Development of in-House Synthesis and Quality Control of [99mTc]Tc-PSMA-I&S.

Many radioactive PSMA inhibitory substances have already been developed for PET diagnostics and therapy of prostate cancer. Because PET radionuclides and instrumentation may not be available, technetium-99 m labelled tracers can be considered as a diagnostic alternative. A suitable tracer is [99mTc]Tc-PSMA-I&S, primarily developed for radio-guided surgery, which has been identified for diagnostics of prostate cancer. However, there is no commercial kit approved for the preparation of [99mTc]Tc-PSMA-I&S on the market. This work presents an automated process for the synthesis of [99mTc]Tc-PSMA-I&S concerning good manufacturing practice (GMP). We used a Scintomics GRP 4 V module, with the SCC software package for programming sequences for this development. The optimum reaction conditions were evaluated in preliminary experiments. The pH of the reaction solution was found to be crucial for the radiochemical yield and radiochemical purity. The validation of [99mTc]Tc-PSMA-I&S (n = 3) achieved a stable radiochemical yield of 58.7 ± 1.5% and stable radiochemical purities of 93.0 ± 0.3%. The amount of free [99mTc]TcO4− in the solution and reduced hydrolysed [99mTc]TcO2 was <2%. Our automated preparation of [99mTc]Tc-PSMA-I&S has shown reliability and applicability in the clinical setting.

Clinical value of semi-quantitative parameters in 68Ga-DOTANOC PET/CT in treatment and diagnostics of cranial meningioma in a single-center retrospective analysis.

BACKGROUND: The value of somatostatin-analogon PET tracers in theranostics in cranial meningioma has been demonstrated in several studies; however, the value of semi-quantitative parameters for therapy and patient outcome is still unclear. METHODS: A retrospective study was performed comparing measured semi-quantitative 68Ga-DOTANOC PET/CT parameters (maximum standardized uptake value = SUVmax, mean standardized uptake value = SUVmean, and metabolic tumor volume = MTV) and calculated ratios (SUVmax tumor to pituitary gland and SUVmax tumor to superior sinus sagittalis), versus the WHO grades and overall outcome. Patients with histological confirmed meningioma or high probability for meningioma in the previous cranial MRI were eligible. RESULTS: Thirty-two patients from January 2018 to February 2023 were retrospectively included. The WHO grade I meningioma was confirmed in 17 patients, the WHO grade II in five patients, and the WHO grade III in two patients, while in eight patients, diagnosis was solely based on MRI and 68Ga-DOTANOC PET/CT findings. In 12 cases, stable disease was present, in 15 cases, radiation therapy was chosen, in three cases, neurosurgery was preferred, while in two cases, palliative care was chosen. Median SUVmax values increased with the WHO grade (15.84, 17.22, and 28.4, p = 0.134, Kruskal-Wallis test), and no statistically significant difference was present for MTV, SUVmax, and calculated ratios. CONCLUSION: Increased SUVmax values in the tumor in 68Ga-DOTANOC PET/CT are associated with higher WHO grade, although further studies including larger patient collectives are needed to solidify this hypothesis.

Clinical value of semi-quantitative parameters in 68Ga-DOTANOC PET/CT in treatment and diagnostics of cranial meningioma in a single-center retrospective analysis.

BACKGROUND: The value of somatostatin-analogon PET tracers in theranostics in cranial meningioma has been demonstrated in several studies however, the value of semi-quantitative parameters for therapy and patient outcome is still unclear. METHODS: A retrospective study was performed comparing measured semi-quantitative 68Ga-DOTANOC PET/CT parameters (maximum standardized uptake value = SUVmax, mean standardized uptake value = SUVmean, and metabolic tumor volume = MTV) and calculated ratios (SUVmax tumor/to pituitary gland, SUVmax tumor to superior sinus sagittalis), versus WHO grades and overall outcome. Patients with histological confirmed meningioma or high probability for meningioma in previous cranial MRI were eligible. RESULTS: Thirty-two patients from January 2018 to February 2023 were retrospectively included. WHO grade I meningioma was confirmed in 17 patients, WHO grade II in five patients, WHO grade III in two patients, while in eight patients diagnosis was solely based on MRI and 68Ga-DOTANOC PET/CT findings. In 12 cases stable disease was present, in 15 cases radiation therapy was chosen, in three cases neurosurgery was preferred while in two cases palliative care was chosen. Median SUVmax values increased with WHO grade (15.84, 17.22, and 28.4, p = 0.134, Kruskal-Wallis-test) and no statistically significant difference was present for MTV, SUVmax, and calculated ratios, although the ratio for SUVmax tumor to superior sinus sagittalis had the lowest value of p = 0.067. CONCLUSION: Increased SUVmax values in the tumor in 68Ga-DOTANOC PET/CT are associated with higher WHO grade, although further studies including larger patient collectives are needed to solidify this hypothesis.

