IgG4-related disease (IgG4-RD) is an increasingly recognized clinicopathological disorder with immune-mediated inflammatory lesions mimicking malignancies. A cohort study was prospectively designed to investigate the value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in characterizing IgG4-RD.

Purpose: Despite the use of fluorescence-guided surgery (FGS), maximum safe resection of glioblastoma multiforme (GBM) remains a major challenge. It has restricted surgeons between preoperative diagnosis and intraoperative treatment. Currently, an integrated approach combining preoperative assessment with intraoperative guidance would be a significant step in this direction.

Idiopathic pulmonary fibrosis (IPF) is a lethal, chronic, progressive disease characterized by formation of scar tissue within the lungs. Because it is a disease of unknown etiology, it is difficult to diagnose, to predict disease course and to devise treatment strategies. Recent evidence suggests that activated macrophages play key roles in the pathology of IPF. Therefore, imaging probes that specifically recognize these pools of activated immune cells could provide valuable information about how these cells contribute to the pathobiology of the disease. Here we demonstrate that cysteine cathepsin-targeted imaging probes can be used to monitor the contribution of macrophages to fibrotic disease progression in the bleomycin-induced murine model of pulmonary fibrosis. Furthermore, we show that the probes highlight regions of macrophage involvement in fibrosis in human biopsy tissues from IPF patients. Finally, we present first-in-human results demonstrating non-invasive imaging of active cathepsins in fibrotic lesions of patients with IPF. Together, our findings validate small molecule cysteine cathepsin probes for clinical PET imaging and suggest that they have the potential to be used to generate mechanistically-informative molecular information regarding cellular drivers of IPF disease severity and progression.

Purpose: This study was to assess a gastrin-releasing peptide receptor (GRPR) and integrin αvβ3 dual targeting tracer ⁶⁸Ga-BBN-RGD for positron emission tomography (PET)/computed tomography (CT) imaging of breast cancer and metastasis. Materials and Methods: Twenty-two female patients were recruited either with suspected breast cancer on screening mammography (n = 16) or underwent breast cancer radical mastectomy (n = 6). All the 22 patients underwent PET/CT at 30-45 min after intravenous injection of ⁶⁸Ga-BBN-RGD. Eleven out of 22 patients also accepted ⁶⁸Ga-BBN PET/CT within 2 weeks for comparison. A final diagnosis was made based on the histopathologic examination of surgical excision or biopsy. Results: Both the primary cancer and metastases showed positive ⁶⁸Ga-BBN-RGD accumulation. The T/B ratios of ⁶⁸Ga-BBN-RGD accumulation were 2.10 to 9.44 in primary cancer and 1.10 to 3.71 in axillary lymph node metastasis, 3.80 to 10.7 in distant lymph nodes, 2.70 to 5.35 in lung metastasis and 3.17 to 22.8 in bone metastasis, respectively. For primary lesions, the SUVmax from ⁶⁸Ga-BBN-RGD PET in ER positive group was higher than that in ER negative group (P < 0.01). For both primary and metastatic lesions, SUVmean quantified from ⁶⁸Ga-BBN-RGD PET correlated well with both GRPR expression and integrin αvβ3 expression. Conclusion: This study demonstrated significant uptake of a new type of dual integrin αvβ3 and GRPR targeting radiotracer in both the primary lesion and the metastases of breast cancer. ⁶⁸Ga-BBN-RGD PET/CT may be of great value in discerning both primary breast cancers, axillary lymph node metastasis and distant metastases.

This study was designed to assess the diagnostic value of ⁶⁸Ga-NOTA-PRGD2 (NOTA-PRGD2 is NOTA-PEG4-E[c(RGDfK)]₂) PET/CT in lung cancer. Methods: Ninety-one patients (48 men and 43 women; age, 22–82 y) with suspected lung lesions on CT were enrolled with informed consent. Immediately after intravenous injection of 117.7 ± 37.7 MBq of ⁶⁸Ga-NOTA-PRGD2, 15 patients underwent dynamic whole-body PET/CT scans for 1–2 h, and the remaining 76 patients underwent whole-body PET/CT scans at 30 ± 10 min after bolus injection. Each patient also underwent standard ¹⁸F-FDG PET/CT for comparison. Results: No side effect was found after ⁶⁸Ga-NOTA-PRGD2 injection. ⁶⁸Ga-NOTA-PRGD2 was rapidly cleared from the blood pool and primarily excreted through the urinary system. The standardized uptake values of proven malignancies were significantly higher than those of the benign ones. With an average standardized uptake value of greater than 1.3 being considered malignant, the sensitivity, specificity, and accuracy of ⁶⁸Ga-NOTA-PRGD2 PET/CT in diagnosing lung cancer were 83.8% (57/68), 91.3% (21/23), and 85.7% (78/91), respectively. The diagnostic value of ⁶⁸Ga-NOTA-PRGD2 for lung cancer is comparable to that of ¹⁸F-FDG PET/CT. However, ⁶⁸Ga-NOTA-PRGD2 PET/CT is more specific than ¹⁸F-FDG PET/CT in assessing lymph node metastasis, with positive and negative predictive values of 90.0% (27/30) and 93.8% (121/129), respectively, whereas those of ¹⁸F-FDG PET/CT were 30.2% (29/96) and 90.5% (57/63), respectively. Conclusion: This study indicates the efficacy of ⁶⁸Ga-NOTA-PRGD2 PET/CT in lung cancer diagnosis. ⁶⁸Ga-NOTA-PRGD2 PET/CT shows significant advantage over ¹⁸F-FDG PET/CT in judging metastatic lymph nodes with higher specificity.

Integrin α_vβ₃ is overexpressed in both neovasculature and glioma cells. We aimed to evaluate ⁶⁸gallium-BNOTA-PRGD2 (⁶⁸Ga-PRGD2) as a new reagent for noninvasive integrin α_vβ₃ imaging in glioma patients. With informed consent, 12 patients with suspicious brain glioma, as diagnosed by enhanced magnetic resonance imaging (MRI) scanning, were enrolled to undergo ⁶⁸Ga-PRGD2 PET/CT and ¹⁸F-FDG PET/CT scans before surgery. The preoperative images were compared and correlated with the pathologically determined WHO grade. Next, the expression of integrin α_vβ₃, CD34, and K_i-67 were determined by immunohistochemical staining of the resected brain tumor tissue. Our findings demonstrated that ⁶⁸Ga-PRGD2 specifically accumulated in the brain tumors that were rich of integrin α_vβ₃ and other neovasculature markers, but not in the brain parenchyma other than the choroid plexus. Therefore, ⁶⁸Ga-PRGD2 PET/CT was able to evaluate the glioma demarcation more specifically than ¹⁸F-FDG PET/CT. The maximum standardized uptake values (SUVmax) of ⁶⁸Ga-PRGD2, rather than those of ¹⁸F-FDG, were significantly correlated with the glioma grading. The maximum tumor-to-brain ratios (TBRmax) of both tracers were significantly correlated with glioma grading, whereas ⁶⁸Ga-PRGD2 seemed to be more superior to ¹⁸F-FDG in differentiating high-grade glioma (HGG) from low-grade glioma (LGG). Moreover, ⁶⁸Ga-PRGD2 PET/CT showed different accumulation patterns for HGG of WHO grades III and IV. This is the first noninvasive integrin imaging study, to the best of our knowledge, conducted in preoperative patients with different grades of glioma, and it preliminarily indicated the effectiveness of this novel method for evaluating glioma grading and demarcation.