Can99mTc-MDP-SPECT/CT Differentiate Loosening and Infection After Hip and Knee Replacements?

Background: Prosthetic loosening and infection are still common complications after joint replacement. Over the past few years, single-photon emission computed tomography-computed tomography (SPECT/CT) was widely used and showed unique value based on the combination of anatomic and metabolic information of foci. However, its performance in differentiating between prosthetic loosening and periprosthetic infection after joint replacement is still the focus of clinicians and deserves further investigation. Purpose: This retrospective study was aimed to determine whether bone scintigraphy combined with SPECT/CT still can differentiate prosthetic infection from loosening in patients after joint replacement. The differential efficacy in hip and knee prosthesis was also analyzed. Blood biomarkers for the diagnosis of periprosthetic infection were also evaluated. Patients and methods: Data sets of 74 prosthetic joints (including knees and hips), with suspected prosthetic loosening or infection between 2015 and 2021, were evaluated. Besides the results of nuclear imaging, X-ray images and serum biomarker were also recorded. Telephone follow-up and revision surgery after SPECT/CT were used as a gold standard. The sensitivity and accuracy of different imaging modalities were calculated by Chi-square test. The diagnostic efficacy of imaging methods and serum biomarkers were then analyzed by the area under curve (receiver operating characteristic curves, ROC) in SPSS 26. Results: In all, 47 joints (14 knees and 33 hips) were confirmed as aseptic loosening, while 25 joints (18 knees and 7 hips) were confirmed as infection. The sensitivity and accuracy of SPECT combined with SPECT/CT imaging were the highest (92.86% and 87.84%, respectively). The differential efficacy of bone scintigraphy combined with SPECT/CT imaging was also better than any other single imaging modality. In the analysis of involved prosthesis, prosthetic loosening occurred more in hip prosthesis and knee prosthesis was easily infected (P < 0.05). Finally, the sensitivity of ESR and CRP were 80% and 84%, respectively. Conclusions: Bone scintigraphy with hybrid SPECT/CT remains encouraging in differentiating prosthetic infection from loosening after joint replacement. The diagnostic efficacy of differentiation in hip prosthesis was better than knee. Serum biomarkers cannot be used alone to differentiate prosthetic infection from loosening.

Radiosynthesis and in-vitro identification of a molecular probe 131I-FAPI targeting cancer-associated fibroblasts.

Purpose: Fibroblast activation protein (FAP) is highly expressed in the mesenchyme of most malignant epithelial tumors, while its expression is low in normal tissues. FAP inhibitors (FAPIs) bind specifically to FAP and are used for tumor-targeted diagnosis and therapy. The aim of this study was to radiosynthesize a novel molecular probe 131I-FAPI and evaluate its in-vitro targeting and biological characteristics. Methods: The structurally modified FAPI was labelled with 131I through the chloramine-T method. The radiolabeling rate was then detected by thin-layer chromatography (TLC). The stability of 131I-FAPI was determined at PBS (room temperature) and serum (37°C). Its hydrophilicity was calculated by measuring its lipid-water partition coefficient. Pancreatic cancer PANC-1 cell line and glioma U87 cell line were cultured in vitro. Cell uptake assay was used to show the binding ability of 131I-FAPI. The CCK-8 assay was used to calculate the inhibitory effects of 131I-FAPI at different time points (4h, 8h, 12h, 24h, 48h) after comparing with the 131I and FAPI. The before-and-after-24h scratch areas of the two cells were determined in order to verify the effect of 131I-FAPI on the migration ability of the cells. Results: The radiolabeling rate was (84.9 ± 1.02) %. The radiochemical purity of 131I-FAPI remained over 80% in both 25°C PBS and 37°C serum. The value of the lipid-water partition coefficient was -0.869 ± 0.025, indicating the hydrophilic of the probe. The cellular uptake assay showed that U87 cells had a specific binding capacity for 131I-FAPI. In cell inhibition assays, the inhibitory effect of 131I-FAPI on U87 cells increased with time. The results of cell scratch assay showed that 131I-FAPI had the strongest inhibitory effect on the migratory ability of U87 cells compared with 131I and FAPI (P<0.001). Conclusion: 131I-FAPI was synthesized with good in-vitro stability and hydrophilic properties. It can be specifically bound by U87 cells. The proliferation and migration of U87 cells can be effectively inhibited. 131I-FAPI is promising to become a therapeutic probe.

A novel molecular imaging probe [99mTc]Tc-HYNIC-FAPI targeting cancer-associated fibroblasts.

