The Impact of Baseline PSMA PET/CT Versus CT on Outcomes of 223Ra Therapy in Metastatic Castration-Resistant Prostate Cancer Patients.

Imaging before 223Ra-dichloride (223Ra) 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 223Ra therapy. Methods: A secondary analysis of the data of a prospective observational study (NCT04995614) was performed. Patients received a maximum of 6 223Ra cycles and were retrospectively divided into the bPSMA or baseline CT (bCT) groups. All patients received baseline bone scintigraphy. Primary endpoints were alkaline phosphatase and prostate-specific antigen response. Secondary endpoints were overall survival (OS) and radiologic response. Results: Between 2017 and 2020, 122 mCRPC patients were included: 18 (14.8%) in the bPSMA group and 104 (85.2%) in the bCT group. All baseline characteristics were comparable. No significant differences in alkaline phosphatase or prostate-specific antigen response were found. The bCT group showed an OS significantly shorter than that of the bPSMA group (12.4 vs. 19.9 mo, P = 0.038). In 31 of 76 patients (40.1%) in the bCT group who also received posttherapy CT, lymph node or visceral metastases (soft-tissue involvement [STI]) were detected after 223Ra therapy, compared with 0 of 15 patients in the bPSMA group who received posttherapy PSMA PET/CT or CT. No significant difference in OS was found between patients in the bCT or posttherapy CT subgroup without STI (46/76) and the bPSMA group. Conclusion: bPSMA versus CT does not seem to impact biochemical response during 223Ra therapy in mCRPC patients. Nevertheless, patients in the bCT group had a significantly shorter OS, most likely due to underdetection of STI in this group. Therefore, replacing bCT with PSMA PET/CT appears to be a valuable screening method for identifying patients who will benefit most from 223Ra therapy.

Quantitative CT Evaluation of Bone Mineral Density in the Thoracic Spine on 18F-Fluorocholine PET/CT Imaging in Patients With Primary Hyperparathyroidism.

INTRODUCTION: Measurement of bone mineral density (BMD) with quantitative CT (QCT) carries several advantages over other densitometric techniques, including superior assessment of the spine. As most QCT studies evaluated the lumbar spine, measurements of the thoracic spine are limited. We performed QCT analysis of the thoracic spine in a cohort of patients with primary hyperparathyroidism. MATERIALS AND METHODS: This study was a retrospective QCT analysis of the thoracic spine on 18F-fluorocholine PET/CT scans in patients with primary hyperparathyroidism patients between March 2018 and December 2022. Correlations between QCT-derived BMD or Hounsfield units (HU) and demographic data, laboratory parameters, results from histopathological examination after parathyroidectomy and results of DXA imaging were analyzed, when available. RESULTS: In 189 patients, mean QCT-derived BMD at the thoracic spine was 85.6 mg/cm3. Results from recent DXA were available in 122 patients. Mean thoracic QCT-derived BMD and HU were significantly correlated with DXA-derived BMD in lumbar spine, total hip and femoral neck and with the lowest T-score at DXA imaging. Only weak correlations were found with BMI or 18F-fluorocholine uptake, while no significant correlations were found with adenoma weight, PTH or calcium levels. CONCLUSION: Our study confirms correlation between QCT-derived BMD in the thoracic spine with age and DXA-derived BMD measurements within a population of patients with primary hyperparathyroidism. Establishment of reference BMD values for individual thoracic vertebrae, may allow direct osteoporosis classification on thoracic CT imaging.

Feasibility of Left Ventricle Ejection Fraction Calculation Using Electrocardiographically Gated SPECT Acquisition of 99m Tc-HDP Bone Scintigraphy in Cardiac Amyloidosis.

ABSTRACT: We performed bone scintigraphy in 6 patients with suspected cardiac amyloidosis. To evaluate feasibility of left ventricle function analysis, we additionally performed electrocardiographically gated SPECT acquisition. The cardiac-gated SPECT data confirmed adequate tracer uptake for automatic myocardial contour determination. LVEF estimations ranged between 24% and 54%. Comparison with LVEF estimations from prior echocardiography generally showed only small differences. In one patient, the LVEF measurements from both methods seemed discordant, probably reflecting actual LVEF worsening, which was confirmed at follow-up echocardiography. Therefore, our results may suggest that cardiac-gated SPECT acquisition at bone scintigraphy can provide meaningful estimates of LVEF.

Clinical Pharmacology of Radiotheranostics in Oncology.

The combined use of diagnostic and therapeutic radioligands with the same molecular target, also known as theranostics, enables accurate patient selection, targeted therapy, and prediction of treatment response. Radioiodine, bone-seeking radioligands and norepinephrine analogs have been used for many years for diagnostic imaging and radioligand therapy of thyroid carcinoma, bone metastases, pheochromocytoma, paraganglioma, and neuroblastoma, respectively. In recent years, radiolabeled somatostatin analogs and prostate-specific membrane antigen ligands have shown clinical efficacy in the treatment of neuroendocrine tumors and prostate cancer, respectively. Several candidate compounds are targeting novel theranostic targets such as fibroblast activation protein, C-X-C chemokine receptor 4, and gastrin-releasing peptide receptor. In addition, several strategies to improve efficacy of radioligand therapy are being evaluated, including dosimetry-based dose optimization, multireceptor targeting, upregulation of target receptors, radiosensitization, pharmacogenomics, and radiation genomics. Design and evaluation of novel radioligands and optimization of dose and dose schedules, within the complex context of individualized multimodal cancer treatment, requires a multidisciplinary approach that includes clinical pharmacology. Significant increases in the use of these radiopharmaceuticals in routine oncological practice can be expected, which will have major impact on patient care as well as (radio)pharmacy utilization.

Peripheral Photopenia on Whole-Body PET/CT Imaging With 18F-FDG in Patients With Compartment Syndrome and Mesenteric Venous Thrombosis.

We present 2 cases that demonstrate photopenia in peripheral areas on whole-body PET/CT imaging with F-FDG as a sign of absent perfusion with severe short-term complications. The scan of the first patient shows photopenia in the right ankle and foot, resulting from compartment syndrome, caused by hemolytic group A streptococcus bacteremia with endocarditis and septic emboli, necessitating lower leg amputation. The scan of the second patient shows photopenia in the transverse colon, resulting from mesenteric venous thrombosis caused by polycythemia vera, leading to necrosis and perforation of the transverse colon, necessitating transverse and right hemicolectomy.

Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury.

Rubrospinal neurons (RSNs) undergo marked atrophy after cervical axotomy. This progressive atrophy may impair the regenerative capacity of RSNs in response to repair strategies that are targeted to promote rubrospinal tract regeneration. Here, we investigated whether we could achieve long-term rescue of RSNs from lesion-induced atrophy by adeno-associated viral (AAV) vector-mediated gene transfer of brain-derived neurotrophic factor (BDNF). We show for the first time that AAV vectors can be used for the persistent transduction of highly atrophic neurons in the red nucleus (RN) for up to 18 months after injury. Furthermore, BDNF gene transfer into the RN following spinal axotomy resulted in counteraction of atrophy in both the acute and chronic stage after injury. These novel findings demonstrate that a gene therapeutic approach can be used to reverse atrophy of lesioned CNS neurons for an extended period of time.