Systematic Review of the First 40 Cases of 177Lu-PSMA Therapy in the Treatment of Non-prostatic Cancer.

BACKGROUND/AIM: The current systematic review aimed to collect and analyze all available published and unpublished cases in which prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (177Lu-PSMA) was used to treat non-prostatic cancer. MATERIALS AND METHODS: Literature search and evidence acquisition through contacts with organizations that use 177Lu-PSMA were employed. PubMed/Medline, SCOPUS, and ScienceDirect searches were performed following PRISMA recommendations. The search strategy was to screen all articles describing 177Lu-PSMA radioligand therapy published to date with the key word "177Lu-PSMA". These articles were collected and screened for non-prostatic cancer cases. Quality assessment was performed using the GRADE criteria. RESULTS: A total of 713 articles were screened, and the search revealed 15 eligible records. Forty patients with a mean age of 51.2±18.5 years were treated with 177Lu-PSMA for non-prostatic cancer. Of them, 30 cases were published, and 10 were found in medical institution records. Cancers of the salivary glands were most often targeted (13/40), followed by various brain cancer types (8/40), and osteosarcoma (6/40). The authors used previously established protocols for castration-resistant prostate cancer with the dose per cycle as 6.0-7.4 GBq and the number of cycles between one and four. Toxicity was estimated as low, and 21 out of 28 patients with reported outcomes survived to the time of the publication. CONCLUSION: PSMA-targeted radioligand therapy was infrequently used to treat different non-prostatic cancer types in various target organs. These pioneering efforts indicate that 177Lu-PSMA can be used to treat non-prostatic cancer with PSMA expression. The toxicity of such treatment was low, and the outcome was relatively good.

Nuclear imaging in Parkinson's disease: The past, the present, and the future.

The current review analyzed Parkinson's disease-related (PD) literature published from 1817 to 2021 and specifically concentrated on imaging-related works published from the 1960s to 2021. We analyzed the history of PD-related imaging development, its current condition, and pointed out some understudied aspects to be investigated in the future. The present review is specifically concentrated on nuclear imaging techniques. The available imaging armamentarium for PD investigation is very broad, variable, and diversified and includes structural, diffusion-weighted and diffusion tensor, resting-state, and task-based functional MRI, proton magnetic resonance spectroscopy, transcranial B-mode sonography, single-photon emission CT (SPECT), and positron emission tomography (PET). Specifically, PET is a reliable tool for quantifying nigrostriatal functions, glucose metabolism, amyloid, tau, and α-synuclein molecular imaging, as well as neuroinflammation. Besides 18F-DOPA and 18F-FDG, PET and SPECT use various other radiopharmaceuticals. Also, some studies have demonstrated that myocardial 123I-MIBG scintigraphy can be useful for the early differential diagnosis of patients with PD from other atypical PD. However, in addition to further perfecting of differential diagnosis imaging tools, some aspects of etiology (PD genetics), pathology (the pons and medulla), pathophysiology (neuroinflammation), and early diagnosis of PD remain understudied. The currently available set of neuroimaging tools can provide adequate imaging data for early diagnosis, differential diagnosis, progression assessment, and treatment assessment of PD. To adjust this armamentarium to routine clinical needs, there is an urgent need for the generally accepted protocol for PD-related imaging investigations. Closer cooperation and data exchange between radiologists and pathologists are desirable.

Pressure pulsations enhance penetration index in COPD.

