European Journal of Nuclear Medicine and Molecular Imaging
The authors regret that some texts are missing in the original article. The original article has ... more The authors regret that some texts are missing in the original article. The original article has been corrected. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This article is part of the Topical Collection on Erratum.
INTRODUCTION AND OBJECTIVE:PSMA is established for TRT with either monoclonal antibodies (mAb) or... more INTRODUCTION AND OBJECTIVE:PSMA is established for TRT with either monoclonal antibodies (mAb) or small molecule ligands. The molecular weight, pharmacokinetics, and biodistribution of mAb vs ligan...
PURPOSEMultiple approaches with [Ga68]-DOTATATE, a somatostatin analog PET radiotracer, have demo... more PURPOSEMultiple approaches with [Ga68]-DOTATATE, a somatostatin analog PET radiotracer, have demonstrated clinical utility in evaluation of meningioma but have not been compared directly. Our purpose was to compare diagnostic performance of three approaches to quantitative brain [68Ga]-DOTATATE PET/MRI analysis in patients with suspected meningioma recurrence and to establish the optimal diagnostic threshold for each method.METHODSPatients with suspected meningioma were imaged prospectively with [68Ga]-DOTATATE brain PET/MRI. Lesions were classified as meningiomas and post-treatment change (PTC), based on pathology findings and follow up MRI appearance. Lesions were reclassified using the following methods: absolute SUV threshold (SUV), SUV ratio (SUVR) to superior sagittal sinus (SSS) (SUVRsss), and SUVR to the pituitary gland (SUVRpit). Diagnostic performance of the three methods was compared using contingency tables and McNemar’s test. Previously published pre-determined threshol...
INTRODUCTION AND OBJECTIVE:177Lu-PSMA is a promising investigational treatment for men with mCRPC... more INTRODUCTION AND OBJECTIVE:177Lu-PSMA is a promising investigational treatment for men with mCRPC. Optimal selection and biomarkers remain to be defined. Here, we report a combined analysis of men ...
Abstract: Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest sou... more Abstract: Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest source of cancer-related mortality in males of African ancestry (MoAA). Interestingly, this has been shown to be associated with single nucleotide polymorphisms around regions 2 and 3 of the 8q24 human chromosomal region. The non-protein coding gene locus Plasmacytoma Variant Translocation 1 (PVT1) is located at 8q24 and is overexpressed in PCa and, therefore, is also a candidate biomarker to explain the well-known disparity in this group. PVT1 has at least 12 exons that make separate transcripts which may have different functions, all of which are at present unknown in PCa. Our aim was to determine if any PVT1 transcripts play a role in aggressiveness and racial disparity in PCa. We used a panel of seven PCa cell lines including three derived from MoAA. Ribonucleic acid extraction, complementary deoxyribonucleic acid synthesis, and quantitative polymerase chain reaction (qPCR) were perform...
Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest source of can... more Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest source of cancer-related mortality in males of African ancestry (MoAA). Interestingly, this has been shown to be associated with single nucleotide polymorphisms around regions 2 and 3 of the 8q24 human chromosomal region. The non-protein coding gene locus Plasmacytoma Variant Translocation 1 (PVT1) is located at 8q24 and is overexpressed in PCa and, therefore, is also a candidate biomarker to explain the well-known disparity in this group. PVT1 has at least 12 exons that make separate transcripts which may have different functions, all of which are at present unknown in PCa. Our aim was to determine if any PVT1 transcripts play a role in aggressiveness and racial disparity in PCa. We used a panel of seven PCa cell lines including three derived from MoAA. Ribonucleic acid extraction, complementary deoxyribonucleic acid synthesis, and quantitative polymerase chain reaction (qPCR) were performed to eval...