Fibroblast activation protein (FAP) is higher expressed on cancer-associated fibroblasts (CAFs) in most malignant epithelial neoplasms, which is lower expressed in normal tissues. As a promising small molecular probe, FAP inhibitor (FAPI) shows the specific binding to FAP. This study aimed to explore a novel molecular probe [99mTc]Tc-HYNIC-FAPI targeting CAFs. The in vitro characteristics of the probe were also evaluated. The FAPI targeting FAP was designed, synthesized and conjugated with the chelator 6-hydrazinylnicotinic acid (HYNIC) for radiolabeling with 99mTc. The radiolabeling yield, radiochemical purity and stability were evaluated by Instant thin-layer chromatography (ITLC) and High performance liquid chromatography (HPLC). Lipophilicity was performed by the distribution coefficient test. The binding and migration ability of the probe was assessed using the FAP transfected tumor cell line. The radiolabeling yield of [99mTc]Tc-HYNIC-FAPI was (97.29 ± 0.46) %. The radiochemical purity was more than 90% and kept stable until 6 h. The radioligand was shown as lower lipophilicity, of which logD7.4 value was - 2.38 [Formula: see text] 0.13. In vitro experiments, the results indicated that the probe showed binding properties, and inhibited the migration of tumor cells. The novel [99mTc]Tc-HYNIC-FAPI probe was successfully radiosynthesized and exhibited good radiochemical purity, stability and in vitro binding ability to tumor cells. The [99mTc]Tc-HYNIC-FAPI will be a promising SPECT/CT imaging probe.

Gender-Related Differences in Regional Cerebral Glucose Metabolism in Normal Aging Brain.

Objectives: This study was aimed to investigate the gender-related differences of regional cerebral glucose metabolism in healthy people along the age using 18F-FDG PET/CT. Methods: We recruited 344 healthy volunteers, including 217 males and 127 females (age range: 40-89 years old). All subjects underwent fluorine-18 fluorodeoxyglucose(18F-FDG) positron emission tomography (PET). All the data were divided into four groups for every 10 years old. Each participant was carefully screened from PET, MR, and other examinations in order to exclude the abnormalities, such as neurodegenerative or psychiatric disorders, alcohol/abuse, cerebral vascular disorders, metabolic diseases like diabetes mellitus and hyperthyroidism, and other systemic malignancies. The 40-50 years old group was set as the baseline group. Statistical parametric mapping (SPM) analysis was employed to illustrate the differences among groups. Results: Compared to the baseline group, whether in a cohort or different gender groups, the decrease of brain glucose metabolism was shown in the bilateral frontal lobe, anterior cingulate gyrus, and the bilateral temporal lobe. In males, the regions of decreased metabolism were bilateral frontal lobe, caudate nucleus, and cingulate gyrus, whereas that of females were left occipital lobe, cerebellum, and the thalamus. However, the overall decrease of brain metabolism in men and women began from the age of 60s, an aggravated decrease from 70s was only observed in males. Conclusion: (1) An obviously decreased brain metabolism was found from 60 years old, especially in the bilateral frontal lobe, bilateral temporal lobe, and inferior cingulate gyrus; (2) We found specific brain metabolic differences between genders, including the caudate nucleus region in males and the occipital lobe region in females; and (3) The aging trend is different between genders.

18F-FDG PET/CT in a Patient With Malignant Pheochromocytoma Recurrence and Bone Metastasis After Operation-Case Report and Review of the Literature.

Introduction: Bone metastasis of malignant pheochromocytoma is a rare disease. We report a patient with a 10-year history who underwent 18F-FDG PET/CT to detect bone metastasis and receive radiotherapy and chemotherapy with complete response for bilateral iliac pain. Case presentation: A 48-year-old male patient complained of dizziness, hypertension, and bilateral iliac pain for 2 months. The patient had a history of resection of bilateral malignant adrenal pheochromocytoma 10 years earlier, and all complaints were relieved immediately after operation. 18F-FDGPET/CT showed abdominal lymph node uptake and multiple bone uptake, as well as multiple brown fat uptake. A biopsy of the left ilium confirms the metastasis of malignant pheochromocytoma. Discussion: In our literature review, we discuss the metastasis of pheochromocytoma reported by some scholars, and the role of radionuclides such as 18F-FDG PET/CT, 18F-DOPA PET/CT, I-123MIBG, and 68Ga-DOTATATE PET, in the diagnosis of malignant pheochromocytoma. The patient above is a good case for clinicians in the diagnosis and treatment of metastatic pheochromocytoma, especially in some hospitals with only 18F-FDG imaging agents. Conclusion: A review of this case and similar rare cases in the literature illustrates the importance of 18F-FDG PET/CT in the diagnosis of malignant pheochromocytoma.