Expression of glutamate carboxypeptidase II in the glial tumor recurrence evaluated in vivo using radionuclide imaging

Glutamate carboxypeptidase II (GCP), also known as prostate specific membrane antigen (PSMA) has been found to be expressed in glioma vasculature in in-vitro studies. GCP expression can be traced with the use of [68Ga]Ga-PSMA-11 PET/CT used routinely for prostate cancer imaging. The aim of this paper was to analyze GCP expression in the recurrent glial tumors in vivo. 34 patients (pts.) aged 44.5 ± 10.3 years with suspicion of recurrence of histologically confirmed glioma grade III (6 pts.) and grade IV (28 pts.) were included in the study. All patients underwent contrast-enhanced MR and [68Ga]Ga-PSMA-11 PET/CT. No radiopharmaceutical-related adverse events were noted. PET/CT was positive in all the areas suspected for recurrence at MR in all the patients. The recurrence was confirmed by histopathological examinations or follow-up imaging in all cases. The images showed a very low background activity of the normal brain. Median maximal standard uptake value (SUVmax) of the tumors was 6.5 (range 0.9–15.6) and mean standard uptake value (SUVmean) was 3.5 (range 0.9–7.5). Target-to-background (TBR) ratios varied between 15 and 1400 with a median of 152. Target-to-liver background ratios (TLR) ranged from 0.2 to 2.6, the median TLR was 1.3. No significant difference of the measured parameters was found between the subgroups according to the glioma grade. High GCP expression in the recurrent glioma was demonstrated in-vivo with the use of [68Ga]Ga-PSMA-11 PET/CT. As the treatment options in recurrent glioma are limited, this observation may open new therapeutic perspectives with the use of radiolabeled agents targeting the GCP.

FAPI-04 Uptake in Healthy Tissues of Cancer Patients in 68Ga-FAPI-04 PET/CT Imaging

Objective. The aim of this study is to investigate the uptake of 68Ga-FAPI-04 in normal tissues and calculate standardized uptake values (SUVs) for various organs in the body. Methods. A total of 49 patients who underwent 68Ga-FAPI-04 PET/CT were included in our study. The following organs were identified on CT images: brain, parotid, and submandibular glands, palatine tonsils, thyroid, lymph nodes (if present), breasts, lungs, thymus, left ventricle walls, mediastinal blood pool, vertebral bone marrow, liver, spleen, pancreas, stomach, small and large intestines, adrenal glands, kidneys, uterus, testes, and prostate. Median, minimum, and maximum values (max) and average (avg) values of standard uptake value (SUV) of tissues and organs were calculated. Results. The accumulation of 68Ga-FAPI in normal organs showed variations. The cerebral/cerebellar cortex exhibited no 68Ga-FAPI uptake, while the scalp showed low uptake. Low uptake was also observed in the lung parenchyma, esophagus, left ventricle walls, nipple, and glandular breast tissue. In the abdominopelvic area, the pancreas exhibited low uptake, which was higher in the tail region. Low uptake was observed in the renal cortex. Intense 68Ga-FAPI uptake was observed throughout the uterus, which was higher in the corpus. There was no uptake of 68Ga-FAPI in the bone cortex and medulla. Conclusion. We determined the physiological uptake and SUVmax of FAPI-04 in different tissues and organs and created a guide for researchers.

Impact of time of flight and point spread function on quantitative parameters of lung lesions in 18F-FDG PET/CT

Background Image reconstruction algorithm is one of the important factors affecting the quantitative parameters of PET/CT. The purpose of this study was to investigate the effects of time of flight (TOF) and point spread function (PSF) on quantitative parameters of lung lesions in 18F-FDG PET/CT. Methods This retrospective study evaluated 60 lung lesions in 39 patients who had undergone 18F-fluoro-deoxy-glucose (FDG) PET/CT. All lesions larger than 10 mm in diameter were included in the study. The PET data were reconstructed with a baseline ordered-subsets expectation–maximization (OSEM) algorithm, OSEM + PSF, OSEM + TOF and OSEM + TOF + PSF respectively. The differences of maximum standard uptake value (SUVmax), mean standard uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG)and signal to noise ratio (SNR)were compared among different reconstruction algorithms. Results Compared with OSEM reconstruction, using OSEM + TOF + PSF increased SUVmean and SUVmax by 23.73% and 22.71% respectively, and SNR increased by 70.18%, MTV decreased by 23.84% (p < 0.01). The percentage difference was significantly higher in smaller lesions (diameter 10–22 mm) than in larger lesions (diameter 23–44 mm), and significantly higher in low contrast lesions (SNR ≤ 15.31) than in high contrast lesions (SNR > 15.31). The difference of TLG among various reconstruction algorithms is relatively small, the highest value is − 6.48% of OSEM + TOF + PSF, and the lowest value is 0.81% of OSEM + TOF. Conclusion TOF and PSF significantly affected the quantitative parameters of lung lesions in 18F-FDG PET/CT. OSEM + TOF + PSF can significantly increased SUVmax, SUVmean and SNR, and significantly reduce MTV, especially in small lesions and low contrast lesions. TLG can be relatively stable in different reconstruction algorithms.

