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Simple Summary: Hypoxia is a phenomenon common in cervical cancer. Both the presence and function of CAFs are upregulated in a hypoxic environment. A key factor in the physiological response to hypoxia is hypoxia-inducible factor-1alpha (HIF-1 α). We hypothesized that [68Ga]Ga-FAPI PET may be used as an indirect tracer for mapping hypoxia by correlating the image findings to pathological analysis of HIF-1 α expression. The maximum and mean standardized uptake value (SUVmax and SUVmean) and FAPI tumor volume (FAPI-TV) were documented. There was uptake of tracer in the pelvis (cervix region) in all patients studied. All patients had lymph node metastases, while only six patients had distant visceral or skeletal metastases. The average FAPI-TV for patients with additional sites of metastases was higher than those without. Immunohistochemistry revealed varying intensities of HIF-1 α expression in all tested samples. The presence of skeletal metastasis was correlated to the HIF-1⍺ staining (percentage distribution). Furthermore, the FAPI-TV was a better predictor of metastatic disease than the SUVmax. Hypoxia leads to changes in tumor microenvironment (upregulated CAFs) with resultant aggressiveness. A key factor in the physiological response to hypoxia is hypoxia-inducible factor-1alpha (HIF-1 α). [68Ga]Ga-FAPI PET imaging has been demonstrated in various cancer types. We hypothesized that [68Ga]Ga-FAPI PET may be used as an indirect tracer for mapping hypoxia by correlating the image findings to pathological analysis of HIF-1 α expression. The [68Ga]Ga-FAPI PET/CT scans of women with cancer of the cervix were reviewed and the maximum and mean standardized uptake value (SUVmax and SUVmean) and FAPI tumor volume (FAPI-TV) were documented. Correlation analysis was performed between PET-derived parameters and immunohistochemical staining as well as between PET-derived parameters and the presence of metastasis. Ten women were included. All patients demonstrated tracer uptake in the primary site or region of the primary. All patients had lymph node metastases while only six patients had distant visceral or skeletal metastases. The mean SUVmax, SUVmean, and FAPI-TV was 18.89, 6.88, and 195.66 cm3, respectively. The average FAPI-TV for patients with additional sites of metastases was higher than those without. Immunohistochemistry revealed varying intensities of HIF-1 α expression in all tested samples. There was a positive correlation between the presence of skeletal metastases and staining for HIF-1 α   (r = 0.80 ; p = 0.017) . The presence of skeletal metastasis was correlated to the HIF-1⍺ staining (percentage distribution). Furthermore, the FAPI-TV was a better predictor of metastatic disease than the SUVmax. [ABSTRACT FROM AUTHOR]

Purpose: Actinium-225-labeled prostate-specific membrane antigen ([225Ac]Ac-PSMA-617) is safe and effective in the treatment of metastatic castration-resistant prostate cancer (mCRPC). No study has specifically assessed its safety in patients with extensive skeletal metastases of mCRPC. We aimed to investigate the hematologic toxicity and efficacy of [225Ac]Ac-PSMA-617 therapy in patients with extensive skeletal metastases of mCRPC. Methods: We retrospectively reviewed the medical record of patients treated with [225Ac]Ac-PSMA-617 for mCRPC. We included patients with a superscan pattern of skeletal metastases and those with 20 or more multifocal sites of skeletal metastases on baseline [68 Ga]Ga-PSMA-11 PET/CT. We reviewed the levels of hemoglobin, white blood cell (WBC), and platelet prior to each cycle of treatment and determined the presence of impaired bone marrow function at baseline and the grade of toxicity in the hematologic parameters induced by treatment. We evaluated the predictors of hematologic toxicity using binary logistic regression analysis. We also determined the presence of renal dysfunction before or during treatment. We assessed response to treatment using prostate-specific antigen response and the progression-free survival (PFS) and overall survival (OS). Results: A total of 106 patients were included. Skeletal metastasis was in the superscan pattern in 34 patients (32.1%) and multifocal in 72 patients (67.9%). The median treatment cycle was 4 (range = 1–9). Ninety-eight patients (92.5%) had abnormal baseline hematologic parameters. One patient had grade 4 thrombocytopenia. Grade 3 anemia, leukopenia, and thrombocytopenia were seen in 1 (0.9%), 3 (2.8%), and 2 (1.9%) patients, respectively. Age, the number of treatment cycles, and the presence of renal dysfunction were significant predictors of hematologic toxicity. Eighty-five patients (80.2%) achieved PSA response. The median PFS and OS of the study population were 14:00 (95%CI: 8.15–19.86) months and 15.0 (95%CI: 12.8–17.2) months, respectively. Conclusions: [225Ac]Ac-PSMA-617 induces a good anti-tumor effect in about 80% of patients with extensive skeletal metastases of mCRPC with a rare incidence of severe hematologic toxicity. Age, number of treatment cycles, and the presence of renal dysfunction were significant risk factors for hematologic toxicity of [225Ac]Ac-PSMA-617 therapy. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to determine the correlation of [68Ga]Ga-NODAGAZOL uptake in atherosclerotic plaques and the cardiovascular risk profile of patients imaged with positron emission tomography (PET), wherein quantification of uptake was determined by atherosclerotic plaque maximum target-to-background ratio (TBRmax). We also correlated uptake with a history of cardiovascular events. Methods: We included patients who underwent PET/CT imaging post-injection of [68Ga] Ga-NODAGAZOL. We documented the number of atherosclerotic plaques found in the major arteries on CT and the cardiovascular risks in each patient. We quantified the intensity of tracer uptake in atherosclerotic plaque in the major arteries using the maximum standardized uptake value (SUVmax). The SUVmax of the most tracer-avid plaque was documented as representative of the individual arterial bed. We determined background vascular tracer activity using the mean standardized uptake value (SUVmean) obtained from the lumen of the superior vena cava. The maximum target-to-background ratio (TBRmax) was calculated as a ratio of the SUVmax to the SUVmean. The TBRmax was correlated to the number of atherogenic risk factors and history of cardiovascular events. Results: Thirty-four patients (M: F 31:3; mean age ± SD: 63 ± 10.01 years) with ≥ 2 cardiovascular risk factors were included. Statistically significant correlation between TBRmax and the number of cardiovascular risk factors was noted in the right carotid (r = 0.50; p < 0.05); left carotid (r = 0. 649; p < 0.05); ascending aorta (r = 0.375; p < 0.05); aortic arch (r = 0.483; p < 0.05); thoracic aorta (r = 0.644; p < 0.05); left femoral (r = 0.552; p < 0.05) and right femoral arteries (r = 0.533; p < 0.05). TBRmax also demonstrated a positive correlation to history of cardiovascular event in the right carotid (U = 26.00; p < 0.05); left carotid (U = 11.00; p < 0.05); ascending aorta (U = 49.00; p < 0.05); aortic arch (U = 37.00; p < 0.05); thoracic aorta (U = 16.00; p < 0.05); left common iliac (U = 49.500; p < 0.05), right common iliac (U = 43.00; p < 0.05), left femoral (U = 40.500; p < 0.05) and right femoral (U = 37.500; p < 0.05). Conclusion: In this cohort of patients, a positive correlation was noted between atherosclerotic plaque uptake of [68Ga]Ga-NODAGAZOL and the number of atherogenic risk factors which translates to the risk of atherosclerosis and cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Prostate adenocarcinoma (PCa) is a leading cause of mortality. Black males with high-risk PCa have a poorer prognosis compared to white males. Patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 and 2 PCa have little potential for metastases post radical prostatectomy. 68Gallium prostate specific membrane antigen (68Ga-PSMA) PET/CT imaging for metastatic PCa is superior to conventional imaging in staging high-risk PCa. No strong evidence is available to support imaging low-risk patients. We aimed to evaluate the value of 68Ga-PSMA PET/CT in black and white South African (BSA and WSA) males with GG1 and 2 PCa at initial staging. We evaluated 25 WSA and 123 BSA males. The image findings were correlated with prostate specific antigen (PSA). PSA levels significantly correlated with both primary tumor and whole-body PSMA-tumor volume (PSMA-TV) and were higher in BSA males. No differences were noted in the occurrence of metastases; however, PSA, seminal vesicle invasion and black race predicted metastases. Our findings suggest higher PSMA expression and tumor burden in BSA with histologically low-risk PCa, and future research with immunohistochemistry evaluation will be essential to confirm these findings. [ABSTRACT FROM AUTHOR]

