Injection Of 185MBq Research Articles

The first-in-human preclinical evaluation of the new probe [123I]I-PSMA-7 for real-time intraoperative targeted biopsy and SPECT/CT imaging in prostate cancer

PurposePSMA/PET has been increasingly used to detect PCa, and PSMA/PET-guided biopsy has shown promising results. However, it cannot be confirmed immediately whether the tissues are the targeted area. In this study, we aimed to develop a novel probe, [123I]I-PSMA-7. First, we hope that [123I]I-PSMA-7 can provide instant confirmation for prostate biopsy. Second, we hope it will help detect PCa.MethodsWe synthesized a high-affinity probe, [123I]I-PSMA-7, and evaluated its properties. We included ten patients with suspected PCa and divided them into two groups. The injection and biopsy were approximately 24 h apart. The activity in biopsy lesions was measured as the cpm by a γ-counter. Moreover, we enrolled 3 patients to evaluate the potential of [123I]I-PSMA-7 for detecting PCa.ResultsAnimal experiments verified the safety, targeting and effectiveness of [123I]I-PSMA-7, and the tumor-to-muscle ratio was greatest at 24 h, which confirmed the results of this study in humans. After injection of 185MBq [123I]I-PSMA-7, 18/55 cores were positive, and the cpm was significantly greater (4345 ± 3547 vs. 714 ± 547, P < 0.001), with an AUC of 0.97 and a cutoff of 1312 (sens/spec of 94.40%/91.90%). At a lower dose, 10/55 biopsy cores were cancerous, and the cpm was 2446 ± 1622 vs. 153 ± 112 (P < 0.001). The AUC was 1, with a cutoff value of 490 (sens/spec of 100%). When the radiopharmaceuticals were added to 370 MBq, we achieved better SPECT/CT imaging.ConclusionWith the aid of [123I]I-PSMA-7 and via cpm-based biopsy, we can reduce the number of biopsies to a minimum operation. [123I]I-PSMA-7 PSMA SPECT/CT can also provide good imaging results.Trial registrationChinese Clinical trial registry ChiCTR2300069745, Registered 24 March 2023

Cerebral glucose metabolism differs according to future weight change.

The brain is known to play a central role in controlling the desire to eat. We aimed to evaluate the brain regions that might have a long-term effect on eating behavior and weight changes. We utilized the data of cognitively normal subjects who are examined by several neurologic tests, and followed-up for 36months from Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and investigated to search the brain regions that are associated with future weight change. The weight of each subject was measured on each visit at baseline (W0), 36 (W36) months after brain 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET). Percentage (%) change of weight was calculated as follows: [(W36-W0)/W0]*100. We classified each subject's change into one of three categories: weight loss, stable, and weight gain. Dynamic 3-dimensional scans of six 5-min frames were acquired 30 mins after injection of 185MBq of FDG. Image analysis was done using Statistical Parametric Mapping 12. Ninety-six subjects were included in this study (male 54, female 42). Subjects with future weight gain showed hypometabolism in left cerebellum compared with those with future weight loss & stable. Percentage change of weight was positively associated with brain metabolism in right insula, and right caudate nucleus. In conclusion, subjects with future weight gain showed hypometabolism in left cerebellum, and percentage change of weight was positively associated with brain metabolism in right insula, and right caudate nucleus. This study raises the possibility that the brain glucose metabolism precedes the future weight change.

Primary radiation dosimetry of a novel PET radiopharmaceutical 68Ga-NODAGA-glycine in comparison with 99mTc-DTPA in renal studies.

