Value of Semi-Quantitative Parameters of 68Ga-FAPI-04 PET/CT in Primary Malignant and Benign Diseases: A Comparison with 18F-FDG.

Objectives: We aimed to compare the value of the semiquantitative parameters of 68Ga-labeled FAP inhibitor (68Ga-FAPI)-04 positron emission tomography/computed tomography (PET/CT) and 18F-fluorodeoxyglucose (18F-FDG) in diagnosing primary malignant and benign diseases. Materials and Methods: 18F-FDG and 68Ga-FAPI-04 PET/CT images of 80 patients were compared. Semiquantitative parameters, including maximum standardized uptake value (SUVmax), mean SUV (SUVmean), peak SUV (SUVpeak), peak SUV by lean body mass (SULpeak), metabolic tumor volume (or tumor volume of FAPI; FAPI-TV), and TLG (or total lesion activity of FAPI; FAPI-TLA), were automatically obtained using the IntelliSpace Portal image processing workstation with a threshold of 40% SUVmax. The liver blood pool was measured as the background, and the tumor-to-background ratio (TBRliver) was calculated. Results: In all malignant lesions, FAPI-TV and FAPI-TLA were higher in 68Ga-FAPI-04 PET/CT than in 18F-FDG. In the subgroup analysis, 68Ga-FAPI-04 had higher FAPI-TV and FAPI-TLA and lower SUVmax than 18F-FDG had in group A, including gynecological tumor, esophageal, and colorectal cancers. However, six semiquantitative parameters were higher in group B (the other malignant tumors). For the benign diseases, SUVmax, SUVmean, SUVpeak, and SULpeak were lower in 68Ga-FAPI-04 PET/CT than in 18F-FDG. 68Ga-FAPI-04 PET/CT showed a lower liver background and a higher TBRliver than 18F-FDG did. 68Ga-FAPI-04 PET/CT had higher accuracy, sensitivity, and specificity than 18F-FDG had. Conclusion: More accurate semiquantitative parameters and lower abdominal background in 68Ga-FAPI-04 PET/CT make it more competitive in the differential diagnosis of malignant and benign diseases than in 18F-FDG.

OsTKPR1 proteins with a single amino acid substitution fail the synthesis of a specific sporopollenin precursor and cause abnormal exine and pollen development in rice.

Fatty acid derivatives are key components of rice pollen exine. The synthesis of aliphatic sporopollenin precursors are initiated in the plastids of the tapetal cells, followed by multiple-step reactions conducted in the endoplasmic reticulum (ER). However, the relative contribution of different precursors to the precise structure of sporopollenin remains largely elusive, let alone the underlying mechanism. Here, we report that two complete male sterile mutants ostkpr1-3 (Tetraketide α-pyrone reductase 1-3, with OsTKPR1P124S substitution) and ostkpr1-4 (with truncated OsTKPR1stop) are defective in pollen exine, Ubisch body and anther cuticle development where ostkpr1-4 display severer phenotypes. Remarkably, OsTKPR1 could produce reduced hydroxylated tetraketide α-pyrone and reduced tetraketide α-pyrone, whereas OsTKPR1P124S fails to produce the latter. Pairwise interaction assays show that mutated OsTKPR1P124S is able to integrate into a recently characterized metabolon, thus its altered catalytic activity is not due to dis-integrity of the metabolon. In short, we find that reduced tetraketide α-pyrone is a key sporopollenin precursor required for normal exine formation, and the conserved 124th proline of OsTKPR1 is essential for the reduction activity. Therefore, this study provided new insights into the sporopollenin precursor constitution critical for exine formation.

Therapeutic efficacy and imaging assessment of the HER2-targeting chemotherapy drug ZHER2:V2-pemetrexed in lung adenocarcinoma Xenografts.

Chemotherapy has always been the first therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) with untreatable oncogenic mutations. However, chemotherapy has demonstrated limited success and is associated with severe side effects. This research aimed to investigate the antitumor efficacy and cytotoxic safety of the conjugate ZHER2:V2-pemetrexed, a novel targeted chemotherapeutic drug. In this context, human epidermal growth factor receptor 2 (HER2) + A549 lung xenografts were treated using ZHER2:V2-pemetrexed, pemetrexed or physiological saline. Therapeutic efficacy was monitored by single photon emission computed tomography (SPECT) imaging using the 99mTc-labeled ZHER2:V2-pemetrexed conjugate and further confirmed by performing apoptosis assays using flow cytometry analysis and hematoxylin-eosin (H&E) staining. To evaluate the expression of HER2 in tumor tissues, immunohistochemistry was performed, accompanied by quantitative analysis using flow cytometry. A toxicological evaluation was also conducted. Imaging with 99mTc-ZHER2:V2-pemetrexed demonstrated that in HER2+ A549 models, ZHER2:V2-pemetrexed showed better antineoplastic effects than pemetrexed. Compared with pemetrexed, the results from the pathological and flow cytometry analyses also revealed that ZHER2:V2-pemetrexed exhibits high antitumor activity against A549 tumors, inducing necrosis, apoptosis and cell cycle arrest. In addition, the clinical signs of toxicity in the ZHER2:V2-pemetrexed treated group were reduced compared with those in the pemetrexed treated group. These data revealed that the ZHER2:V2-pemetrexed conjugate encompasses promising targeted antitumor activity against HER2-positive lung adenocarcinoma, with reduced side effects compared with pemetrexed. Thus, the ZHER2:V2-pemetrexed conjugate may serve as a novel molecular agent with tremendous clinical breakthrough potential in the diagnosis and treatment of HER2-positive lung adenocarcinoma.