Assessment of Inflammation in Pulmonary Artery Hypertension by 68Ga-Mannosylated Human Serum Albumin.

Rationale: Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.Objectives: We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent, 68Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA), that targets the mannose receptor (MR).Methods: We induced PAH in rats by monocrotaline injection. Tissue analysis, echocardiography, and 68Ga-NOTA-MSA PET were performed weekly in rats after monocrotaline injection and in those treated with either sildenafil or macitentan. The translational potential of 68Ga-NOTA-MSA PET was explored in patients with PAH.Measurements and Main Results: Gene sets related to macrophages were significantly enriched on whole transcriptome sequencing of the lung tissue in PAH rats. Serial PET images of PAH rats demonstrated increasing uptake of 68Ga-NOTA-MSA in the lung by time that corresponded with the MR-positive macrophage recruitment observed in immunohistochemistry. In sildenafil- or macitentan-treated PAH rats, the infiltration of MR-positive macrophages by histology and the uptake of 68Ga-NOTA-MSA on PET was significantly lower than that of the PAH-only group. The pulmonary uptake of 68Ga-NOTA-MSA was significantly higher in patients with PAH than normal subjects (P = 0.009) or than those with pulmonary hypertension by left heart disease (P = 0.019) (n = 5 per group).Conclusions:68Ga-NOTA-MSA PET can help diagnose PAH and monitor the inflammatory status by imaging the degree of macrophage infiltration into the lung. These observations suggest that 68Ga-NOTA-MSA PET has the potential to be used as a novel noninvasive diagnostic and monitoring tool of PAH.

Whole-Body Voxel-Based Personalized Dosimetry: The Multiple Voxel S-Value Approach for Heterogeneous Media with Nonuniform Activity Distributions.

Personalized dosimetry with high accuracy is becoming more important because of the growing interest in personalized medicine and targeted radionuclide therapy. Voxel-based dosimetry using dose point kernel or voxel S-value (VSV) convolution is available. However, these approaches do not consider the heterogeneity of the medium. Here, we propose a new method for whole-body voxel-based personalized dosimetry in heterogeneous media with nonuniform activity distributions-a method we refer to as the multiple VSV approach. Instead of using only a single VSV, as found in water, the method uses multiple numbers (N) of VSVs to cover media of various density ranges, as found in the whole body. Methods: The VSVs were precalculated using GATE Monte Carlo simulation and were convoluted with the time-integrated activity to generate density-specific dose maps. CT-based segmentation was performed to generate a binary mask image for each density region. The final dose map was acquired by the summation of N segmented density-specific dose maps. We tested several sets of VSVs with different densities: N = 1 (single water VSV), 4, 6, 8, 10, and 20. To validate the proposed method, phantom and patient studies were conducted and compared with the direct Monte Carlo approach, which was considered the ground truth. Finally, dosimetry on 10 patients was performed using the multiple VSV approach and compared with the single VSV and organ-based approaches. Errors at the voxel and organ levels were reported for 8 organs. Results: In the phantom and patient studies, the multiple VSV approach showed significant decreases in voxel-level errors, especially for the lung and bone regions. As the number of VSVs increased, voxel-level errors decreased, although some overestimations were observed at the lung boundaries. For the multiple VSVs (N = 8), we achieved a voxel-level error of 2.06%. In the dosimetry study, our proposed method showed greatly improved results compared with single VSV and organ-based dosimetry. Errors at the organ level were -6.71%, 2.17%, and 227.46% for single VSV, multiple VSV, and organ-based dosimetry, respectively. Conclusion: The multiple VSV approach for heterogeneous media with nonuniform activity distributions offers fast personalized dosimetry at the whole-body level, yielding results comparable to those of the direct Monte Carlo approach.

Assessment of regional GABA(A) receptor binding using 18F-fluoroflumazenil positron emission tomography in spastic type cerebral palsy.

Periventricular leukomalacia (PVL) due to hypoxic-ischemic insult to the immature brain, chorioamnionitis and maternal infection are the major etiological factors of spastic type cerebral palsy (CP). Despite advances in preventing and treating certain causes of CP, the number of patients has remained essentially unchanged and the pathophysiological mechanisms related to motor dysfunction remain poorly understood. In this study, statistical parametric mapping (SPM) analysis of cerebral gamma-aminobutyric acid (GABA) receptor PET imaging using [18F]-fluoroflumazenil showed increased GABA(A) receptor binding in the bilateral motor and visual cortices in spastic diplegia (SD) type CP patients (n = 20) compared with normal controls (n = 10). As GABA(A) receptor signaling modulates biological perception and production of movement, complex motor skills and use-dependent plasticity in the motor cortex, increased GABA(A) receptor binding in the motor cortex might play a important role in poor motor control. Decreased GABA(A) receptor binding was seen in the brain stem in SD CP patients, which appears to be related to spastic symptom.

Preparation of (188) Re-labeled paper for treating skin cancer.

For homogeneous delivery of beta radiation to skin cancer, we developed a simple method for preparing (188) Re-labeled nitrocellulose paper. The homogeneity and stability of the labeled paper were investigated. Absorbed dose estimates were calculated using the Monte-Carlo method. A 74-MBq (188) Re-labeled paper with 1-cm diameter delivered 147.2 Gy up to 1-mm depth after 2-h irradiation. Animal experiments on tumor-bearing mice showed that 50 Gy is an adequate dose for treating skin cancer. Tumors disappeared 7 days after irradiation in all the groups irradiated by 50 or 100 Gy. The (188) Re-labeled paper provided a convenient, economical, effective, and non-invasive method of treating skin cancer.

Diagnostic Accuracy of F-18 FDG-PET in the Assessment of Posttherapeutic Recurrence of Head and Neck Cancer.

The purpose of this study was to compare whole-body fluorine-18-fluorodeoxyglucose positron emission tomography (F-18 FDG-PET) with conventional imaging modalities (CI: CT/MRI) in the detection of recurrent head and neck cancer. Whole-body F-18 FDG-PET was performed in 45 patients (recurrence = 39; no recurrence = 16) with previous head and neck cancer. We compared detectability by the period from initial cancer treatment and treatment modalities. Thirty were PET-positive and 15 were PET-negative. The sensitivity, specificity, and accuracy of PET were 97%, 88%, and 93%, respectively (corresponding figures of CI were 73%, 85%, and 77%). In 18 patients who underwent PET less than 3 months after the completion of cancer treatment, the sensitivity, specificity, and accuracy were 100%, 86%, and 94%, while for CI, the corresponding figures were 67%, 71%, and 69%. In 18 patients who had undergone surgery, PET results were 14 true positive and 4 were true negative; significantly higher detectability than CI. Among the patients who were evaluated for more than 6 months or treated by radiotherapy without surgery, diagnostic accuracy was almost the same. Whole body F-18 FDG-PET was a valuable tool in the evaluation of post-therapeutic recurrence of head and neck cancer.