Objective: Overexpression of human epidermal growth factor receptor-2 (HER2) in breast cancers provides promising opportunities for imaging and targeted therapy. Developing HER2 targeted positron emission tomography (PET) probes might be benefit for management of the disease. Small high-affinity scaffold proteins, affibodies, are ideal vectors for imaging HER2 overexpressed tumors. Despite of the initial success on development of 18F labeled ZHER2:342 affibody, the tedious synthesis producers, low yields and unfavorable pharmacokinetics may hinder the clinical use. 68Ga is an attractive positron emitter for PET imaging. A simple preparation of 68Ga labeled ZHER2:342 analog, 68Ga-NOTA-MAL-Cys-MZHER2:342, was reported in the study. The in vivo performances of the tracer for assessing HER2 status in breast cancers were also evaluated. Methods: NOTA-MAL conjugated Cys-MZHER2:342 was radiolabeled with 68Ga. The probe was evaluated by in vitro tests including stability and cell binding studies in breast cancer cells with different HER2 levels. In vivo evaluation was performed in mice bearing tumors using microPET imaging and biodistribution experiments. A PET/CT imaging study was initially performed in patients with breast cancers. Results: The tracer was synthesized in a straightforward chelation method with satisfactory non-decay corrected yield (81±5%) and radiochemical purity (>95%). In vivo micro-PET imaging showed that HER2 high levels expressed BT474 xenografts were more clear visualized than HER2 low levels expressed MCF-7 tumors (16.12 ± 2.69 ID%/g vs 1.32 ± 0.19 ID%/g at 1 h post-injection). The outcome was consistent with the immunohistochemical analysis. No significant radioactivity was accumulated in healthy tissues (less than 2% ID/g) except kidneys. In a preliminary clinical study, 68Ga-NOTA-MAL-Cys-MZHER2:342 PET imaging allowed more high-contrast detection of HER2 positive primary tumors (maximum standardized uptake value = 2.16±0.27) than those in HER2 negative primary focus (maximum standardized uptake value = 0.32±0.05). No detectable side-effects were found. Conclusion: In summary, this study indicates the significant efficiency of the 68Ga labeled HER2 affibody. Preclinical and clinical studies support the possibility of monitoring HER2 levels in breast cancers using 68Ga-NOTA-MAL-Cys-MZHER2:342. Advances in knowledge: The research investigated the feasibility of a 68Ga labeled HER2 affibody modified with a hydrophilic linker for breast cancer PET imaging. Favorable outcomes showed that the probe might be valuable for determining HER2 status of the disease.

Rationale: Although programmed death-ligand 1 (PD-L1) inhibitors have achieved efficacy in cancer therapy, their response rate is low. Differences in the prognosis of patients with cancer under anti-PD-L1 treatment are related to the PD-L1 level in tumors. Accurate PD-L1 detection can optimize the accuracy of tumor immunotherapy and avoid ineffective clinical diagnosis and treatments.

Background: Noninvasive myocardial imaging modalities, such as cardiac magnetic resonance (CMR), single photon emission computed tomography (SPECT), and Positron emission tomography (PET), are well-established and extensively used to detect cardiac amyloid (CA). The purpose of this study is to directly compare CMR, SPECT, and PET scans in the diagnosis of CA, and to provide evidence for further scientific research and clinical decision-making. Methods: PubMed, Embase, and Cochrane Library were searched. Studies used CMR, SPECT and/or PET for the diagnosis of CA were included. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR), diagnostic odds ratio (DOR), their respective 95% confidence intervals (CIs) and the area under the summary receiver operating characteristic (SROC) curve (AUC) were calculated. Quality assessment of included studies was conducted. Results: A total of 31 articles were identified for inclusion in this meta-analysis. The pooled sensitivities of CMR, SPECT and PET were 0.84, 0.98 and 0.78, respectively. Their respective overall specificities were 0.87, 0.92 and 0.95. Subgroup analysis demonstrated that ^99mTc-HMDP manifested the highest sensitivity (0.99). ^99mTc-PYP had the highest specificity (0.95). The AUC values of ^99mTc-DPD, ^99mTc-PYP, ^99mTc-HMDP were 0.89, 0.99, and 0.99, respectively. PET scan with ¹¹C-PIB demonstrated a pooled sensitivity of 0.91 and specificity of 0.97 with an AUC value of 0.98. Conclusion: Our meta-analysis reveals that SEPCT scans present better diagnostic performance for the identification of CA as compared with other two modalities.

This study aimed to investigate the diagnostic efficacy of [⁶⁸Ga]Ga-NYM046 PET/CT in animal models and patients with clear cell renal cell carcinoma (ccRCC) and to compare its performance with that of ¹⁸F-FDG PET/CT. Methods: The in vivo biodistribution of [⁶⁸Ga]Ga-NYM046 was evaluated in mice bearing OS-RC-2 xenografts. Twelve patients with ccRCC were included in the study; all completed paired [⁶⁸Ga]Ga-NYM046 PET/CT and ¹⁸F-FDG PET/CT. The diagnostic efficacies of these 2 PET tracers were compared. Moreover, the positive rate of carbonic anhydrase IX in the pathologic tissue sections was compared with the SUV_max obtained by PET/CT. Results: The tumor accumulation of [⁶⁸Ga]Ga-NYM046 at 1 h after injection in OS-RC-2 xenograft tumor models was 7.21 ± 2.39 injected dose per gram of tissue. Apart from tumors, the kidney and stomach showed high-uptake distributions. In total, 9 primary tumors, 96 involved lymph nodes, and 147 distant metastases in 12 patients were evaluated using [⁶⁸Ga]Ga-NYM046 and ¹⁸F-FDG PET/CT. Compared with ¹⁸F-FDG PET/CT, [⁶⁸Ga]Ga-NYM046 PET/CT detected more primary tumors (9 vs. 1), involved lymph nodes (95 vs. 92), and distant metastases (137 vs. 127). In quantitative analysis, the primary tumors’ SUV_max (median, 13.5 vs. 2.4; z = −2.668, P = 0.008) was significantly higher in [⁶⁸Ga]Ga-NYM046 PET/CT. Conversely, the involved lymph nodes’ SUV_max (median, 5.9 vs. 7.6; z = −3.236, P = 0.001) was higher in ¹⁸F-FDG PET/CT. No significant differences were found for distant metastases (median SUV_max, 5.0 vs. 5.0; z = −0.381, P = 0.703). Higher [⁶⁸Ga]Ga-NYM046 uptake in primary tumors corresponded to higher expression of carbonic anhydrase IX, with an R² value of 0.8274. Conclusion: [⁶⁸Ga]Ga-NYM046 PET/CT offers a viable strategy for detecting primary tumors, involved lymph nodes, and distant metastases in patients with ccRCC. Visual Abstract