1. Assistant Member, Molecular Imaging and Therapy Service, Department of Radiology, Memorial Slo... more 1. Assistant Member, Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center 2. Radiology Resident, Department of Diagnostic Radiology, Metrohealth Medical Center, Case Western Reserve University 3. Partner and the Global Provide Practice Leader, Health & Life Sciences Practice, Oliver Wyman 4. Professor of Radiology, Division of Nuclear Medicine, Department of Radiology, University of Iowa Hospitals and Clinics
120 Background: Elevated CTC counts are associated with a poor prognosis in men with mCRPC. PSMA ... more 120 Background: Elevated CTC counts are associated with a poor prognosis in men with mCRPC. PSMA targeted radionuclide therapy has been associated with decline in CTC count, but it remains unclear whether this effect results from radionuclide-induced cytotoxicity. J591 was engineered to have antibody-dependent cytotoxicity. A subset of patients was observed to have CTC count decline following imaging with 111In-J591, so a prospective study was launched to test the hypothesis that “naked” J591 leads to CTC count decline. Methods: In a Simon 2-stage dose de-escalation study, men with progressive mCRPC and unfavorable CTC count (CellSearch > 4) received a single dose of J591. Initial dose cohort 300 mg with de-escalation to 20 mg. CTC count was re-assessed 4, 8, and 12 weeks following therapy along with PSA and standard imaging. An optional PSMA PET was included prior to treatment. The primary endpoint was proportion of subjects with conversion to favorable CTC count ( < 5 CTCs/7...
Highlights • PSMA PET/MRI has a higher true positive rate and sensitivity than mpMRI in patients ... more Highlights • PSMA PET/MRI has a higher true positive rate and sensitivity than mpMRI in patients with biochemically recurrent prostate cancer.• The true positive rate for PSMA PET/MRI was significantly greater in patients who were post prostatectomy for primary treatment.• 40% of patients with a PSA value less than 0.2 ng/mL had a positive PSMA PET/MRI read compared to 9% on MRI.
BACKGROUND Prostate Cancer Working Group 3 and FDA guidelines recommend a standardized approach t... more BACKGROUND Prostate Cancer Working Group 3 and FDA guidelines recommend a standardized approach to pain assessment in preapproval trials. No prior trial has examined pain palliation of Radium-223 using standard dosing and contemporary PRO pain-assessment tools. METHODS In this multicenter phase II trial, patients with Brief Pain Inventory (BPI) ≥3 were eligible for Radium-223 per its label. Primary endpoint was a 30% decrease in BPI Worst Pain from baseline to Week 8, sustained at Week 12 without escalation of medication on the World Health Organization (WHO) analgesic ladder. Secondary endpoints included changes in Brief Fatigue Inventory (BFI) Worst fatigue and BPI pain interference. If six of 27 subjects (22%) met the primary endpoint, the trial would expand by another 36 subjects. RESULTS Twenty-nine subjects were accrued. Nine of 29 (31%) subjects met the primary endpoint, with 21 (72%) evaluable for the primary endpoint. Among responders: median worst pain declined 62% (range 36-100) at Week 8 and 63% (range 38-100) at Week 12; median reduction of pain interference with general activity and sleep at Week 12 was 62% (range 18-100) and 53% (range 8-100) respectively; median reduction in worst fatigue of 45% (range 10-85) at Week 12. CONCLUSIONS In the first prospective trial using standard Ra-223 doses, contemporary pain endpoints and PRO collection tools, Ra-223 palliated pain, reduced fatigue, and improved pain interference. The pain response rate easily exceeded the requirements for expansion to the second phase, but the trial was closed due to slow accrual.
18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) underperforms in detecting prostate... more 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) underperforms in detecting prostate cancer (PCa) due to inherent characteristics of primary and metastatic tumors, including relatively low rate of glucose utilization. Consequently, alternate PCa PET imaging agents targeting other aspects of PCa cell biology have been developed for clinical practice. The most common dedicated PET imaging tracers include 68Ga/18F prostate-specific membrane antigen (PSMA), 11C-Choline, and 18F-fluciclovine (Axumin™). This review will describe how these agents target specific inherent characteristics of PCa and explore the current literature for these agents for both primary and recurrent PCa, comparing the advantages and limitations of each tracer. Both 11C-Choline and 18F-Fluciclovine PET have been shown to detect nodal and osseous disease at higher rates compared to FDG-PET but offer no additional benefit in detecting prostate disease, especially in primary staging. As a result, PSMA PET, specifically 68Ga-PSMA-11, has emerged as a key imaging option for both primary and recurrent cancer. PSMA PET may be more sensitive than MRI at the local level and more sensitive than 11C-Choline and 18F-Fluciclovine PET for distant disease. Furthermore, compared to 11C-Choline and 18F-Fluciclovine PET, 68Ga-PSMA-11 PET has higher detection rates at low PSA levels (<2 ng/dL). With improved delineation of disease, PSMA imaging has influenced treatment planning; radiation fields can be narrowed, and patients with isolated or oligo-metastatic disease can be spared systemic therapy. The retrospective nature of many of the studies describing these PCa imaging modalities complicates their assessment and comparison.
