Imaging and therapy in prostate cancer using PSMA 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. 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 radioligand therapy.

Study protocol of LANTana: a phase Ib study to investigate epigenetic modification of somatostatin receptor-2 with ASTX727 to improve therapeutic outcome with [177Lu]Lu-DOTA-TATE in patients with metastatic neuroendocrine tumours, UK.

INTRODUCTION: Suitability for peptide receptor radionuclide therapy (PRRT) for neuroendocrine neoplasia (NENs) depends on presence of somatostatin receptor-2 (SSTR2) determined by [68Ga]Ga-DOTA-peptide-positron emission tomography (PET). Some patients have low or no uptake on [68Ga]Ga-DOTA-peptide-PET, precluding PRRT. The upstream promoter region of SSRT2 is methylated, with percentage of methylation correlating with SSTR2 expression. Demethylating agents increase uptake on PET imaging in vivo such that tumours previously negative on PET become positive, correlating with a dose dependent increase in tumorous SSTR2 expression. LANTana will determine whether treatment with the demethylating agent, ASTX727, results in re-expression of SSTR2 using [68Ga]Ga-DOTA-peptide-PET to image epigenetic modification of the SSTR2 locus, allowing subsequent PRRT. METHODS AND ANALYSIS: 27 participants with a histological diagnosis of NEN (Ki67<55%) with no or low uptake on baseline [68Ga]Ga-DOTA-TATE-PET/CT will be recruited. Patients will receive 5 days of ASTX727 (fixed dose 35 mg decitabine+100 mg cedazuridine). [68Ga]Ga-DOTA-peptide-PET/CT will be repeated day 8±2; where there is significant uptake greater than liver in most lesions, PRRT will be administered. Primary objective is to determine re-expression of SSTR2 on PET imaging. Tolerability, progression-free survival, overall response and quality of life will be assessed. Methylation in peripheral blood mononuclear cells and tumorous methylation will be evaluated. ETHICS AND DISSEMINATION: LANTana has ethical approval from Leeds West Research Ethics Committee (REC Reference: 21/YH/0247).Sponsored by Imperial College London and funded by Advanced Accelerator Applications pharmaceuticals. Results will be presented at conferences and submitted to peer-reviewed journals for publication and will be available on ClinicalTrials.gov. TRIAL REGISTRATION NUMBERS: EUDRACT number: 2020-003800-15, NCT05178693.

Contemporary Multimodality Imaging of Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a disorder characterized by hypercalcemia and an elevated or inappropriately normal parathyroid hormone level. Classic features include bone pain, fractures, renal impairment, nephrolithiasis, and mental disturbance. However, most cases of PHPT are now asymptomatic at diagnosis or associated with nonspecific neurocognitive changes. The most frequent cause of PHPT is a solitary adenoma that secretes parathyroid hormone without the normal suppressive effect of serum calcium. A smaller number of cases can be attributed to multigland disease. Parathyroidectomy is curative and is considered for nearly all affected patients. Although PHPT is primarily a clinical and biochemical diagnosis, imaging is key to the localization of adenomas, which can lie in conventional locations adjacent to the thyroid gland or less commonly at ectopic sites in the neck and mediastinum. In addition, accurate localization facilitates the use of a minimally invasive or targeted surgical approach. Frequently used localization techniques include US, parathyroid scintigraphy, and four-dimensional CT. Second- and third-line modalities such as MRI, PET/CT, and selective venous sampling with or without parathyroid arteriography can increase confidence before surgery. These localization techniques, along with the associated technical aspects, relative advantages, and drawbacks, are described. Local expertise, patient factors, and surgeon preference are important considerations when determining the type and sequence of investigation. A multimodality approach is ultimately desirable, particularly in challenging scenarios such as multigland disease, localization of ectopic adenomas, and persistent or recurrent PHPT. Online supplemental material is available for this article. ©RSNA, 2022.

The associations of psoas and masseter muscles with sarcopenia and related adverse outcomes in older trauma patients: a retrospective study.