This study was done in order to evaluate the effect of a novel pressure pulsation device (Pulsehaler™, Respinova Ltd., Israel) on the deposition pattern of inhaled aerosol in the lungs of COPD patients. Fifteen COPD patients were recruited to undergo spirometry and SPECT-CT lung scan following nebulization of radioactively labeled albuterol in saline solution with a jet nebulizer ("NEB") and with a combined Pulsehaler™/jet nebulizer ("PH + NEB") treatment. Central and peripheral segments of the coronal and transverse SPECT scans were evaluated for total counts and for the ratios between peripheral counts and central counts (penetration Index, "PI"). There was a significant improvement in FEV1 from before to after albuterol treatment in the PH + NEB group (151 ml ± 187, p < 0.008), but not in the NEB only group (66 ml ± 125, p = 0.06). FVC, FEF25-75, FEV1%, FVC%, FEF25, FEF50, and FEF75 also improved significantly in the PH + NEB group but not the NEB group. There were significant improvements seen between treatments for FEF25-75 (PH + NEB > NEB, p = 0.0176), FEF75 (PH + NEB > NEB, p = 0.0028), but not for the other spirometry measures. Borg scores also were improved significantly improved in PH + NEB vs NEB (p = 0.0006). Total lung deposition and total body deposition were lower in the PH + NEB treatments vs the NEB treatments. However, PI values were 3.08 ± 0.67 times greater on average with the PH + NEB (p = 0.026) as compared to NEB only. The magnitude of the increased penetration index observed in this study indicates that pressure pulsations should be further explored as means to improve drug delivery into the distal small airways of the bronchial tree. Effects of the pressure pulsations on small airway patency could be the mechanism by which the effect was achieved.

Abundance of P-glycoprotein and Breast Cancer Resistance Protein Measured by Targeted Proteomics in Human Epileptogenic Brain Tissue.

Our goal was to measure the absolute differential abundance of key drug transporters in human epileptogenic brain tissue and to compare them between patients and at various distances from the epileptogenic zone within the same patient. Transporter protein abundance was quantified in brain tissue homogenates from patients who underwent epilepsy surgery, using targeted proteomics, and correlations with clinical and tissue characteristics were assessed. Fourteen brain samples (including four epileptogenic hippocampal samples) were collected from nine patients. Among the quantifiable drug transporters, the abundance (median, range) ranked: breast cancer resistance protein (ABCG2/BCRP; 0.55, 0.01-3.26 pmol/g tissue) > P-glycoprotein (ABCB1/MDR1; 0.30, 0.02-1.15 pmol/g tissue) > equilibrative nucleoside transporter 1 (SLC29A1/ENT1; 0.06, 0.001-0.35 pmol/g tissue). The ABCB1/ABCG2 ratio (mean 0.27, range 0.08-0.47) was comparable with literature values from nonepileptogenic brain tissue (mean 0.5-0.8). Transporter abundance was lower in the hippocampi than in the less epileptogenic neocortex of the same patients. ABCG2/BCRP and ABCB1/MDR1 expression strongly correlated with that of glucose transporter 1 (SLC2A1/GLUT1) (r = 0.97, p < 0.001; r = 0.90, p < 0.01, respectively). Low transporter abundance was found in patients with overt vascular pathology, whereas the highest abundance was seen in a sample with normally appearing blood vessels. In conclusion, drug transporter abundance highly varies across patients and between epileptogenic and less epileptogenic brain tissue of the same patient. The strong correlation in abundance of ABCB1/MDR1, ABCG2/BCRP, and SLC2A1/GLUT1 suggests variation in the content of the functional vasculature within the tissue samples. The epileptogenic tissue can be depleted of key drug transport mechanisms, warranting consideration when selecting treatments for patients with drug-resistant epilepsy.

Imaging-based predictors for hyperbaric oxygen therapy outcome in post-stroke patients. Report 1.

We tested the hypothesis that if SPECT/CT-detected volumes of active and inactive parts of brain tissue present correlation with the results of hyperbaric oxygen therapy (HBOT) of ischemic stroke, SPECT imaging may serve as a selective tool for post-stroke patients to indicate cases that may significantly benefit from HBOT. A retrospective analysis was conducted on 62 consecutive patients administered for HBOT after the ischemic stroke episode. All patients received 60 daily hyperbaric sessions consisting of 90 min of exposure to 100% oxygen at a pressure of 0.2 MPa. The results of the treatment were assessed in correlation with SPECT/CT-detected changes of volumes of the penumbra area around the stroke zone. Patients who significantly benefitted from HBOT (n = 24) by an improvement of their clinical neurologic status and quality of life had the large penumbra zone (363 ± 20.5 ml) that was significantly diminished during HBOT. Patients who did not benefit from HBOT (n = 20) had a relatively small volume of the penumbra zone (148 ± 29.3 ml) and its further diminishing during HBOT was insignificant. The HBOT results were unclear in 18 patients with penumbra volumes between these values. These findings support our hypothesis that the large volume of the penumbra area around the stroke zone can serve as a significant predictor for positive clinical outcome following HBOT in post-stroke patients. The SPECT/CT-based assessment procedure of the volume of the penumbra may serve as an effective selecting tool when HBOT is administered for patients with ischemic stroke.