PURPOSE Postoperative PET/MRI with [68Ga]-DOTATATE can differentiate residual meningioma from pos... more PURPOSE Postoperative PET/MRI with [68Ga]-DOTATATE can differentiate residual meningioma from postsurgical change, aid in target delineation, and portend a more favorable dosimetry with decreased PTV and organ-at-risk dose. Our purpose was to demonstrate utility of DOTATATE PET/MR for radiosurgical treatment (RT) response assessment in meningiomas. METHODS Patients underwent postoperative radiation treatment planning using DOTATATE PET/MRI as part of our IRB-approved prospective trial. Both DOTATATE PET and gadolinium-enhanced T1 weighted MR imaging were incorporated in RT-planning. All patients underwent follow-up DOTATATE PET/MRI at 6-12 months following completion of radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVR) of lesion/ superior sagittal sinus SUV were obtained. RANO criteria were applied to determine significance of change in size. Statistical analyses were performed using paired t-tests. RESULTS 13 patients (15% WHO-I, 54% WHO-II, 23% WH...
Urologic Oncology: Seminars and Original Investigations, 2020
BACKGROUND Docetaxel remains a standard of care for metatsatic castration resistant porstate canc... more BACKGROUND Docetaxel remains a standard of care for metatsatic castration resistant porstate cancer (mCRPC) and has radiosensitizing properties. The dose limiting toxicity (DLT) of radioimmunotherapy is myelosuppression; dose fractionation of 177Lu-J591 allows similar administered doses with less toxicity. This study (NCT00916123) was designed to determine the safety, DLT, and maximum tolerated dose of fractionated 177Lu-J591 administered concurrently with standard docetaxel. METHODS Men with progressive mCRPC received docetaxel 75 mg/m2 every 3 weeks with escalating 2 fractionated doses of 177Lu-J591 (1.48 GBq/m2 up to max of 2.96 GBq/m2) with cycle 3. Cycle 4 of docetaxel was planned 6 weeks after cycle 3 to allow for recovery from 177Lu-J591-associated hematologic toxicity. DLT was defined as delay in docetaxel >3 weeks, prolonged myelosuppression or need for >2 platelet transfusions, febrile neutropenia, or grade ≥3 nonhematological toxicity following 177Lu-J591. PSA was assessed prior to each cycle and serial computed tomography (CT) and bone scan were performed. RESULTS Fifteen men with progressive mCRPC received dose-escalated targeted radionuclide therapy in 4 cohorts up to the highest planned dose (2.96 GBq/m2). No DLT was seen at any dose level. Grade 4 neutropenia without fever occurred in 8 (53.5%) and thromboytopenia in 2 (13.3%), with 2 receiving prophylactic platelet transfusion. No grade ≥3 nonhematological toxicity was observed. 11 (73.3%) had >50% PSA decline, with 78.6% having favorable circulating tumor cell counts after 177Lu-J591. All patients had targeting of known sites of disease by planar 177Lu-J591 imaging. CONCLUSION The combination of 177Lu-J591 delivered as a single fractionated cycle with docetaxel/prednisone is feasible in patients with mCRPC. Without preselection for prostate-specific membrane antigen, accurate targeting of known sites of disease and a strong preliminary efficacy signal was observed.
45 Background: We performed the 1st dose-escalation study of PSMA-targeted radionuclide therapy w... more 45 Background: We performed the 1st dose-escalation study of PSMA-targeted radionuclide therapy with 177Lu-PSMA-617. Using dose-fractionation, we intended to deliver a dose-intense regimen designed to minimize radioresistance due to repopulation. Radionuclide therapy may be able to treat symptoms due to tumor and therefore may be associated with improvement in PRO. Methods: Inclusion: progressive mCRPC following potent AR-pathway inhibitor (ARPI, e.g. abi/enza) and taxane (or unfit/refuse chemo) without limit of # prior therapies, adequate organ function, ECOG performance status 0-2, without preselection for PSMA expression. Treatment was a single cycle of fractionated dose 177Lu-PSMA-617 on D1 and D15 (7.4 to 22 GBq in phase 1; 22.2 GBq in phase 2). PRO tools included FACT-P and BPI-SF at baseline and follow up. Results: 44 men with median age 69 (range 55-91), median PSA 182.97 (range 0.89-5541) were treated. 93% with bone, 45% nodal, 18% lung, 9% liver, 9% other visceral metastas...