F18-FDG PET/CT in a patient with Antisynthetase Syndrome.

More prevalent in women than men, Antisynthetase Syndrome is a rare and poorly defined autoimmune disease associated with interstitial lung disease, polymyositis, and dermatomyositis. In addition to various diagnostic tools, imaging modalities are needed in certain situations. A 42-year-old woman with Anti-Jo-1-positive Antisynthetase Syndrome presented with thoracic muscular pain. She underwent whole-body Fluorodeoxyglucose positron emission tomography/computed tomography (F18-FDG PET/CT) to evaluate the total extent of the muscles affected. Depicting symptomatic symmetric myositis of the intercostal muscles, F18-FDG PET/CT additionally revealed unusually extensive fasciitis of the lower extremities.

18F-FDG PET/CT in Primary Mesothelioma of the Liver.

ABSTRACT: Primary malignant mesothelioma is a rarity among malignant liver tumors. We present the case of a 48-year-old woman presenting with increasing upper abdominal discomfort and inappetence accompanied by a weight loss of approximately 10 kg. CT and MRI revealed a highly suspicious mass lesion in the liver. 18F-FDG PET/CT performed for staging showed a pathological 18F-FDG uptake of the known liver tumor. Histology and immunohistochemistry indicated mesothelioma of the liver. Herein we present a rare case of primary mesothelioma in the liver with CT, MRI, and 18F-FDG PET/CT.

Diagnostic value of two-time point [68Ga]Ga-PSMA-11 PET/CT in the primary staging of untreated prostate cancer.

The emerging PET tracer [68Ga]Ga-PSMA-11 has been established for staging in prostate cancer (PCa). Aim was to determine the value of early static imaging in two-phase PET/CT. 100 men with newly diagnosed histopathologically confirmed untreated PCa who underwent [68Ga]Ga-PSMA-11 PET/CT from January 2017 to October 2019 were included. The two-phase imaging protocol consisted of an early static scan of the pelvis (6 min p.i.) and a late total-body scan (60 min p.i). Associations of semi-quantitative parameters derived via volumes of interest (VOI) with Gleason grade group and PSA were investigated. In 94/100 patients (94%) the primary tumor was detected in both phases. In 29/100 patients (29%) metastases were detected at a median PSA level of 32.2 ng/ml (0.41-503 ng/ml). In 71/100 patients (71%) without metastasis a median PSA level of 10.1 ng/ml (0.57-103 ng/ml) was observed (p = < 0.001). Primary tumors demonstrated a median standard uptake value maximum (SUVmax) of 8.2 (3.1-45.3) in early phase versus 12.2 (3.1-73.4) in late phase and a median standard uptake value mean (SUVmean) of 4.2 (1.6-24.1) in early phase versus 5.8 (1.6-39.9) in late phase, significantly increasing over time (p = < 0.001). Higher SUVmax and SUVmean were associated with higher Gleason grade group (p = 0.004 and p = 0.003, respectively) and higher PSA levels (p = < 0.001). In 13/100 patients the semi-quantitative parameters including SUVmax were declining in the late phase compared to early phase. Two-phase [68Ga]Ga-PSMA-11 PET/CT demonstrates a high detection rate for primary tumor of untreated PCa of 94% and improves diagnostic accuracy. Higher PSA levels and Gleason grade group are associated with higher semi-quantitative parameters in the primary tumor. Early imaging provides additional information in a small sub-group with declining semi-quantitative parameters in the late phase.

Atypical Presentation of Liver Metastases of Prostate Cancer in 68Ga-PSMA-11 PET/CT.

ABSTRACT: 68Ga-PSMA-11 (68Ga-prostate-specific membrane antigen-11) PET/CT continues to have a great clinical value for staging in prostate cancer. Lymph nodes and bone are the most typical metastatic sites of prostate cancer, whereas liver metastases are rare and usually show focally increased tracer uptake in 68Ga-PSMA-11 PET/CT. Here, we present an 88-year-old man with histologically proven metastatic castration-resistant prostate cancer and extensive PSMA-negative liver metastases identified by 68Ga-PSMA-11 PET/CT. This finding is remarkable because the decreased liver uptake of 68Ga-PSMA-11 may resemble a primary hepatic tumor.