Low-radiation of technetium-99m-sestamibi and single-photon emission computed tomography/computed tomography to diagnose parathyroid lesions.

We compared preoperative regular activity and low-activity radiology-based predictions with real surgical and pathological findings for parathyroidectomy surgery. The study retrospectively analyzed 54 consecutive cases (2009-2016) for benign tumor removal. Technetium-99m (Tc-99m)-sestamibi was used as a diagnostic radiopharmaceutical for diagnostic dual-phase parathyroid scintigraphy and single-photon emission computed tomography/computed tomography. We assessed images obtained with the radiation activity of 925 megabecquerel (MBq) and images obtained with the activity of 185 MBq. The study compared preoperative evaluation of tumor presence, multiplicity, location, and the type of pathology with actual data that were revealed during the operation and pathological investigation. The agreement between preoperative radiological prediction and actual location, number, and type of the parathyroid lesions was achieved in 98.4% (n = 61/62 lesions). The agreement between 925 MBq-based and 185-MBq based investigations was 100%. The agreement between radiological and pathological findings was 100% for both investigations. Our data suggest that the radioactivity of 185 MBq applied in the evaluation of the parathyroid glands provides results similar to the currently used 925-1110 MBq if used for diagnostic dual-phase parathyroid scintigraphy with Tc-99m-sestamibi. Such radioactivity may reduce the exposure to radiation of the patients and the staff without compromising results of the investigation.

Hyperbaric oxygen therapy can diminish fibromyalgia syndrome--prospective clinical trial.

BACKGROUND: Fibromyalgia Syndrome (FMS) is a persistent and debilitating disorder estimated to impair the quality of life of 2-4% of the population, with 9:1 female-to-male incidence ratio. FMS is an important representative example of central nervous system sensitization and is associated with abnormal brain activity. Key symptoms include chronic widespread pain, allodynia and diffuse tenderness, along with fatigue and sleep disturbance. The syndrome is still elusive and refractory. The goal of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on symptoms and brain activity in FMS. METHODS AND FINDINGS: A prospective, active control, crossover clinical trial. Patients were randomly assigned to treated and crossover groups: The treated group patients were evaluated at baseline and after HBOT. Patients in the crossover-control group were evaluated three times: baseline, after a control period of no treatment, and after HBOT. Evaluations consisted of physical examination, including tender point count and pain threshold, extensive evaluation of quality of life, and single photon emission computed tomography (SPECT) imaging for evaluation of brain activity. The HBOT protocol comprised 40 sessions, 5 days/week, 90 minutes, 100% oxygen at 2ATA. Sixty female patients were included, aged 21-67 years and diagnosed with FMS at least 2 years earlier. HBOT in both groups led to significant amelioration of all FMS symptoms, with significant improvement in life quality. Analysis of SPECT imaging revealed rectification of the abnormal brain activity: decrease of the hyperactivity mainly in the posterior region and elevation of the reduced activity mainly in frontal areas. No improvement in any of the parameters was observed following the control period. CONCLUSIONS: The study provides evidence that HBOT can improve the symptoms and life quality of FMS patients. Moreover, it shows that HBOT can induce neuroplasticity and significantly rectify abnormal brain activity in pain related areas of FMS patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01827683.

Improvement of memory impairments in poststroke patients by hyperbaric oxygen therapy.

