13 research outputs found

    [68ga]ga-pentixafor for pet imaging of vascular expression of cxcr-4 as a marker of arterial inflammation in hiv-infected patients : a comparison with18f[fdg] pet imaging

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    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.http://www.mdpi.com/journal/biomoleculespm2021Nuclear Medicin

    A prospective investigation of tumor hypoxia imaging with 68Ga-nitroimidazole PET/CT in patients with carcinoma of the cervix uteri and comparison with 18F-FDG PET/CT : correlation with immunohistochemistry

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    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-1 (HIF-1 ). 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-1 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-1 . Two-thirds of the patients demonstrated hypoxia on 68Ga-Nitroimidazole PET imaging.https://www.mdpi.com/journal/jcmam2022Nuclear Medicin

    225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: a pilot study

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    Background: A remarkable therapeutic efficacy has been demonstrated with 225Ac-prostate-specific membrane antigen (PSMA)-617 in heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC) patients. We report our experience with 225Ac-PSMA-617 therapy in chemotherapy-naïve patients with advanced metastatic prostate carcinoma. Methods: Seventeen patients with advanced prostate cancer were selected for treatment with 225Ac-PSMA-617 in 2-month intervals, with initial activity of 8 MBq, then de-escalation to 7 MBq, 6 MBq or 4 MBq in cases of good response. In one patient, activity was escalated to 13 MBq in the third cycle. Fourteen patients had three treatment cycles administered, while in three patients treatment was discontinued after two cycles due to good response. Six out of 17 patients received additional treatments after the third cycle. Prostate-specific antigen (PSA) was measured every 4 weeks for PSA response assessment. 68Ga-PSMA-PET/CT was used for functional response assessment before each subsequent treatment cycle. Serial full blood count, renal function test, and liver function were obtained to determine treatment-related side effects. Results: Good antitumor activity assessed by serum PSA level and 68Ga-PSMA-PET/CT was seen in 16/17 patients. In 14/17 patients, PSA decline ≥90% was seen after treatment, including seven patients with undetectable serum PSA following two (2/7) or three cycles (5/7) cycles of 225Ac-PSMA-617. Fifteen of 17 patients had a > 50% decline in lesions avidity for tracer on 68Ga-PSMA-PET/CT including 11 patients with complete resolution (PET-negative and either stable sclerosis on CT for bone or resolution of lymph node metastases) of all metastatic lesions. Grade 1/2 xerostomia was seen in all patients, and none was severe enough to lead to discontinuation of treatment. One patient had with extensive bone marrow metastases and a background anemia developed a grade 3 anemia while another patient with solitary kidney and pre-treatment grade 3 renal failure developed grade 4 renal toxicity following treatment. The group presented with significant palliation of bone pain and reduced toxicity to salivary glands due to de-escalation. Conclusions: 225Ac-PSMA-617 RLT of chemotherapy-naïve patients with advanced metastatic prostate carcinoma led to a ≥ 90% decline in serum PSA in 82% of patients including 41% of patients with undetectable serum PSA who remained in remission 12 months after therapy. The remarkable therapeutic efficacy reported in this study could be achieved with reduced toxicity to salivary glands due to de-escalation of administered activities in subsequent treatment cycles. This necessitates further exploration for informing clinical practice and clinical trial design.JRC.G.I.5-Advanced Nuclear Knowledg

    Correlation between PSA response and response assessment with 68Ga-PSMA-11 PET/CT-derived metabolic parameters in patients treated with 225Ac-PSMA-617 for metastatic prostate carcinoma

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    PSA decline ≥50% is the validated criteria for assessing response to treatment in patients with prostate carcinoma. 68Ga-PSMA-11 PET/CT-derived metabolic parameters such as SUVmax, SUVmean, whole-body tumor volume (PSMA-TV) and whole-body total lesion PSMA (TL-PSMA) are increasingly being reported as metrics for response assessment. We herein compare the response assessment using PSA decline versus 68Ga-PSMA-11 PET/CT-derived metabolic parameters in patients treated with 225Ac-PSMA-617 for metastatic castration-resistant prostate carcinoma (mCRPC).JRC.G.I.5-Advanced Nuclear Knowledg