Automated Synthesis of [68Ga]Ga-FAPI-46 on a Scintomics GRP Synthesizer.

[68Ga]Ga-FAPI-46 is a radiolabelled fibroblast activation protein inhibitor that selectively binds to fibroblast activation protein (FAP), which is overexpressed by cancer-associated fibroblasts (CAFs) in the tumour microenvironment. In recent years, radiolabelled FAP inhibitors (FAPIs) are becoming increasingly important in cancer diagnostics and also for targeted radionuclide therapy. Because of the increasing demand for radiolabelled FAPIs, automating the synthesis of these compounds is of great interest. In this work, we present a newly programmed automatic synthesis process of [68Ga]Ga-FAPI-46 on a Scintomics GRP module using two Galli Ad generators as a radionuclide source. Dedicated cassettes for the labelling of 68Ga-peptides were used without any modifications. The generators were connected via a three-way valve to the module and eluted automatically over a strong cation exchange (SCX) cartridge by using the vacuum pump of the synthesis module, eliminating the need to transfer the eluates into a separate vial. After a reaction step in HEPES buffer, the compound was purified by solid-phase extraction (SPE) over a Sep-Pak Light C18 cartridge. The evaluation of 10 routine syntheses of [68Ga]Ga-FAPI-46 resulted in a radiochemical yield of 72.6 ± 4.9%. The radiochemical purity was 97.6 ± 0.3%, and the amount of free gallium-68 and colloid was <2%. The final product fulfilled the quality criteria, which were adapted from relevant monographs of the European Pharmacopoeia (Ph. Eur.). This work presents the successful preparation of multiple doses of [68Ga]Ga-FAPI-46 in a GMP-compliant automated process for clinical use.

Radioiodination and Purification of [131I]ß-CIT and [131I]FP-CIT with an Automated Radiosynthesizer.

Dopaminergic transporter (DAT) imaging with single photon emission computed tomography (SPECT) is used to diagnose Parkinson's disease and to differentiate it from other neurodegenerative disorders without presynaptic dopaminergic dysfunction. The radioiodinated tropane alkaloids [123I]FP-CIT and [123I]ß-CIT enable the evaluation of the integrity of DATs. Commonly, the labeling of these compounds is performed by electrophilic substitution of the alkylstannylated precursors with radioactive iodine and following purification by HPLC or solid phase extraction (SPE). This work presents the first radioiodination of ß-CIT and FP-CIT with no carrier added [131I]NaI on a Scintomics GRP synthesis module. Free iodine-131 and impurities were removed by SPE over a C-18 Sep-Pak cartridge. We achieved a radiochemical yield of >75% and a radiochemical purity of >98% with both compounds. Our development of an automated synthesis on a commercially available synthesizer ensures robust and efficient labeling of [131I]FP-CIT and [131I]ß-CIT starting with low concentrated radioiodine.

Diagnostic value of F-18 FDG PET/CT in fever or inflammation of unknown origin in a large single-center retrospective study.

Cause determination is challenging in fever or inflammation of unknown origin (FUO/IUO) despite today's diagnostic modalities. We evaluated the value of F-18 FDG PET/CT in an unselected patient collective. This retrospective nonrandomized single-center study enrolled 300 male and female patients with FUO/IUO. PET/CT findings were compared with final clinical outcomes to determine the sensitivity, specificity, clinical significance, etiological distribution of final diagnoses, impact on treatment, role of white-blood cell count (WBC), and C-reactive protein (CRP). In 54.0% (162/300) PET/CT was the decisive exanimation for establishing the final diagnosis, in 13.3% (40/300) the findings were equivocal and indecisive, in 3.3% (10/300) PET/CT findings were false positive, while in 29.3% (88/300) a normal F-18 FDG pattern was present. Statistical analysis showed a sensitivity of 80.2% and a specificity of 89.8% for the contribution of PET/CT to the final diagnosis. CRP levels and WBC were not associated with PET/CT outcome. PET/CT let to new treatment in 24.0% (72/300), treatment change in 18.0% (54/300), no treatment change in 49.6% (149/300), and in 8.3% (25/300) no data was available. Our study demonstrates the utility of F-18 FDG PET/CT for source finding in FUO/IUO if other diagnostic tools fail.

