PSMA Radiotheranostics in Prostate Cancer: Principles, Practice, and Future Prospects.

Prostate cancer is a leading cause of cancer-related mortality in men, with metastatic castration-resistant prostate cancer presenting a substantial treatment challenge. The authors focuse on prostate-specific membrane antigen (PSMA) radiotheranostics, particularly lutetium 177 (Lu)-PSMA radioligand therapy, as an emerging treatment modality for metastatic castration-resistant prostate cancer. The U.

Real-world evidence study on the early use of cemiplimab in the UK: REACT-CEMI (Real World evidence of advanced CSCC treatment with cemiplimab).

Background: Cemiplimab was licensed in the United Kingdom (UK) in 2019 for the treatment of patients with locally advanced and metastatic CSCC not suitable for curative surgery or radiotherapy (advanced CSCC [aCSCC]). No UK multi-center studies have investigated the real-world experience of cemiplimab post marketing authorization in aCSCC.

Methods: This non-interventional retrospective study (10 UK centers) involved data collection from medical records of patients with aCSCC who initiated cemiplimab treatment between 2 July 2019 and 30 November 2020.

Imaging and therapy in prostate cancer using prostate specific membrane antigen radioligands.

Prostate specific membrane antigen (PSMA) directed PET imaging has rapidly transformed prostate cancer workup over the past decade and paved the way for a theranostic approach using 177Lu-labelled PSMA radioligand therapy (RLT). This review gives an overview of the underlying principles behind PSMA as a target; the current use of PSMA PET in prostate cancer imaging and benefits compared to conventional imaging; and therapeutic applications including optimisation of patient selection. It also explores the evidence base of PSMA PET for other indications not in routine clinical use and the future of PSMA-directed RLT.

Bench to Bedside Development of [F]Fluoromethyl-(1,2-H)choline ([F]D4-FCH).

Malignant transformation is characterised by aberrant phospholipid metabolism of cancers, associated with the upregulation of choline kinase alpha (CHKα). Due to the metabolic instability of choline radiotracers and the increasing use of late-imaging protocols, we developed a more stable choline radiotracer, [F]fluoromethyl-[1,2-H]choline ([F]D4-FCH). [F]D4-FCH has improved protection against choline oxidase, the key choline catabolic enzyme, via a H/D isotope effect, together with fluorine substitution.

ROLE OF ANDROGEN RECEPTOR-TARGETED AGENTS IN LOCALIZED PROSTATE CANCER.

Anti-androgen therapy continues to be a basic pilar of treatment for both localized and metastatic prostate cancer. The advent of new generation of androgen receptor targeted agents (ARTA) transformed the care of patients with advanced disease. After such a success, the steps were taken to incorporate a new generation of ARTAs into the treatment landscape of localized prostate cancer.

Eligibility for Lu-PSMA Therapy Depends on the Choice of Companion Diagnostic Tracer: A Comparison of Ga-PSMA-11 and Tc-MIP-1404 in Metastatic Castration-Resistant Prostate Cancer.

Lu-prostate-specific membrane antigen-617 (Lu-PSMA-617) is an effective therapy for metastatic castration-resistant prostate cancer (mCRPC), with evidence of improved survival over standard care. The VISION trial inclusion criteria required a metastatic lesion-to-liver ratio of greater than 1 on Ga-PSMA-11 PET scans. We aimed to determine whether an equivalent ratio is suitable for a SPECT tracer, Tc-MIP-1404, and to compare lesion and lesion-to-normal-organ ratios between the 2 radiotracers.

Prostate cancer-Exercise and Metformin Trial (Pre-EMpT): study protocol for a feasibility factorial randomized controlled trial in men with localised or locally advanced prostate cancer.

Background: Evidence from observational studies have shown that moderate intensity physical activity can reduce risk of progression and cancer-specific mortality in participants with prostate cancer. Epidemiological studies have also shown participants taking metformin to have a reduced risk of prostate cancer. However, data from randomised controlled trials supporting the use of these interventions are limited.

Rectal spacers in patients with prostate cancer undergoing radiotherapy: A survey of UK uro-oncologists.

