Prostate-Specific Membrane Antigen-Positron Emission Tomography-Guided Radiomics and Machine Learning in Prostate Carcinoma.

Positron emission tomography (PET) using radiolabeled prostate-specific membrane antigen targeting PET-imaging agents has been increasingly used over the past decade for imaging and directing prostate carcinoma treatment. Here, we summarize the available literature data on radiomics and machine learning using these imaging agents in prostate carcinoma. Gleason scores derived from biopsy and after resection are discordant in a large number of prostate carcinoma patients.

Prostate-Specific Membrane Antigen Biology and Pathophysiology in Prostate Carcinoma, an Update: Potential Implications for Targeted Imaging and Therapy.

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, was shown to be expressed 100-1000 fold higher in prostate adenocarcinoma as compared to normal prostate epithelium. Given the enzymatic function of PSMA with the presence of an internalization triggering motif, various Glu-urea-Lys-based inhibitors have been developed and, amongst others, radiolabeled with positron emitters for targeted positron emission tomography imaging such as Ga-PSMA-HBED-CC Glu-urea-Lys(Ahx) as well as with beta and alpha-emitting radioisotopes for targeted therapy, e.g.

Principal Component Analysis Applied to Radiomics Data: Added Value for Separating Benign from Malignant Solitary Pulmonary Nodules.

Here, we report on the added value of principal component analysis applied to a dataset of texture features derived from 39 solitary pulmonary lung nodule (SPN) lesions for the purpose of differentiating benign from malignant lesions, as compared to the use of SUVmax alone. Texture features were derived using the LIFEx software. The eight best-performing first-, second-, and higher-order features for separating benign from malignant nodules, in addition to SUVmax (MaximumGreyLevelSUVbwIBSI184IY), were included for PCA.

Correlation between [Ga]Ga-FAPI-46 PET Imaging and HIF-1α Immunohistochemical Analysis in Cervical Cancer: Proof-of-Concept.

Hypoxia leads to changes in tumor microenvironment (upregulated CAFs) with resultant aggressiveness. A key factor in the physiological response to hypoxia is hypoxia-inducible factor-1alpha (HIF-1α). [Ga]Ga-FAPI PET imaging has been demonstrated in various cancer types.

Ac-PSMA-617 radioligand therapy of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC): preliminary clinical findings.

Purpose: Ac-PSMA-617 has demonstrated good anti-tumor effect as a treatment option for metastatic castration-resistant prostate cancer (mCRPC) patients. No study has previously assessed treatment outcome and survival following Ac-PSMA-617 treatment of de novo metastatic hormone-sensitive prostate carcinoma (mHSPC) patients. Based on the potential side effects that are known and explained to the patients by the oncologist, some of the patients refused the standard treatment and are seeking alternative therapies.

Principal component analysis of texture features derived from FDG PET images of melanoma lesions.

Background: The clinical utility of radiomics is hampered by a high correlation between the large number of features analysed which may result in the "bouncing beta" phenomenon which could in part explain why in a similar patient population texture features identified and/or cut-off values of prognostic significance differ from one study to another. Principal component analysis (PCA) is a technique for reducing the dimensionality of large datasets containing highly correlated variables, such as texture feature datasets derived from FDG PET images, increasing data interpretability whilst at the same time minimizing information loss by creating new uncorrelated variables that successively maximize variance. Here, we report on PCA of a texture feature dataset derived from 123 malignant melanoma lesions with a significant range in lesion size using the freely available LIFEx software.

The quorum sensing peptide EntF* promotes colorectal cancer metastasis in mice: a new factor in the host-microbiome interaction.

Background: Colorectal cancer, one of the most common malignancies worldwide, is associated with a high mortality rate, mainly caused by metastasis. Comparative metagenome-wide association analyses of healthy individuals and cancer patients suggest a role for the human intestinal microbiota in tumor progression. However, the microbial molecules involved in host-microbe communication are largely unknown, with current studies mainly focusing on short-chain fatty acids and amino acid metabolites as potential mediators.

Ga-PSMA-11 PET/CT Initial Staging in Black and White South African Males with ISUP Grade Group 1 and 2 Prostate Adenocarcinoma.

Prostate adenocarcinoma (PCa) is a leading cause of mortality. Black males with high-risk PCa have a poorer prognosis compared to white males. Patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 and 2 PCa have little potential for metastases post radical prostatectomy.

The Diagnostic Performance of 18F-PSMA-1007 PET/CT in Prostate Cancer Patients with Early Recurrence after Definitive Therapy with a PSA <10 ng/ml.