11081 Background: PSMA is nearly universally expressed by PC, upregulated with increased grade an... more 11081 Background: PSMA is nearly universally expressed by PC, upregulated with increased grade and castration-resistance. Evidence points towards PSMA expression as a downstream cellular biomarker of androgen receptor (AR) activity and non-invasive measurement of PSMA expression has recently been demonstrated to be a novel biomarker of AR activity. Methods: Planar gamma camera images following radiolabeled J591 (111In-J591 or 177Lu-J591) were semi-quantitatively scored using 2 methods by 2 independent radiologists blinded to outcome.A 5-point visual score (VS) of 0 - 4+ was assigned. Tissue Targeting Index (TTI), a novel metric designed to semi-quantitatively score images was calculated using the ratio of lesion count density (corrected for background) to whole body count density, with maximum (TTImax) and mean (TTIave) scores recorded. Follow up tabulating subsequent therapies and overall survival (OS) was recorded and imaging scores were associated with OS using Cox regression ana...
Patients with brain tumors treated with radiotherapy (RT) often develop cognitive dysfunction, an... more Patients with brain tumors treated with radiotherapy (RT) often develop cognitive dysfunction, and recent studies suggest that the apolipoprotein (APOE) ϵ-4 allele may influence cognitive outcome. The ϵ-4 allele promotes beta (β) amyloid deposition in the cortex, and preliminary evidence suggests that RT may be associated with β-amyloid deposition. In this pilot study, we assessed neuropsychological functions and β-amyloid retention using 18F-florbetaben PET in a subset of brain tumor patients who participated in our study of APOE polymorphisms and cognitive functions. Twenty glioma patients treated with conformal RT ± chemotherapy participated in the study: 6 were APOE ϵ-4 carriers and 14 were non-ϵ-4 carriers. Patients completed a neuropsychological reevaluation and brain MRI and 18F-florbetaben PET scans. The results of Wilcoxon rank sums test comparisons between prior and current assessments showed a significant decline in selective attention (Brief Test of Attention, p=0.018), and a near-significant decline in verbal learning (Hopkins Verbal Learning Test-Learning, p=0.07). Comparisons between assessments by APOE status showed a significant decline in attention and working memory (WAIS-III digits forward, p=0.028 and digits backward, p=0.032) among APOE ϵ-4 carriers. Comparisons of PET regional standard uptake value ratios (SUVRs) showed near-significant differences for the medial temporal cortex (p=0.069) and the putamen (p=0.069), with non-ϵ-4 carriers having higher SUVRs. The findings suggest that glioma patients may experience progressive worsening in attention and executive functions several years after treatment with RT ± chemotherapy, and that the APOE ϵ-4 allele may moderate cognitive decline. Note: This abstract was not presented at the conference. Citation Format: Denise Correa, Maria Kryza-Lacombe, Xiaosun Zhou, Raymond Baser, Brad Beattie, Zodina Beiene, Irene Orlow, John Humm, Lisa DeAngelis, Wolfgang Weber, Joseph Osborne. A pilot study of neuropsychological functions, APOE, and amyloid imaging in patients with gliomas [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B39.
European Journal of Nuclear Medicine and Molecular Imaging
The authors regret that some texts are missing in the original article. The original article has ... more The authors regret that some texts are missing in the original article. The original article has been corrected. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This article is part of the Topical Collection on Erratum.
INTRODUCTION AND OBJECTIVE:PSMA is established for TRT with either monoclonal antibodies (mAb) or... more INTRODUCTION AND OBJECTIVE:PSMA is established for TRT with either monoclonal antibodies (mAb) or small molecule ligands. The molecular weight, pharmacokinetics, and biodistribution of mAb vs ligan...
PURPOSEMultiple approaches with [Ga68]-DOTATATE, a somatostatin analog PET radiotracer, have demo... more PURPOSEMultiple approaches with [Ga68]-DOTATATE, a somatostatin analog PET radiotracer, have demonstrated clinical utility in evaluation of meningioma but have not been compared directly. Our purpose was to compare diagnostic performance of three approaches to quantitative brain [68Ga]-DOTATATE PET/MRI analysis in patients with suspected meningioma recurrence and to establish the optimal diagnostic threshold for each method.METHODSPatients with suspected meningioma were imaged prospectively with [68Ga]-DOTATATE brain PET/MRI. Lesions were classified as meningiomas and post-treatment change (PTC), based on pathology findings and follow up MRI appearance. Lesions were reclassified using the following methods: absolute SUV threshold (SUV), SUV ratio (SUVR) to superior sagittal sinus (SSS) (SUVRsss), and SUVR to the pituitary gland (SUVRpit). Diagnostic performance of the three methods was compared using contingency tables and McNemar’s test. Previously published pre-determined threshol...