Aim: To understand the awareness and use of rectal spacers for prostate cancer patients undergoing radical radiotherapy in the United Kingdom.

Methods: An expert-devised online questionnaire was completed by members of the British Uro-oncology Group (BUG).

Results: Sixty-three specialists completed the survey (50% of BUG members at that point in time).

A Single-arm Phase II Trial of Neoadjuvant Cabazitaxel and Cisplatin Chemotherapy for Muscle-Invasive Transitional Cell Carcinoma of the Urinary Bladder.

Introduction: Neoadjuvant cisplatin-based combination chemotherapy improves survival in muscle-invasive bladder cancer. However, response rates and survival remain suboptimal. We evaluated the efficacy, safety, and tolerability of cisplatin plus cabazitaxel.

Spatial heterogeneity of radiolabeled choline positron emission tomography in tumors of patients with non-small cell lung cancer: first-in-patient evaluation of [F]fluoromethyl-(1,2-H)-choline.

: The spatio-molecular distribution of choline and its metabolites in tumors is highly heterogeneous. Due to regulation of choline metabolism by hypoxic transcriptional signaling and other survival factors, we envisage that detection of such heterogeneity in patient tumors could provide the basis for advanced localized therapy. However, non-invasive methods to assess this phenomenon in patients are limited.

[F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer.

Background: Angiogenesis is a driver of platinum resistance in ovarian cancer. We assessed the effect of combination pazopanib and paclitaxel followed by maintenance pazopanib in patients with platinum-resistant/refractory ovarian cancer. Integrins αβ and αβ are both upregulated in tumor-associated vasculature.

A phase II trial of cabazitaxel as second line chemotherapy in relapsed locally advanced and/or metastatic carcinoma of the penis.

Objectives: To assess the efficacy and tolerability of cabazitaxel in relapsed penile cancer.

Methods: This Phase II single-arm trial was designed to recruit 17 patients with relapsed penile cancer. The primary endpoint was objective (complete + partial) response rate (ORR; Response Evaluation Criteria in Solid Tumours [RECIST] v1.

Evaluating the prevalence and predictive factors of vasomotor and psychological symptoms in prostate cancer patients receiving hormonal therapy: Results from a single institution experience.

Background & Purpose: The impact of vasomotor symptoms (VMS) occurring in prostate cancer (PC) patients whilst on androgen deprivation therapy (ADT) has not been extensively researched. This longitudinal study sought to assess the VMS and identify any predictive factors.

Material & Methods: Data from 250 PC patients on ADT were prospectively evaluated between January 10 and August 13 using a physician-directed questionnaire, to assess the impact of VMS.

Molecular mechanisms of hypoxia in cancer.

Purpose: Hypoxia is a condition of insufficient oxygen to support metabolism which occurs when the vascular supply is interrupted, or when a tumour outgrows its vascular supply. It is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. This review provides an overview of hypoxia imaging with Positron emission tomography (PET), with an emphasis on the biological relevance, mechanism of action, highlighting advantages, and limitations of the currently available hypoxia radiotracers.

Development and Validation of Consensus Contouring Guidelines for Adjuvant Radiation Therapy for Bladder Cancer After Radical Cystectomy.

Purpose: To develop multi-institutional consensus clinical target volumes (CTVs) and organs at risk (OARs) for male and female bladder cancer patients undergoing adjuvant radiation therapy (RT) in clinical trials.

Methods And Materials: We convened a multidisciplinary group of bladder cancer specialists from 15 centers and 5 countries. Six radiation oncologists and 7 urologists participated in the development of the initial contours.

Positron Emission Tomography Imaging of Tumor Cell Metabolism and Application to Therapy Response Monitoring.

Cancer cells do reprogram their energy metabolism to enable several functions, such as generation of biomass including membrane biosynthesis, and overcoming bioenergetic and redox stress. In this article, we review both established and evolving radioprobes developed in association with positron emission tomography (PET) to detect tumor cell metabolism and effect of treatment. Measurement of enhanced tumor cell glycolysis using 2-deoxy-2-[(18)F]fluoro-D-glucose is well established in the clinic.

New radiotracers in gynecological cancer: beyond ¹⁸F-FDG.

