.

Introduction: Fibroblast activation protein (FAP) is highly overexpressed in stromal tissue of various cancers. While FAP has been recognized as a potential diagnostic or therapeutic cancer target for decades, the surge of radiolabeled FAP-targeting molecules has the potential to revolutionize its perspective. It is presently hypothesized that FAP targeted radioligand therapy (TRT) may become a novel treatment for various types of cancer.

Optimization of the radiation dosimetry protocol in Lutetium-177-PSMA therapy: toward clinical implementation.

Background: Dosimetry in [Lu]Lu-PSMA therapy is a valuable tool to assess treatment efficacy and toxicity. This study aims to develop a clinically implementable protocol to determine the absorbed dose in organs and tumor lesions after [Lu]Lu-PSMA-617 therapy, by reducing the imaging time points and utilizing population-based kinetics with a single scan, with evaluation of its influence on the uncertainty in absorbed dose.

Methods: Ten patients with metastatic hormone-sensitive prostate cancer received two cycles of [Lu]Lu-PSMA-617.