OBJECTIVE: Several recent studies have shown that hyperbaric oxygen (HBO2) therapy carry cognitive and motor therapeutic effects for patients with acquired brain injuries. The goal of this study was to address the specific effects of HBO2 on memory impairments after stroke at late chronic stages. METHOD: A retrospective analysis was conducted on data of 91 stroke patients 18 years or older (mean age ∼60 years) who had either ischemic or hemorrhagic stroke 3-180 months before HBO2 therapy (M = 30-35 months). The HBO2 protocol included 40 to 60 daily sessions, 5 days per week, 90 min each, 100% oxygen at 2ATA, and memory tests were administered before and after HBO2 therapy using NeuroTrax's computerized testing battery. Assessments were based on verbal or nonverbal, immediate or delayed memory measures. The cognitive tests were compared with changes in the brain metabolic state measured by single-photon emission computed tomography. RESULTS: Results revealed statistically significant improvements (p < .0005, effect sizes medium to large) in all memory measures after HBO2 treatments. The clinical improvements were well correlated with improvement in brain metabolism, mainly in temporal areas. CONCLUSIONS: Although further research is needed, the results illustrate the potential of HBO2 for improving memory impairments in poststroke patients, even years after the acute event.

Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury - randomized prospective trial.

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of death and disability in the US. Approximately 70-90% of the TBI cases are classified as mild, and up to 25% of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging. The current study tested the effectiveness of Hyperbaric Oxygen Therapy (HBOT) in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments. METHODS AND FINDINGS: The trial population included 56 mTBI patients 1-5 years after injury with prolonged post-concussion syndrome (PCS). The HBOT effect was evaluated by means of prospective, randomized, crossover controlled trial: the patients were randomly assigned to treated or crossover groups. Patients in the treated group were evaluated at baseline and following 40 HBOT sessions; patients in the crossover group were evaluated three times: at baseline, following a 2-month control period of no treatment, and following subsequent 2-months of 40 HBOT sessions. The HBOT protocol included 40 treatment sessions (5 days/week), 60 minutes each, with 100% oxygen at 1.5 ATA. "Mindstreams" was used for cognitive evaluations, quality of life (QOL) was evaluated by the EQ-5D, and changes in brain activity were assessed by SPECT imaging. Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period. SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements. CONCLUSIONS: HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage. TRIAL REGISTRATION: ClinicalTrials.gov NCT00715052.

Hyperbaric oxygen induces late neuroplasticity in post stroke patients--randomized, prospective trial.

BACKGROUND: Recovery after stroke correlates with non-active (stunned) brain regions, which may persist for years. The current study aimed to evaluate whether increasing the level of dissolved oxygen by Hyperbaric Oxygen Therapy (HBOT) could activate neuroplasticity in patients with chronic neurologic deficiencies due to stroke. METHODS AND FINDINGS: A prospective, randomized, controlled trial including 74 patients (15 were excluded). All participants suffered a stroke 6-36 months prior to inclusion and had at least one motor dysfunction. After inclusion, patients were randomly assigned to "treated" or "cross" groups. Brain activity was assessed by SPECT imaging; neurologic functions were evaluated by NIHSS, ADL, and life quality. Patients in the treated group were evaluated twice: at baseline and after 40 HBOT sessions. Patients in the cross group were evaluated three times: at baseline, after a 2-month control period of no treatment, and after subsequent 2-months of 40 HBOT sessions. HBOT protocol: Two months of 40 sessions (5 days/week), 90 minutes each, 100% oxygen at 2 ATA. We found that the neurological functions and life quality of all patients in both groups were significantly improved following the HBOT sessions while no improvement was found during the control period of the patients in the cross group. Results of SPECT imaging were well correlated with clinical improvement. Elevated brain activity was detected mostly in regions of live cells (as confirmed by CT) with low activity (based on SPECT) - regions of noticeable discrepancy between anatomy and physiology. CONCLUSIONS: The results indicate that HBOT can lead to significant neurological improvements in post stroke patients even at chronic late stages. The observed clinical improvements imply that neuroplasticity can still be activated long after damage onset in regions where there is a brain SPECT/CT (anatomy/physiology) mismatch.