INTRODUCTION AND OBJECTIVE:177Lu-PSMA is a promising investigational treatment for men with mCRPC... more INTRODUCTION AND OBJECTIVE:177Lu-PSMA is a promising investigational treatment for men with mCRPC. Optimal selection and biomarkers remain to be defined. Here, we report a combined analysis of men ...
Abstract: Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest sou... more Abstract: Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest source of cancer-related mortality in males of African ancestry (MoAA). Interestingly, this has been shown to be associated with single nucleotide polymorphisms around regions 2 and 3 of the 8q24 human chromosomal region. The non-protein coding gene locus Plasmacytoma Variant Translocation 1 (PVT1) is located at 8q24 and is overexpressed in PCa and, therefore, is also a candidate biomarker to explain the well-known disparity in this group. PVT1 has at least 12 exons that make separate transcripts which may have different functions, all of which are at present unknown in PCa. Our aim was to determine if any PVT1 transcripts play a role in aggressiveness and racial disparity in PCa. We used a panel of seven PCa cell lines including three derived from MoAA. Ribonucleic acid extraction, complementary deoxyribonucleic acid synthesis, and quantitative polymerase chain reaction (qPCR) were perform...
Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest source of can... more Prostate cancer (PCa) is the most commonly diagnosed cancer as well as the greatest source of cancer-related mortality in males of African ancestry (MoAA). Interestingly, this has been shown to be associated with single nucleotide polymorphisms around regions 2 and 3 of the 8q24 human chromosomal region. The non-protein coding gene locus Plasmacytoma Variant Translocation 1 (PVT1) is located at 8q24 and is overexpressed in PCa and, therefore, is also a candidate biomarker to explain the well-known disparity in this group. PVT1 has at least 12 exons that make separate transcripts which may have different functions, all of which are at present unknown in PCa. Our aim was to determine if any PVT1 transcripts play a role in aggressiveness and racial disparity in PCa. We used a panel of seven PCa cell lines including three derived from MoAA. Ribonucleic acid extraction, complementary deoxyribonucleic acid synthesis, and quantitative polymerase chain reaction (qPCR) were performed to eval...
1. Assistant Member, Molecular Imaging and Therapy Service, Department of Radiology, Memorial Slo... more 1. Assistant Member, Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center 2. Radiology Resident, Department of Diagnostic Radiology, Metrohealth Medical Center, Case Western Reserve University 3. Partner and the Global Provide Practice Leader, Health & Life Sciences Practice, Oliver Wyman 4. Professor of Radiology, Division of Nuclear Medicine, Department of Radiology, University of Iowa Hospitals and Clinics
120 Background: Elevated CTC counts are associated with a poor prognosis in men with mCRPC. PSMA ... more 120 Background: Elevated CTC counts are associated with a poor prognosis in men with mCRPC. PSMA targeted radionuclide therapy has been associated with decline in CTC count, but it remains unclear whether this effect results from radionuclide-induced cytotoxicity. J591 was engineered to have antibody-dependent cytotoxicity. A subset of patients was observed to have CTC count decline following imaging with 111In-J591, so a prospective study was launched to test the hypothesis that “naked” J591 leads to CTC count decline. Methods: In a Simon 2-stage dose de-escalation study, men with progressive mCRPC and unfavorable CTC count (CellSearch > 4) received a single dose of J591. Initial dose cohort 300 mg with de-escalation to 20 mg. CTC count was re-assessed 4, 8, and 12 weeks following therapy along with PSA and standard imaging. An optional PSMA PET was included prior to treatment. The primary endpoint was proportion of subjects with conversion to favorable CTC count ( < 5 CTCs/7...
Highlights • PSMA PET/MRI has a higher true positive rate and sensitivity than mpMRI in patients ... more Highlights • PSMA PET/MRI has a higher true positive rate and sensitivity than mpMRI in patients with biochemically recurrent prostate cancer.• The true positive rate for PSMA PET/MRI was significantly greater in patients who were post prostatectomy for primary treatment.• 40% of patients with a PSA value less than 0.2 ng/mL had a positive PSMA PET/MRI read compared to 9% on MRI.