In this study, we tried to estimate human absorbed dose of 68Ga-NODAGA-glycine as a new potential positron emission tomography (PET) renal agent based on the biodistribution data reported in healthy rats, and compare our estimation with the available absorbed dose data from technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA). The medical internal radiation dose (MIRD) formulation was applied to extrapolate from rats to human and to project the absorbed radiation dose for various organs in humans. S factor calculated by Monte-Carlo N-particle (MCNP) simulation and also this factor has been taken from the tables presented in MIRD pamphlet No.11. Hence, two radiation absorbed dose were calculated for organs. Our dose prediction shows that an 185MBq injection of gallium-68-1,4,7-triazacyclononane-1-γ-glutamylglycine-4,7-diacetic acid (68Ga-NODAGA-glycine) in humans might result in an estimated absorbed dose of 0.063mGy in the whole body when S factor calculated by MCNP simulation. The highest absorbed doses are observed in kidneys, lungs, spleen, liver, and red marrow with 3.510, 0.453, 0.335, 0.268, and 0.239mGy, respectively. In addition to, the estimated absorbed dose for total body after injection of 185MBq of 68Ga-NODAGA-glycine is 0.053mGy when S factor has been taken from MIRD pamphlet No.11. The highest absorbed doses are observed in kidneys, lungs, liver, spleen, and red marrow with 3.110, 0.438, 0.209, 0.203, and 0.203mGy, respectively. Comparison between human absorbed dose estimation for 68Ga-NODAGA-glycine and 99mTc-DTPA indicated that the absorbed dose of the most organs after injection of 99mTc-DTPA is higher than the amount after 68Ga-NODAGA-glycine. The results showed that 68Ga-NODAGA-glycine delivers lower dose to the patients. Also due to its application in PET (which offers higher sensitivity and spatial resolution compared to planar or SPET), 68Ga-NODAGA-glycine would be a superior choice than 99mTc-DTPA for renography and impose less radiation doses to patients.

124I]FIAU: Human dosimetry and infection imaging in patients with suspected prosthetic joint infection

IntroductionFialuridine (FIAU) is a nucleoside analog that is a substrate for bacterial thymidine kinase (TK). Once phosphorylated by TK, [124I]FIAU becomes trapped within bacteria and can be detected with positron emission tomography/computed tomography (PET/CT). [124I]FIAU PET/CT has been shown to detect bacteria in patients with musculoskeletal bacterial infections. Accurate diagnosis of prosthetic joint infections (PJIs) has proven challenging because of the lack of a well-validated reference. In the current study, we assessed biodistribution and dosimetry of [124I]FIAU, and investigated whether [124I]FIAU PET/CT can diagnose PJIs with acceptable accuracy. MethodsTo assess biodistribution and dosimetry, six subjects with suspected hip or knee PJI and six healthy subjects underwent serial PET/CT after being dosed with 74MBq (2mCi) [124I]FIAU intravenously (IV). Estimated radiation doses were calculated with the OLINDA/EXM software. To determine accuracy of [124I]FIAU, 22 subjects with suspected hip or knee PJI were scanned at 2–6 and 24–30h post IV injection of 185MBq (5mCi) [124I]FIAU. Images were interpreted by a single reader blinded to clinical information. Representative cases were reviewed by 3 additional readers. The utility of [124I]FIAU to detect PJIs was assessed based on the correlation of the patient's infection status with imaging results as determined by an independent adjudication board (IAB). ResultsThe kidney, liver, spleen, and urinary bladder received the highest radiation doses of [124I]FIAU. The effective dose was 0.16 to 0.20mSv/MBq and doses to most organs ranged from 0.11 to 0.76mGy/MBq. PET image quality obtained from PJI patients was confounded by metal artifacts from the prostheses and pronounced FIAU uptake in muscle. Consequently, a correlation with infection status and imaging results could not be established. Conclusions[124I]FIAU was well-tolerated in healthy volunteers and subjects with suspected PJI, and had acceptable dosimetry. However, the utility of [124I]FIAU for the clinical detection of PJIs is limited by poor image quality and low specificity.

Increased Brainstem Serotonergic Transporter Availability in Adult Migraineurs: an [(18)F]FP-CIT PET Imaging Pilot Study.

Recent studies have proposed central serotonergic dysfunction as a major pathophysiology of migraine. We investigated serotonin transporter (SERT) availability in migraineurs using F-18-N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([(18)F]FP-CIT) positron emission tomography (PET). Brain [(18)F]FP-CIT PET images were obtained in eight women with migraine during headache free phase and 12 healthy adult women, 120min after injection of 185MBq. Non-displaceable binding potential (BP ND) of [(18)F]FP-CIT, which is an estimate of SERT availability, was calculated at the brainstem and compared with clinical parameters. BP ND at the brainstem was significantly higher in adult migraineurs (n = 6, 1.15 ± 0.17) than healthy subjects (0.95 ± 0.14) (p = 0.04). Healthy subjects demonstrated negative correlation between brainstem BP ND and age (r = -0.64, p = 0.02), whereas this age-related decline pattern was not found in the migraineurs. Severity of migraine attack was significantly correlated with brainstem BP ND (r = 0.66, p = 0.02), when age and duration of illness were corrected. Increased SERT availability in the brainstem of adult migraineurs indicates low serotonin neurotransmission during headache-free phase. Patients who experience more painful headaches have lower serotonin neurotransmission. [(18)F]FP-CIT PET is a useful in vivo imaging technique for evaluating brainstem SERT availability in migraineurs.