Aim: The prostate bed is one of the common sites of early recurrence of prostate cancer. The currently used PSMA ligands (Ga-PSMA-11 and Tc-PSMA) undergo early urinary clearance resulting in interfering physiological activity within and surrounding the prostate. This can result in sites of cancer recurrence being obscured.

A Prospective Investigation of Tumor Hypoxia Imaging with Ga-Nitroimidazole PET/CT in Patients with Carcinoma of the Cervix Uteri and Comparison with F-FDG PET/CT: Correlation with Immunohistochemistry.

Hypoxia in cervical cancer has been associated with a poor prognosis. Over the years Ga labelled nitroimidazoles have been studied and have shown improved kinetics. We present our initial experience of hypoxia Positron Emission Tomography (PET) imaging in cervical cancer with Ga-Nitroimidazole derivative and the correlation with F-FDG PET/CT and immunohistochemistry.

The Utility of Metabolic Parameters on Baseline F-18 FDG PET/CT in Predicting Treatment Response and Survival in Paediatric and Adolescent Hodgkin Lymphoma.

Lymphoma is the third most common paediatric cancer. Early detection of high-risk patients is necessary to anticipate those who require intensive therapy and follow-up. Current literature shows that residual tumor avidity on PET (Positron Emission Tomography) following chemotherapy corresponds with decreased survival.

Practical Considerations When Interpreting FDG PET/CT Imaging for Staging and Treatment Response Assessment in Melanoma Patients.

While FDG PET/CT bears a high sensitivity and specificity for the staging of stage III and IV melanoma as well as for the purpose of melanoma recurrence detection, overall results tend to vary from one part of the body to another as well as for melanoma from cutaneous or choroidal origin. In this paper, organ or site-related differences in sensitivity and specificity in melanoma patients, both from cutaneous and choroidal origin, as well as their impact on clinical decision making are discussed. Furthermore, with the advent of immunotherapy for the treatment of malignant melanoma, post-treatment related potential false positive findings have emerged, the knowledge of which is essential for accurate treatment response assessment.

Statin Intake and All-Cause Mortality among Older Nursing Home Residents.

Background: Statins are progressively accepted as being associated with reduced mortality. However, few real-world statin studies have been conducted on statin use in older people and especially the most frail, that is, the nursing home residents.

Objective: The aim of this study was to evaluate the impact of statin intake in nursing home residents on all-cause mortality.

Apoptosis Imaging in Oncology by Means of Positron Emission Tomography: A Review.

To date, a wide variety of potential PET-apoptosis imaging radiopharmaceuticals targeting apoptosis-induced cell membrane asymmetry and acidification, as well as caspase 3 activation (substrates and inhibitors) have been developed with the purpose of rapidly assessing the response to treatment in cancer patients. Many of these probes were shown to specifically bind to their apoptotic target in vitro and their uptake to be enhanced in the in vivo-xenografted tumours in mice treated by means of chemotherapy, however, to a significantly variable degree. This may, in part, relate to the tumour model used given the fact that different tumour cell lines bear a different sensitivity to a similar chemotherapeutic agent, to differences in the chemotherapeutic concentration and exposure time, as well as to the different timing of imaging performed post-treatment.

Characterization of FDG PET Images Using Texture Analysis in Tumors of the Gastro-Intestinal Tract: A Review.

Radiomics or textural feature extraction obtained from positron emission tomography (PET) images through complex mathematical models of the spatial relationship between multiple image voxels is currently emerging as a new tool for assessing intra-tumoral heterogeneity in medical imaging. In this paper, available literature on texture analysis using FDG PET imaging in patients suffering from tumors of the gastro-intestinal tract is reviewed. While texture analysis of FDG PET images appears clinically promising, due to the lack of technical specifications, a large variability in the implemented methodology used for texture analysis and lack of statistical robustness, at present, no firm conclusions can be drawn regarding the predictive or prognostic value of FDG PET texture analysis derived indices in patients suffering from gastro-enterologic tumors.

The Effects of ARBs, ACEis, and Statins on Clinical Outcomes of COVID-19 Infection Among Nursing Home Residents.

Objectives: Angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), and HMG-CoA reductase inhibitors ("statins") have been hypothesized to affect COVID-19 severity. However, up to now, no studies investigating this association have been conducted in the most vulnerable and affected population groups (ie, older adults residing in nursing homes). The objective of this study was to explore the association of ACEi/ARB and/or statins with clinical manifestations in COVID-19-infected older adults residing in nursing homes.

PSMA expression on neovasculature of solid tumors.