99m Tc-albumin nanocolloid joint scintigraphy in rheumatoid arthritis patients who are in clinical remission - is remission real ?

OBJECTIVES: To make a comparison between the clinical data and the imaging results with 99mTc-nanocolloid scintigraphy in rheumatoid arthritis (RA) patients considered to be in remission. METHODS: Forty RA patients found to be in clinical remission according to the ACR and the EULAR (DAS28<2.6) criteria were studied. The group included 29 females and 11 males with a mean age of 60.8+/-13.5 years (range 22-86) and a mean disease duration of 13.4+/-7.7 years (range 2-23). The mean time of remission in the study group was 22.2+/-5.2 months (range 11-36). Each patient was given an intravenous injection of 555MBq of 99mTc-nanocalloid (NC). Spot views of the skeleton were taken and a SPECT-CT was done on the wrists and hands. A scan was considered positive when at least one of the hand joints showed increased tracer uptake. RESULTS: The 99mTc-nanocalloid scintigraphy was negative in 14 (35%) and positive for active joint disease in 26 (65%) patients. Twenty four out of the 26 patients with positive scan (92%) were sero-positive while those who had a negative scintigraphy were all sero-negative except one. No correlation was found between the type of treatment used, the time that elapsed from remission, or laboratory parameters (ESR CRP) and the scintigraphic results. CONCLUSIONS: The clinical criteria used for remission in RA are not consistent with the actual inflammatory activity in the joints. These results are especially emphasised in the subgroup of sero-positive patients.

FDG-PET imaging in Merkel cell carcinoma - value of head-to-toe scan.

A 63-year-old man was diagnosed with metastatic MCC. Preliminary staging PET scan with 18F-FDG was not done at the time of diagnosis. After completion of chemo- and radiotherapy, the patient underwent a CT scan of the area from the maxilla to the ischium; no evidence of disease was noted. Clinically, the patient was considered to be in remission. The CT scan was followed by head-to-toe FDG-PET scanning which revealed foci of metastatic disease in the right mid- thigh and left proximal calf. This case demonstrates the added value of head-to-toe FDG-PET for the detection of distant metastases in MCC.

[Comparison between D-dimer levels and lung scan in patients with suspected pulmonary embolism].

Pulmonary embolism (PE) is a critical situation that requires prompt diagnosis and treatment. Lately, the use of D-Dimer (DD) blood level test was recommended when PE is suspected. The goal of this work was to evaluate the association between DD levels and the results of lung scan in patients with suspected PE. 84 patients who were admitted due to suspected PE and met the inclusion criteria of having both DD test and lung scan within less than 7 days apart, were included in our study (age = 76 +/- 14, females = 58, males = 26). Comparison of lung scan results, DD level and diagnosis of PE at discharge was carried out. The subjects were classified into 2 groups according to the DD levels: group A = DD > or = 250 ng/mL--abnormal test, group B = DD < 250 ng/mL--normal test. Group A includes 67 patients, of which 29 (43%) were diagnosed as PE. In these subgroup lung scan showed high Probability (HP) for PE in 19 (66%), medium probability (MP) in 9 (31%) and low probability (LP) in 1 (3%). From the 38 (57%) patients who were not diagnosed with PE (non-PE), 5 (13%) had HP lung scan, 4 (11%) MP and 29 (76%) LP. Group B includes 17 patients, in which only one (6%) had diagnosed with PE and the rest (n = 16, 94%) had no PE. Of the latter subgroup 15 (94%) had LP lung scan and one MP scan. The one patient who was diagnosed with PE had a HP lung scan that was also confirmed with CT-angiography. DD and lung scan had similar sensitivity (96.7%) and high negative predictive value (NPV = 94.1% and 97.8% accordingly) for PE. On the other hand DD specificity is much lower (29.6%) in comparison to lung scan (81.5%). The results of this work support the use of DD test prior to lung scan, in order to rule out PE with relatively high probability.