68Ga-EMP-100 PET/CT—a novel ligand for visualizing c-MET expression in metastatic renal cell carcinoma—first in-human biodistribution and imaging results

Background 68Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC. Methods Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUVmean) and SUVmax measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually. Results Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUVmax of 4.35 and SUVmean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUVmax 9.05 (4.86–29.16)), followed by bone metastases (SUVmax 5.56 (0.97–15.85)), and lymph node metastases (SUVmax 3.90 (2.13–6.28)) and visceral metastases (SUVmax 3.82 (0.11–16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines. Conclusion Targeting c-MET expression, 68Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68Ga-EMP-100 as a biomarker in mRCC patients.

Clinical Implications of Amyloid-Beta Accumulation in Occipital Lobes in Alzheimer’s Continuum

A substantial amount of amyloid-beta (Aβ) accumulates in the occipital cortices; however, it draws less attention. We investigated the clinical implications of Aβ accumulation in the occipital lobes in the Alzheimer’s disease (AD) continuum. [18F]-Florbetaben amyloid PET scans were performed in a total of 121 AD or amnestic mild cognitive impairment (aMCI) patients. Of the 121 patients, 74 Aβ positive patients were divided into occipital Aβ positive (OCC+) and occipital Aβ negative (OCC−) groups based on Aβ accumulation in the bilateral occipital lobes. The OCC+ group (41/74, 55.4%) was younger and had a younger age at onset than the OCC− group. The OCC+ group also had an increased standard uptake value ratio in the occipital lobes and greater cortical thinning in relevant areas. The OCC+ group had a higher global deterioration scale, lower performance for the copy, immediate recall, delayed recall, and recognition in Rey–Osterrieth Complex Figure tests than the OCC- group, although both groups had similar disease durations. AD or aMCI patients in the OCC+ group exhibited features noted in early onset AD with relevant neuropsychological and image findings. Occipital Aβ positivity in amyloid PET scans need to be considered as an underestimated marker of early onset AD continuum.

Feasibility of a Drug-Releasing Radiofrequency Ablation System in a Porcine Liver Model

The objective of this study was to investigate the feasibility of a newly developed anticancer drug-releasing radiofrequency ablation (RFA) system in a porcine liver model. A 15-gauge drug-releasing cooled wet electrode (DRCWE) was newly developed to improve the RFA efficacy for creating a large ablation as well as for simultaneously delivering an anticancer drug to the tumor margin. Nine ablations in three pigs were performed by the DRCWE. The sectioned liver specimens were evaluated by measuring the ablation zone by a positron emission tomography/magnetic resonance imaging examination to investigate whether 18F-fluorodeoxyglucose was exactly diffused. Volumes of the ablation zones released drug injection volumes, circularity, retention rate defined as the ratio between an estimated and injection dose, and the standard uptake value were assessed. The drug-releasing RFA was technically successful without procedural-related complications. During the procedure, the color changes of the ablated zones of the liver were observed in all specimens. The mean drug injection volume was higher than the ablated volumes (17.21 ± 2.85 vs. 15.22 ± 2.30 cm3) and the circularity was 0.72 ± 0.08. Moreover, the retention rate was 72.89% ± 4.22% and the mean standard uptake value was 0.44 ± 0.05. The drug-releasing RFA system was feasible not only for local ablation but also for the delivery of anticancer drugs. The results of this study indicate that this novel strategy of localized RFA with a drug delivery system could be a promising option for the prevention of local recurrence rates.