    225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer : a pilot study

    No full text
    BACKGROUND : A remarkable therapeutic efficacy has been demonstrated with 225Ac-prostate-specific membrane antigen (PSMA)- 617 in heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC) patients.We report our experience with 225Ac- PSMA-617 therapy in chemotherapy-naïve patients with advanced metastatic prostate carcinoma. METHODS : Seventeen patients with advanced prostate cancer were selected for treatment with 225Ac-PSMA-617 in 2-month intervals, with initial activity of 8 MBq, then de-escalation to 7 MBq, 6 MBq or 4 MBq in cases of good response. In one patient, activity was escalated to 13 MBq in the third cycle. Fourteen patients had three treatment cycles administered, while in three patients treatment was discontinued after two cycles due to good response. Six out of 17 patients received additional treatments after the third cycle. Prostate-specific antigen (PSA) was measured every 4 weeks for PSA response assessment. 68Ga- PSMA-PET/CT was used for functional response assessment before each subsequent treatment cycle. Serial full blood count, renal function test, and liver function were obtained to determine treatment-related side effects. RESULTS : Good antitumor activity assessed by serum PSA level and 68Ga-PSMA-PET/CT was seen in 16/17 patients. In 14/17 patients, PSA decline ≥90% was seen after treatment, including seven patients with undetectable serum PSA following two (2/7) or three cycles (5/7) cycles of 225Ac-PSMA-617. Fifteen of 17 patients had a > 50% decline in lesions avidity for tracer on 68Ga- PSMA-PET/CT including 11 patients with complete resolution (PET-negative and either stable sclerosis on CT for bone or resolution of lymph node metastases) of all metastatic lesions. Grade 1/2 xerostomia was seen in all patients, and none was severe enough to lead to discontinuation of treatment. One patient had with extensive bone marrow metastases and a background anemia developed a grade 3 anemia while another patient with solitary kidney and pre-treatment grade 3 renal failure developed grade 4 renal toxicity following treatment. The group presented with significant palliation of bone pain and reduced toxicity to salivary glands due to de-escalation. CONCLUSIONS : 225Ac-PSMA-617 RLTof chemotherapy-naïve patients with advanced metastatic prostate carcinoma led to a ≥ 90% decline in serum PSA in 82% of patients including 41% of patients with undetectable serum PSA who remained in remission 12 months after therapy. The remarkable therapeutic efficacy reported in this study could be achieved with reduced toxicity to salivary glands due to de-escalation of administered activities in subsequent treatment cycles. This necessitates further exploration for informing clinical practice and clinical trial design.http://link.springer.com/journal/259am2020Nuclear Medicin

    Predictors of Overall and Disease-Free Survival in Metastatic Castration-Resistant Prostate Cancer Patients Receiving 225Ac-PSMA-617 Radioligand Therapy

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    Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with 225Ac-PSMA-617, identifying variables predictive for overall survival (OS) and progression-free survival (PFS) after 225Ac-PSMA-617 treatment. Methods: 225Ac-PSMA-617 was administered to patients who had metastatic castration-resistant prostate carcinoma and who had exhausted available therapy options for their disease. Full blood count, glomerular filtration rate, and liver function test were obtained at baseline and on follow-up for evaluation of toxicity. 68Ga-PSMA PET/CT was obtained at baseline, before every treatment cycle, and on follow-up for selection of patients for treatment, to determine the activity of the treatment agent to be administered, and for response assessment. Serial prostate-specific antigen (PSA) was obtained for PSA response assessment. Results: Seventy-three men (mean age, 69 y; range, 45–85 y) with metastatic castration-resistant prostate carcinoma were treated with 210 cycles of 225Ac-PSMA-617. In 70% of patients, a PSA decline of greater than or equal to 50% was obtained; 82% of patients had any PSA decline. In 29% of patients, all lesions on 68Ga-PSMA PET resolved in response to treatment. During follow-up, 23 patients experienced disease progression, whereas 13 patients died from their disease. The estimated median PFS and OS were 15.2 mo (95% CI, 13.1–17.4) and 18 mo (95% CI, 16.2–19.9), respectively. In univariate analyses, factors such as baseline PSA, any PSA decline, PSA decline of greater than or equal to 50%, prior chemotherapy, prior radiation therapy, and baseline hemoglobin level were associated with longer PFS and OS (all Ps < 0.05). In multivariate analyses, there was a negative association between prior 177Lu-PSMA therapy and PFS, and a positive association between PSA decline of greater or equal to 50% and PFS. Only a PSA decline of greater than or equal to 50% remained significantly associated with OS on multivariate analyses. Xerostomia was seen in 85% of patients but was not severe enough to warrant discontinuing treatment. Anemia was seen in 27 patients; no patients had grade IV bone marrow toxicity. Renal failure of grade III or IV was seen in 5 patients with baseline renal impairment. Conclusion: In this study, a PSA decline of greater than or equal to 50% after treatment with 225Ac-PSMA-617 was proven by multivariate analyses to be significantly associated with OS and PFS. Furthermore, previous 177Lu-PSMA treatment was negatively associated with PFS in both univariate and multivariate analyses.JRC.G.I.5-Advanced Nuclear Knowledg
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