BACKGROUND Prostate Cancer Working Group 3 and FDA guidelines recommend a standardized approach t... more BACKGROUND Prostate Cancer Working Group 3 and FDA guidelines recommend a standardized approach to pain assessment in preapproval trials. No prior trial has examined pain palliation of Radium-223 using standard dosing and contemporary PRO pain-assessment tools. METHODS In this multicenter phase II trial, patients with Brief Pain Inventory (BPI) ≥3 were eligible for Radium-223 per its label. Primary endpoint was a 30% decrease in BPI Worst Pain from baseline to Week 8, sustained at Week 12 without escalation of medication on the World Health Organization (WHO) analgesic ladder. Secondary endpoints included changes in Brief Fatigue Inventory (BFI) Worst fatigue and BPI pain interference. If six of 27 subjects (22%) met the primary endpoint, the trial would expand by another 36 subjects. RESULTS Twenty-nine subjects were accrued. Nine of 29 (31%) subjects met the primary endpoint, with 21 (72%) evaluable for the primary endpoint. Among responders: median worst pain declined 62% (range 36-100) at Week 8 and 63% (range 38-100) at Week 12; median reduction of pain interference with general activity and sleep at Week 12 was 62% (range 18-100) and 53% (range 8-100) respectively; median reduction in worst fatigue of 45% (range 10-85) at Week 12. CONCLUSIONS In the first prospective trial using standard Ra-223 doses, contemporary pain endpoints and PRO collection tools, Ra-223 palliated pain, reduced fatigue, and improved pain interference. The pain response rate easily exceeded the requirements for expansion to the second phase, but the trial was closed due to slow accrual.
18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) underperforms in detecting prostate... more 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) underperforms in detecting prostate cancer (PCa) due to inherent characteristics of primary and metastatic tumors, including relatively low rate of glucose utilization. Consequently, alternate PCa PET imaging agents targeting other aspects of PCa cell biology have been developed for clinical practice. The most common dedicated PET imaging tracers include 68Ga/18F prostate-specific membrane antigen (PSMA), 11C-Choline, and 18F-fluciclovine (Axumin™). This review will describe how these agents target specific inherent characteristics of PCa and explore the current literature for these agents for both primary and recurrent PCa, comparing the advantages and limitations of each tracer. Both 11C-Choline and 18F-Fluciclovine PET have been shown to detect nodal and osseous disease at higher rates compared to FDG-PET but offer no additional benefit in detecting prostate disease, especially in primary staging. As a result, PSMA PET, specifically 68Ga-PSMA-11, has emerged as a key imaging option for both primary and recurrent cancer. PSMA PET may be more sensitive than MRI at the local level and more sensitive than 11C-Choline and 18F-Fluciclovine PET for distant disease. Furthermore, compared to 11C-Choline and 18F-Fluciclovine PET, 68Ga-PSMA-11 PET has higher detection rates at low PSA levels (<2 ng/dL). With improved delineation of disease, PSMA imaging has influenced treatment planning; radiation fields can be narrowed, and patients with isolated or oligo-metastatic disease can be spared systemic therapy. The retrospective nature of many of the studies describing these PCa imaging modalities complicates their assessment and comparison.
PURPOSE Postoperative PET/MRI with [68Ga]-DOTATATE can differentiate residual meningioma from pos... more PURPOSE Postoperative PET/MRI with [68Ga]-DOTATATE can differentiate residual meningioma from postsurgical change, aid in target delineation, and portend a more favorable dosimetry with decreased PTV and organ-at-risk dose. Our purpose was to demonstrate utility of DOTATATE PET/MR for radiosurgical treatment (RT) response assessment in meningiomas. METHODS Patients underwent postoperative radiation treatment planning using DOTATATE PET/MRI as part of our IRB-approved prospective trial. Both DOTATATE PET and gadolinium-enhanced T1 weighted MR imaging were incorporated in RT-planning. All patients underwent follow-up DOTATATE PET/MRI at 6-12 months following completion of radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVR) of lesion/ superior sagittal sinus SUV were obtained. RANO criteria were applied to determine significance of change in size. Statistical analyses were performed using paired t-tests. RESULTS 13 patients (15% WHO-I, 54% WHO-II, 23% WH...