Different Appearances of 3 Malignancies in 68Ga-PSMA-11 Versus 18F-FDG PET/CT.

ABSTRACT: Prostate-specific membrane antigen (PSMA) overexpression has been described in various malignancies. Hereby we present a case of a 69-year-old man simultaneously diagnosed with prostate cancer, esophageal adenocarcinoma, and HCC (hepatocellular carcinoma). 18F-FDG PET/CT showed pathological uptake in the esophageal adenocarcinoma and the primary prostate tumor, whereas 68Ga-PSMA-11 PET/CT performed for staging of the histopathologically confirmed prostate cancer revealed the primary tumor and significant uptake in the HCC. This finding is remarkable because the high physiological liver uptake of 68Ga-PSMA-11 may hamper the detection of small lesions.

18F-FDG PET/CT in the Hyperparathyroidism-Jaw-Tumor Syndrome.

ABSTRACT: Hyperparathyroidism-jaw-tumor syndrome (HPT-JTS) is a rare autosomal dominant disorder. A typical manifestation of HPT-JTS is the association of jaw-ossifying fibroma with primary hyperparathyroidism. Due to its rarity and diversity in its manifestations, it is a challenging diagnosis. A 33-year-old woman was referred due to painful swelling of the right maxilla suggestive of malignancy. The clinical presentations were not conclusive until she underwent F18-fluorodeoxyglucose positron emission tomography/computed tomography (F18-FDG PET/CT). F18-FDG PET/CT proved to be a useful tool to assist the clinicians in visualizing the "bigger picture" and, therefore all manifestation as pieces of "one puzzle."

Oligodendroglioma in 68Ga-PSMA-11 and 18F-Fluciclovine PET/CT.

ABSTRACT: Prostate cancer (PC) is one of the most common cancers affecting men worldwide, with a high recurrence rate after therapy. 68Ga-PSMA-11 and 18F-fluciclovine are PET imaging tracers for the detection of recurrence sites in PC patients. 68Ga-PSMA-11 is a membrane antigen overexpressed by tumor cells, whereas 18F-fluciclovine targets increased amino acid transporter in the membrane of cancer cells. We report a case of an 83-year-old man with known oligodendroglioma and biochemically recurrent PC who shows a high focal 68Ga-PSMA-11 and 18F-fluciclovine uptake in the brain.

Is there a place for FET PET in the initial evaluation of brain lesions with unknown significance?

PURPOSE: The aim of this study was to evaluate the clinical value of the use of O-(2-[(18)F]fluoroethyl)-L: -tyrosine (FET) positron emission tomography (PET)/computed tomography (CT) in patients of a neurological clinic for evaluation of brain lesions newly diagnosed by magnetic resonance imaging (MRI). METHODS: We evaluated 88 patients (44 women and 44 men) with a mean age of 50 +/- 19 years who were sent consecutively for evaluation of an intracerebral mass or lesion observed by MRI from 2006 to 2008. Hospitalization was necessary due to neurological clinical symptoms. Images were obtained by PET/CT 30 min after i.v. injection of 185 MBq FET. Coregistration with MRI was done by HERMES workstation. RESULTS: FET uptake above the cortical level was observed in 60 patients. Neurosurgery was performed in 60 patients (51 with FET-positive imaging); 36 high-grade and 19 low-grade tumours were verified histologically. The sensitivity of FET PET for high-grade tumours (WHO III-IV) was 94% in this setting. Among the low-grade brain tumours (WHO I-II) 13 of 19 were FET positive, which indicates a sensitivity of 68%. Five of ten (50%) astrocytomas I and II could not be visualized by FET. Histological data were not provided for 28 of 88 patients, so the diagnostic approach is based upon longitudinal observation. Radiological and/or clinical control was done at a median of 7 months later. Three patients (all FET positive) died a few months after the examination because of rapid progression of the malignant brain tumour. A malignant entity could be excluded in the other 25 patients. Considering the whole cohort of 88 patients, 43 patients with malignant tumour could be identified, including high-grade glioma, intracerebral lymphoma (n = 1) and metastasis (n = 3). The sensitivity of FET PET for detecting a malignant tumour entity was 93%. We observed two false-positive cases with postischaemic lesions. Remarkably, the two patients with cerebral gliomatosis were false-negative on FET PET imaging. The negative predictive value for a malignant entity was calculated to be 89%. CONCLUSION: Our results indicate a high sensitivity of FET PET for detecting high-grade glioma in patients with neurological symptoms and recently observed brain lesions by MRI. In the setting of evaluating new brain lesions of unknown significance via FET PET a negative image can encourage a wait and see strategy-of course in accordance with the clinical picture and morphological imaging.