An exploratory efficacy study of the amyloid imaging agent [(18)F]flutemetamol in Japanese Subjects.

The aim of the study presented was to investigate the brain uptake properties of the amyloid PET agent [(18)F]flutemetamol in Japanese healthy controls and clinically probable Alzheimer's disease (AD) patients, and to make a comparison with the results of a previously performed study on Caucasian subjects. [(18)F]flutemetamol was recently approved by the American Food and Drug Administration and the European Medicines Agency for visualization of amyloid in vivo. Since the first clinical study of [(18)F]flutemetamol-an (18)F derivative of the PET tracer 11C-Pittsburgh Compound B targeting β-amyloid--took place, several clinical studies have been performed, but few focusing on a Japanese population. In the Step A, three elderly healthy volunteers and three AD subjects underwent dynamic PET scanning 0-30 and 60-150min after injection of 185MBq [(18)F]flutemetamol. The brain volume of distribution (VT) was quantified using Logan's linear graphical analysis and as standardized uptake value ratios (SUVR) with a cerebellar reference. The optimal acquisition window was determined from brain time activity curves for Step B. In the Step B, 5 AD and 5 elderly healthy volunteers were scanned from 80 to 140min after intravenous injection of [(18)F]flutemetamol. The data from the two parts were pooled for estimation of overall efficacy. [(18)F]Flutemetamol injection was shown to be safe-no serious adverse events were reported during this study. A simplified SUVR estimate of the uptake of [(18)F]flutemetamol using a time window of 85-115min post injection successfully discriminated AD cases from healthy volunteers. AD subjects showed an elevated tracer uptake in prefrontal cortex, the lateral temporal cortex and precuneus amongst other regions. No significant [(18)F]flutemetamol PET differences could be seen between the Japanese AD cases in this study and those from an earlier Caucasian study, or between control subjects in Japanese and Caucasian studies. This study supports the use of [(18)F]flutemetamol PET in Japanese population as a marker of the presence of fibrillar β-amyloid. The lack of differences between the Japanese cohort and those from a previous Caucasian cohort supports the extrapolation of results from other Caucasian [(18)F]flutemetamol PET studies to the Japanese population.

Steal phenomenon-induced lung perfusion defects in pulmonary arteriovenous fistulas: assessment with automated perfusion SPECT-CT fusion images

Lung perfusion impairment in patients with pulmonary arteriovenous fistula (AVF) was evaluated by automated deep inspiratory breath-hold (DIBrH) perfusion single-photon emission computed tomography (SPECT)-CT fusion images. Participants were 14 patients with a single (N=6) or multiple nodular AVFs (N=8) diagnosed by contrast-enhanced CT scan and/or pulmonary angiography. After the injection of 185MBq Tc-99m-macroaggregated albumin, a whole-body scan was obtained to quantify an intrapulmonary right-to-left shunt. Subsequently, DIBrH SPECT was obtained using the continuous rotating acquisition mode of a dual-headed SPECT system, which was automatically coregistered with DIBrH CT. The anatomic relationship between AVF and perfusion defects was assessed on the fusion images. The whole-body scan depicted systemic organs indicating the presence of an intrapulmonary right-to-left shunt in all the patients. DIBrH SPECT showed 34 perfusion defects in these patients, which were located at the AVF and in the surrounding lungs of the AVF on the fusion images, regardless of the absence of morphologic abnormality on CT in all the patients. These defects were considered to be caused by the 'steal phenomenon' associated with the high and fast pulmonary arterial flow to each AVF, which were more extensive and severe in the multiple AVFs compared with a single AVF (P=0.0012), occasionally extending to the entire lobe with AVF or even to the adjacent lobe. In five patients, the fusion images detected a total of six tiny AVFs with unexpectedly extensive 'steal phenomenon'-induced defects, which had been missed by other radiological imaging techniques. The summed value of the shunt index estimated by the whole-body scan and the lung perfusion defect extent estimated by DIBrH SPECT was significantly correlated with PaO2 in all the patients (P < 0.0001), with a better correlation compared with the shunt index alone. In addition to the right-to-left shunt, 'steal phenomenon'-induced perfusion defects are common in the surrounding lung of pulmonary nodular AVF and cause hypoxemia. DIBrH SPECT-CT fusion images contribute to the objective evaluation of 'steal phenomenon'-induced lung perfusion impairment in AVF and the detection of tiny, subtle AVFs that may be missed by other radiological imaging techniques.