Hypoxia in cervical cancer has been associated with a poor prognosis. Over the years 68Ga labelled nitroimidazoles have been studied and have shown improved kinetics. We present our initial experience of hypoxia Positron Emission Tomography (PET) imaging in cervical cancer with 68Ga-Nitroimidazole derivative and the correlation with 18F-FDG PET/CT and immunohistochemistry. Twenty women with cervical cancer underwent both 18F-FDG and 68Ga-Nitroimidazole PET/CT imaging. Dual-point imaging was performed for 68Ga-Nitroimidazole PET. Immunohistochemical analysis was performed with hypoxia inducible factor-1α (HIF-1α). We documented SUVmax, SUVmean of the primary lesions as well as tumor to muscle ratio (TMR), tumor to blood (TBR), metabolic tumor volume (MTV) and hypoxic tumor volume (HTV). There was no significant difference in the uptake of 68Ga-Nitroimidazole between early and delayed imaging. Twelve patients had uptake on 68Ga-Nitroimidazole PET. Ten patients demonstrated varying intensities of HIF-1α expression and six of these also had uptake on 68Ga-Nitroimidazole PET. We found a strong negative correlation between HTV and immunohistochemical staining (r = −0.660; p = 0.019). There was no correlation between uptake on PET imaging and immunohistochemical analysis with HIF-1α. Two-thirds of the patients demonstrated hypoxia on 68Ga-Nitroimidazole PET imaging. [ABSTRACT FROM AUTHOR]

People living with human immunodeficiency virus (PLHIV) have excess risk of atherosclerotic cardiovascular disease (ASCVD). Arterial inflammation is the hallmark of atherogenesis and its complications. In this study we aimed to perform a head-to-head comparison of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) and Gallium-68 pentixafor positron emission tomography/computed tomography [68Ga]Ga-pentixafor PET/CT for quantification of arterial inflammation in PLHIV. We prospectively recruited human immunodeficiency virus (HIV)-infected patients to undergo [18F]FDG PET/CT and [68Ga]Ga-pentixafor PET/CT within two weeks of each other. We quantified the levels of arterial tracer uptake on both scans using maximum standardized uptake value (SUVmax) and target–background ratio. We used Bland and Altman plots to measure the level of agreement between tracer quantification parameters obtained on both scans. A total of 12 patients were included with a mean age of 44.67 ± 7.62 years. The mean duration of HIV infection and mean CD+ T-cell count of the study population were 71.08 ± 37 months and 522.17 ± 260.33 cells/µL, respectively. We found a high level of agreement in the quantification variables obtained using [18F]FDG PET and [68Ga]Ga-pentixafor PET. There is a good level of agreement in the arterial tracer quantification variables obtained using [18F]FDG PET/CT and [68Ga]Ga-pentixafor PET/CT in PLHIV. This suggests that [68Ga]Ga-pentixafor may be applied in the place of [18F]FDG PET/CT for the quantification of arterial inflammation. [ABSTRACT FROM AUTHOR]