Creation of a prevascularized site for cell transplantation in rats.

INTRODUCTION: Transplanted cells, especially islet cells, are likely to become apoptotic due to local hypoxia leading to graft dysfunction. Isolated pancreatic islet cells depend on the diffusion of oxygen from the surrounding tissue; therefore, access to sufficient oxygen supply is beneficial, particularly when microcapsules are used for immunoisolation in xenotransplantation. The aim of this study was to create a prevascularized site for cell transplantation in rats and test its effectiveness with microencapsulated HEK293 cells. METHODS: The combination of implantation of a foam dressing, vacuum-assisted wound closure (foam+VAC) and hyperbaric oxygenation (HBO) was used in 40 Sprague-Dawley rats. Blood flow and vascular endothelial growth factor (VEGF) levels were determined. Sodium cellulose sulphate (SCS)-microencapsulated HEK293 cells were xenotransplanted into the foam dressing in rats pre-treated with HBO, and angiogenesis and apoptosis were assessed. RESULTS: Vessel ingrowth and VEGF levels increased depending on the duration of HBO treatment. The area containing the foam was perfused significantly better in the experimental groups when compared to controls. Only a small amount of apoptosis occurs in SCS-microencapsulated HEK293 cells after xenotransplantation. CONCLUSION: As ischemia-damaged cells are likely to undergo cell death or loose functionality due to hypoxia, therefore leading to graft dysfunction, the combination foam+VAC and HBO might be a promising method to create a prevascularized site to achieve better results in xenogeneic cell transplantation.

The influence of physical activity on ghrelin and IGF-1/IGFBP-3 levels in children and adolescents with type 1 diabetes mellitus.

OBJECTIVES: The aim of the study was to determine the influence of regular physical activity on ghrelin and IGF-1/IGFBP-3 levels during a diabetes camp. METHODS: Twenty-eight children and adolescents (14 boys; mean age 12.1 yr) with type 1 diabetes mellitus (T1DM, mean duration of diabetes 4.8 yr) attending a 2-wk diabetes camp that features increased regular physical activities have been studied. Serum levels of ghrelin (total and acylated), growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor-bindng protein-3 (IGFBP-3) and insulin were measured in fasting state on day 1 and day 14. Improvement of metabolic control was documented by haemoglobin A1c (HbA1c). Glucose levels and insulin doses were determined daily. RESULTS: Mean insulin dosage decreased from 0.87 to 0.78 U/kg/d, mean HbA1c levels decreased from 8.6 to 8.3%, but the changes were not statistical. There was a significant decline in total ghrelin. IGFBP-3 and IGF-1 decreased also significantly. Total basal ghrelin was inversely related to the change in IGFBP-3. CONCLUSIONS: We hypothesize an association between ghrelin and metabolic control in T1DM. Higher ghrelin levels might be associated with poor metabolic control. The dynamic of IGFBP-3 levels appears to be under the influence of basal ghrelin concentrations in T1DM.

Systematic Assessment of the Adsorption of 99mTc-Radiopharmaceuticals onto Plastic Syringes.