BACKGROUND: There is an emerging role for radiological evaluation of psoas muscle as a marker of sarcopenia in trauma patients. Older trauma patients are more likely to undergo cranial than abdomino-pelvic imaging. Identifying sarcopenia using masseter cross-sectional area (M-CSA) has shown correlation with mortality. We sought to determine the correlation between psoas: lumbar vertebral index (PLVI) and the M-CSA, and their association with health outcomes. METHODS: Patients aged 65 or above, who presented as a trauma call over a 1-year period were included if they underwent cranial or abdominal CT imaging. Images were retrospectively analysed to obtain PLVI and mean M-CSA measurements. Electronic records were abstracted for outcomes. Logistic regression methods, log scale analyses, Cox regression model and Kaplan-Meier plots were used to determine association of sarcopenia with outcomes. RESULTS: There were 155 eligible patients in the M-CSA group and 204 patients in the PLVI group. Sarcopenia was defined as the lowest quartile in each group. Pearson's correlation indicated a weakly positive linear relationship (r = 0.35, p < 0.001) between these. There was no statistical association between M-CSA sarcopenia status and any measured outcomes. Those with PLVI sarcopenia were more likely to die in hospital (adjusted OR 3.38, 95% CI 1.47-9.73, p = 0.006) and at 2 years (adjusted HR 1.90, 95% CI 1.11-3.25, p = 0.02). Only 29% patients with PLVI sarcopenia were discharged home, compared with 58% without sarcopenia (p = 0.001). CONCLUSION: Sarcopenia, defined by PLVI, is predictive of increased in-patient and 2-year mortality. Our study did not support prognostic relevance of M-CSA.

Treatment of Neuroendocrine Neoplasms with Radiolabeled Peptides-Where Are We Now.

Peptide receptor radionuclide therapy (PRRT) has been one of the most successful and exciting examples of theranostics in nuclear medicine in recent decades and is now firmly embedded in many treatment algorithms for unresectable or metastatic neuroendocrine neoplasms (NENs) worldwide. It is widely considered to be an effective treatment for well- or moderately differentiated neoplasms, which express high levels of somatostatin receptors that can be selectively targeted. This review article outlines the scientific basis of PRRT in treatment of NENs and describes its discovery dating back to the early 1990s. Early treatments utilizing Indium-111, a γ-emitter, showed promise in reduction in tumor size and improvement in biochemistry, but were also met with high radiation doses and myelotoxic and nephrotoxic effects. Subsequently, stable conjugation of DOTA-peptides with ß-emitting radionuclides, such as Yttrium-90 and Lutetium-177, served as a breakthrough for PRRT and studies highlighted their potential in eliciting progression-free survival and quality of life benefits. This article will also elaborate on the key trials which paved the way for its approval and will discuss therapeutic considerations, such as patient selection and administration technique, to optimize its use.

The role of amyloid PET in patient selection for extra-ventricular shunt insertion for the treatment of idiopathic normal pressure hydrocephalus: A pooled analysis.

BACKGROUND: Idiopathic Normal Pressure Hydrocephalus (iNPH) can be effectively treated through shunt insertion. However, most shunted patients experience little or no clinical benefit, which suggests suboptimal patient selection. While contentious, multiple studies have reported poorer shunt outcomes associated with concomitant Alzheimer's disease. Prompted by this observation, multiple studies have assessed the role of amyloid PET, a specific test for Alzheimer's disease, in patient selection for shunting. METHODS: A comprehensive literature search was performed to identify studies that assessed the association between amyloid PET result and the clinical response to shunting in patients with suspected iNPH. Pooled diagnostic statistics were calculated. RESULTS: Across three relevant studies, a total of 38 patients with suspected iNPH underwent amyloid PET imaging and shunt insertion. Twenty-three patients had a positive clinical response to shunting. 18/28 (64.3%) of patients with a negative amyloid PET and 5/10 (50%) with a positive amyloid PET had a positive response to shunting. The pooled sensitivity, specificity and accuracy was 33.3%, 76.2% and 58.3%. None of these statistics reached statistical significance. CONCLUSION: The results of this pooled analysis do not support the selection of patients with suspected iNPH for shunting on the basis of amyloid PET alone. However, due to small cohort sizes and weakness in study design, further high-quality studies are required to properly determine the role of amyloid PET in assessing this complex patient group.

Adnexal Torsion: Review of Radiologic Appearances.