The use of prostate specific membrane antigen (PSMA) binding agents, labelled with diagnostic and therapeutic radio-isotopes is opening the potential for a new era of personalized management of prostate carcinoma. A wide variety of immunohistochemistry studies have shown PSMA also to be upregulated on the endothelial cells of the neovasculature of a wide variety of other solid tumors where it may facilitate endothelial cell sprouting and invasion through its regulation of lytic proteases that have the ability to cleave the extracellular matrix. Similar to the introduction of PSMA-targeting theranostics in prostate carcinoma, overexpression of PSMA on newly formed tumor vessels may serve as a target for imaging and subsequent treatment of cancer through the use of agents that are capable of blocking PSMA in its function or through PSMA-mediated delivery of chemotherapeutics or radiation agents.

PSMA-Targeting Positron Emission Agents for Imaging Solid Tumors Other Than Non-Prostate Carcinoma: A Systematic Review.

Despite its name, prostate-specific membrane antigen (PSMA) has been shown using immunohistochemistry (IHC) to also be over-expressed in the tumor neovasculature of a wide variety of solid tumors other than prostate carcinoma. Accordingly, positron-emitting radiolabeled small molecules targeting PSMA, initially developed for positron emission tomography in prostate carcinomas, are currently being explored for their staging and restaging potential as an alternative imaging modality in other solid tumor types where 18-F-fluorodeoxyglucose (FDG)-PET imaging has low diagnostic accuracy. In this paper, the currently available literature in this field is reviewed.

Predictors of Overall and Disease-Free Survival in Metastatic Castration-Resistant Prostate Cancer Patients Receiving Ac-PSMA-617 Radioligand Therapy.

Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with Ac-PSMA-617, identifying variables predictive for overall survival (OS) and progression-free survival (PFS) after Ac-PSMA-617 treatment. Ac-PSMA-617 was administered to patients who had metastatic castration-resistant prostate carcinoma and who had exhausted available therapy options for their disease.

18F-FDG-PET/CT imaging of uterine cervical cancer recurrence in women with and without HIV infection.

Background: To compare the rate, time and, pattern of recurrence of cervical cancer between patients with and without HIV infection and to determine factors predicting cervical cancer recurrence in patients evaluated by F-FDG-PET/CT.

Methods: We reviewed the F-FDG-PET/CT images of patients with histologically proven cervical carcinoma who were presenting with suspected recurrence. We extracted epidemiologic data, previous treatment, histologic subtype, HIV status, viral load and CD4 counts from the electronic laboratory database and the referral form for the F-FDG-PET/CT study.

Impact of PET reconstruction protocols on quantification of lesions that fulfil the PERCIST lesion inclusion criteria.

Background: The aim of this study was to compare liver and oncologic lesion standardized uptake values (SUV) obtained through two different reconstruction protocols, GE's newest clinical lesion detection protocol (Q.Clear) and the EANM Research Ltd (EARL) harmonization protocol, and to assess the clinical relevance of potential differences and possible implications for daily clinical practice using the PERCIST lesional inclusion criteria. NEMA phantom recovery coefficients (RC) and SUV normalized for lean body mass (LBM), referred to as SUV normalized for LBM (SUL), of liver and lesion volumes of interest were compared between the two reconstruction protocols.

Prognostic Value of Pre-treatment F-18 FDG PET Metabolic Metrics in Patients with Locally Advanced Carcinoma of the Anus with and without HIV Infection.

Aim: To investigate the prognostic value of F-18 FDG PET metabolic parameters in patients with anal carcinoma with and without human immunodeficiency virus infection (HIV).

Methods: Maximum standardized uptake value (SUV), mean standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were obtained on F-18 FDG PET/CT images of treatment-naïve patients with locally advanced anal squamous cell carcinoma (ASSC). We compared patients' characteristics and F-18 FDG PET metabolic metrics between the HIV-infected patients and the HIV-uninfected patients.

Ga-PSMA PET/CT Replacing Bone Scan in the Initial Staging of Skeletal Metastasis in Prostate Cancer: A Fait Accompli?

Purpose: Ga ligands targeting prostate-specific membrane antigen (PSMA) are rapidly emerging as a significant step forward in the management of prostate cancer. PSMA is a type II transmembrane protein with high expression in prostate carcinoma cells. We prospectively evaluated the use of Ga-PSMA positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer and compared the results to those for technetium-99m (Tc)-10-metacyloyloxydecyl dihydrogen phosphate (MDP) bone scintigraphy (BS).

Blood-brain barrier transport kinetics of NOTA-modified proteins: the somatropin case.

Background: Chemical modifications such as PEG, polyamine and radiolabeling on proteins can alter their pharmacokinetic behavior and their blood-brain barrier (BBB) transport characteristics. NOTA, i.e.