Imaging plays an important role in the management of gynecological cancers. There is a clinical need for noninvasive prognostic biomarkers to provide more detailed tumor characterization at the baseline and/or early during therapy, which may potentially improve outcomes and enable a personalized treatment approach. Imaging parameters derived from PET/CT techniques are emerging as promising imaging biomarkers.

Health-related quality of life in men with metastatic castration-resistant prostate cancer.

Metastatic castration-resistant prostate cancer (MCRPC) is a chronic disease with several therapeutic options. By definition, all approaches to treatment are palliative in intent and improving health-related quality of life (HRQoL) is an important goal of therapy. Several tools exist for the assessment of HRQoL in MCRPC enabling cross-trial comparisons.

Exploiting altered patterns of choline kinase-alpha expression on human prostate tissue to prognosticate prostate cancer.

Aims: Malignant transformation results in overexpression of choline-kinase (CHK) and altered choline metabolism, which is potentially detectable by immunohistochemistry (IHC). We investigated the utility of CHK-alpha (CHKA) IHC as a complement to current diagnostic investigation of prostate cancer by analysing expression patterns in normal (no evidence of malignancy) and malignant human prostate tissue samples.

Methods: As an initial validation, paraffin-embedded prostatectomy specimen blocks with both normal and malignant prostate tissue were analysed for CHKA protein and mRNA expression by western blot and quantitative reverse transcriptase PCR (qRT-PCR), respectively.

3'-Deoxy-3'-¹⁸F-fluorothymidine positron emission tomography as an early predictor of disease progression in patients with advanced and metastatic pancreatic cancer.

Purpose: 3'-Deoxy-3'-(18)F-fluorothymidine (FLT) positron emission tomography (PET) has limited utility in abdominal imaging due to high physiological hepatic uptake of tracer. We evaluated FLT PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT PET/CTKSF) for early prediction of response and survival outcomes in locally advanced and metastatic pancreatic cancer patients receiving gemcitabine-based chemotherapy.

Methods: Dynamic FLT PET/CT data were collected before and 3 weeks after the first cycle of chemotherapy.

Biodistribution and radiation dosimetry of deuterium-substituted 18F-fluoromethyl-[1, 2-2H4]choline in healthy volunteers.

Unlabelled: (11)C-choline and (18)F-fluoromethylcholine ((18)F-FCH) have been used in patients to study tumor metabolic activity in vivo; however, both radiotracers are readily oxidized to respective betaine analogs, with metabolites detectable in plasma soon after injection of the radiotracer. A more metabolically stable FCH analog, (18)F-fluoromethyl-[1,2-(2)H4]choline ((18)F-D4-FCH), based on the deuterium isotope effect, has been developed. We report the safety, biodistribution, and internal radiation dosimetry profiles of (18)F-D4-FCH in 8 healthy human volunteers.

Exploring the potential of [11C]choline-PET/CT as a novel imaging biomarker for predicting early treatment response in prostate cancer.

Objectives: The aim of the study was to assess the effects of neoadjuvant androgen deprivation (NAD) and radical prostate radiotherapy with concurrent androgen deprivation (RT-CAD) on prostatic [C]choline kinetics and thus develop methodology for the use of [C]choline-PET/computed tomography (CT) as an early imaging biomarker.

Materials And Methods: Ten patients with histologically confirmed prostate cancer underwent three sequential dynamic [C]choline-PET/CT pelvic scans: at baseline, after NAD and 4 months after RT-CAD. [C]Choline uptake was quantified using the average and maximum standardized uptake values at 60 min (SUV60,ave and SUV60,max), the tumour-to-muscle ratios (TMR60,max) and net irreversible retention of [C]choline at steady state (Kimod-pat).

18F-ICMT-11, a caspase-3-specific PET tracer for apoptosis: biodistribution and radiation dosimetry.

Unlabelled: Effective anticancer therapy induces tumor cell death through apoptosis. Noninvasive monitoring of apoptosis during therapy may provide predictive outcome information and help tailor treatment. A caspase-3-specific imaging radiotracer, (18)F-(S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4-difluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin ((18)F-ICMT-11), has been developed for use in PET studies.