Adnexal torsion is the twisting of the ovary, and often of the fallopian tube, on its ligamental supports, resulting in vascular compromise and ovarian infarction. The definitive management is surgical detorsion, and prompt diagnosis facilitates preservation of the ovary, which is particularly important because this condition predominantly affects premenopausal women. The majority of patients present with severe acute pain, vomiting, and a surgical abdomen, and the diagnosis is often made clinically with corroborative US. However, the symptoms of adnexal torsion can be variable and nonspecific, making an early diagnosis challenging unless this condition is clinically suspected. When adnexal torsion is not clinically suspected, CT or MRI may be performed. Imaging has an important role in identifying adnexal torsion and accelerating definitive treatment, particularly in cases in which the diagnosis is not an early consideration. Several imaging features are characteristic of adnexal torsion and can be seen to varying degrees across different modalities: a massive, edematous ovary migrated to the midline; peripherally displaced ovarian follicles resembling a string of pearls; a benign ovarian lesion acting as a lead mass; surrounding inflammatory change or free fluid; and the uterus pulled toward the side of the affected ovary. Hemorrhage and absence of internal flow or enhancement are suggestive of ovarian infarction. Pertinent conditions to consider in the differential diagnosis are a ruptured hemorrhagic ovarian cyst, massive ovarian edema, ovarian hyperstimulation, and a degenerating leiomyoma. Online supplemental material is available for this article. ©RSNA, 2021.

The Utility of Psoas Muscle Assessment in Predicting Frailty in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: The rise in an ageing population has resulted in an increase in the prevalence of aortic stenosis. With the advent and rapid expansion in the use of transcatheter aortic valve replacements (TAVRs), patients with severe aortic stenosis, traditionally thought too high risk for surgical intervention, are now being treated with generally favourable results. Frailty is an important factor in determining outcome after a TAVR, and an assessment of frailty is fundamental in the identification of appropriate patients to treat. OBJECTIVE: The objective of the study was to identify if the psoas muscle area is associated with frailty in TAVR patients and outcome after intervention. METHOD: In this prospective study, we measured outcomes of 62 patients who underwent TAVR procedures against the psoas muscle area and the Reported Edmonton Frail Scale (REFS). Our aim was to assess if psoas muscle assessment can be used as a simple method to predict frailty in our population group. RESULTS: A total of 60 patients met the study criteria. Mean psoas-lumbar vertebral index was 0.61, with a lower value in the frail group. There was not a statistically significant correlation between the psoas measures, REFS score (indicative of frailty), and mortality. However, there was a statistically significant relationship between the psoas size and REFS score (p=0.043). CONCLUSION: Psoas assessment can be useful in providing additional information when planning for patients to undergo a TAVR and can be used as a screening tool to help identify frail patients within this high-risk group.

Ethnic variability in body size, proportions and composition in children aged 5 to 11 years: is ethnic-specific calibration of bioelectrical impedance required?

BACKGROUND: Bioelectrical Impedance Analysis (BIA) has the potential to be used widely as a method of assessing body fatness and composition, both in clinical and community settings. BIA provides bioelectrical properties, such as whole-body impedance which ideally needs to be calibrated against a gold-standard method in order to provide accurate estimates of fat-free mass. UK studies in older children and adolescents have shown that, when used in multi-ethnic populations, calibration equations need to include ethnic-specific terms, but whether this holds true for younger children remains to be elucidated. The aims of this study were to examine ethnic differences in body size, proportions and composition in children aged 5 to 11 years, and to establish the extent to which such differences could influence BIA calibration. METHODS: In a multi-ethnic population of 2171 London primary school-children (47% boys; 34% White, 29% Black African/Caribbean, 25% South Asian, 12% Other) detailed anthropometric measurements were performed and ethnic differences in body size and proportion were assessed. Ethnic differences in fat-free mass, derived by deuterium dilution, were further evaluated in a subsample of the population (n = 698). Multiple linear regression models were used to calibrate BIA against deuterium dilution. RESULTS: In children < 11 years of age, Black African/Caribbean children were significantly taller, heavier and had larger body size than children of other ethnicities. They also had larger waist and limb girths and relatively longer legs. Despite these differences, ethnic-specific terms did not contribute significantly to the BIA calibration equation (Fat-free mass = 1.12+0.71*(height2/impedance)+0.18*weight). CONCLUSION: Although clear ethnic differences in body size, proportions and composition were evident in this population of young children aged 5 to 11 years, an ethnic-specific BIA calibration equation was not required.