The phenomenon of adsorption of several 99mTc-radiopharmaceuticals onto disposable syringes is common knowledge and can reach a level of up to 50%, with the result being inadequate dosing. The resulting underdosing has a substantial influence on the quality of imaging, especially in pediatric patients. Therefore, we aimed to establish a standardized in vitro assessment to investigate the adsorption of several 99mTc-radiopharmaceuticals on various brands of syringes. Methods: The 99mTc-radiopharmaceuticals were prepared according to manufacturer instructions. For the assessment, the disposable syringes (n = 3) were filled to one third of capacity with the 99mTc preparation and incubated for 30 min at room temperature. The syringes were emptied into evacuated vials, and the radioactivity of the syringes was measured before and after they were emptied. Furthermore, the dilution effect of 99mTc preparations was studied. We used 2 different brands of syringes and systematically examined 99mTc-pertechnetate, 99mTc-butedronate, 99mTc-oxidronate, 99mTc-medronate, 99mTc-tetrofosmin, 99mTc-sestamibi, 99mTc(V)-dimercaptosuccinic acid, and 99mTc-succimer. Additionally, 99mTc-succimer was retested with 5 brands of syringes. Results: 99mTc-pertechnetate, 99mTc-phosphonates, and 99mTc(V)-dimercaptosuccinic acid showed no significant adsorption. The measured radioactive retention of 2%-5% was equivalent to the determined dead volume. Using 99mTc-tetrofosmin, we found a slight but significant adsorption of 4%-7%. The 99mTc-sestamibi preparation showed a nonsignificant retention of 3%-5%. However, when the 99mTc-sestamibi was diluted 1:10 with saline, the adsorption rate increased to 9%-13%. 99mTc-succimer displayed different adsorption levels depending on the brand of syringe and the preparation technique. The adsorption of 99mTc-succimer, prepared from kits according to the instructions, did not exceed 15%. The 1:10 saline dilution of a 99mTc-succimer kit preparation, as well as an in-house preparation, demonstrated a radioactive syringe adsorption rate of more than 30%. Conclusion: The results revealed the significance of syringe adsorption of radiopharmaceuticals in the prevention of underdosing. Therefore, a quality assurance assessment is recommended before the introduction of new brands of plastic syringes or routine application of diluted or in-house radiopharmaceuticals.

Lymphoscintigraphy for Sentinel Lymph Node Biopsy in Breast Cancer: Do We Need a Delayed Image?

BACKGROUND: Sentinel lymph node biopsy has become a standard of care in the treatment of patients with early breast cancer, but clinical guidelines continue to be vague on details of the procedure. We were interested in the results of our 2-day protocol, which includes delayed lymphoscintigraphy at 18 h. METHODS: We reviewed the results of preoperative lymphoscintigrams in patients undergoing surgery for breast cancer. Lymphoscintigraphy was performed 2 h after periareolar injection of 4 × 37 MBq 99mTc nanocolloid (early lymphoscintigraphy) and 18 h following injection (delayed lymphoscintigraphy). The early results were compared with the late results. RESULTS: A total of 238 lymphoscintigraphies were performed in 232 patients (6 bilateral). At 2 h, ≥1 sentinel nodes were visualized in 154/238 (65%) cases; in 84 (35%), no sentinel node was visualized. Delayed lymphoscintigraphy visualized a sentinel node in 40 of 76 (53%) cases with no visualization at 2 h and failed to show a sentinel node in 36 (47%) of these cases (in 8 cases, no delayed lymphoscintigram was obtained). CONCLUSIONS: Delayed lymphoscintigraphy was useful in about 50% of the breast cancer patients in whom immediate scintigraphy failed to demonstrate a sentinel lymph node.

Periodontal treatment and vascular inflammation in patients with advanced peripheral arterial disease: A randomized controlled trial.

BACKGROUND AND AIMS: Observational studies support an association between periodontitis and cardiovascular diseases. The study objective was to assess vascular inflammation after periodontal treatment in patients with peripheral arterial disease. METHODS: Ninety patients with peripheral arterial disease (PAD) and severe periodontitis were enrolled in a randomized, controlled trial. Thirty patients underwent non-surgical periodontal therapy and received additional systemic antibiotics (PT1 group), while 30 patients received the same therapy without antibiotics (PT2 group). The remaining thirty patients did not receive periodontal therapy (CG, control group). The primary outcome of this treatment was a reduction in vascular inflammation three months after periodontal treatment as determined by 18F-FDG PET/CT values. Secondary outcomes were changes in the inflamed periodontal surface area (PISA) and other periodontal parameters, changes in vascular biomarkers, and adverse cardiovascular events. RESULTS: After three months of treatment, a significant improvement in periodontal health was observed in the treatment groups. However, no difference in the primary outcome in the aorta was observed in the three study groups (median target to background ratio follow-up/baseline, PT1 1.00; 95% CI 0.97-1.10, PT2 1.00; 95% CI 0.98-1.1, CG 1.1; 95% CI 0.99-1.1, p = 0.75). No significant differences were detected in most diseased segments and active segments. In addition, no differences were observed in 18F-FDG uptake in the carotid, iliac, femoral, and popliteal arteries. No differences with regard to relative changes in vascular biomarkers were noted, and no serious cardiovascular adverse events occurred. CONCLUSIONS: Periodontal treatment was effective and safe but did not reduce vascular inflammation in patients with PAD.