Urologic Oncology: Seminars and Original Investigations, 2020
BACKGROUND Docetaxel remains a standard of care for metatsatic castration resistant porstate canc... more BACKGROUND Docetaxel remains a standard of care for metatsatic castration resistant porstate cancer (mCRPC) and has radiosensitizing properties. The dose limiting toxicity (DLT) of radioimmunotherapy is myelosuppression; dose fractionation of 177Lu-J591 allows similar administered doses with less toxicity. This study (NCT00916123) was designed to determine the safety, DLT, and maximum tolerated dose of fractionated 177Lu-J591 administered concurrently with standard docetaxel. METHODS Men with progressive mCRPC received docetaxel 75 mg/m2 every 3 weeks with escalating 2 fractionated doses of 177Lu-J591 (1.48 GBq/m2 up to max of 2.96 GBq/m2) with cycle 3. Cycle 4 of docetaxel was planned 6 weeks after cycle 3 to allow for recovery from 177Lu-J591-associated hematologic toxicity. DLT was defined as delay in docetaxel >3 weeks, prolonged myelosuppression or need for >2 platelet transfusions, febrile neutropenia, or grade ≥3 nonhematological toxicity following 177Lu-J591. PSA was assessed prior to each cycle and serial computed tomography (CT) and bone scan were performed. RESULTS Fifteen men with progressive mCRPC received dose-escalated targeted radionuclide therapy in 4 cohorts up to the highest planned dose (2.96 GBq/m2). No DLT was seen at any dose level. Grade 4 neutropenia without fever occurred in 8 (53.5%) and thromboytopenia in 2 (13.3%), with 2 receiving prophylactic platelet transfusion. No grade ≥3 nonhematological toxicity was observed. 11 (73.3%) had >50% PSA decline, with 78.6% having favorable circulating tumor cell counts after 177Lu-J591. All patients had targeting of known sites of disease by planar 177Lu-J591 imaging. CONCLUSION The combination of 177Lu-J591 delivered as a single fractionated cycle with docetaxel/prednisone is feasible in patients with mCRPC. Without preselection for prostate-specific membrane antigen, accurate targeting of known sites of disease and a strong preliminary efficacy signal was observed.
45 Background: We performed the 1st dose-escalation study of PSMA-targeted radionuclide therapy w... more 45 Background: We performed the 1st dose-escalation study of PSMA-targeted radionuclide therapy with 177Lu-PSMA-617. Using dose-fractionation, we intended to deliver a dose-intense regimen designed to minimize radioresistance due to repopulation. Radionuclide therapy may be able to treat symptoms due to tumor and therefore may be associated with improvement in PRO. Methods: Inclusion: progressive mCRPC following potent AR-pathway inhibitor (ARPI, e.g. abi/enza) and taxane (or unfit/refuse chemo) without limit of # prior therapies, adequate organ function, ECOG performance status 0-2, without preselection for PSMA expression. Treatment was a single cycle of fractionated dose 177Lu-PSMA-617 on D1 and D15 (7.4 to 22 GBq in phase 1; 22.2 GBq in phase 2). PRO tools included FACT-P and BPI-SF at baseline and follow up. Results: 44 men with median age 69 (range 55-91), median PSA 182.97 (range 0.89-5541) were treated. 93% with bone, 45% nodal, 18% lung, 9% liver, 9% other visceral metastas...
11081 Background: PSMA is nearly universally expressed by PC, upregulated with increased grade an... more 11081 Background: PSMA is nearly universally expressed by PC, upregulated with increased grade and castration-resistance. Evidence points towards PSMA expression as a downstream cellular biomarker of androgen receptor (AR) activity and non-invasive measurement of PSMA expression has recently been demonstrated to be a novel biomarker of AR activity. Methods: Planar gamma camera images following radiolabeled J591 (111In-J591 or 177Lu-J591) were semi-quantitatively scored using 2 methods by 2 independent radiologists blinded to outcome.A 5-point visual score (VS) of 0 - 4+ was assigned. Tissue Targeting Index (TTI), a novel metric designed to semi-quantitatively score images was calculated using the ratio of lesion count density (corrected for background) to whole body count density, with maximum (TTImax) and mean (TTIave) scores recorded. Follow up tabulating subsequent therapies and overall survival (OS) was recorded and imaging scores were associated with OS using Cox regression ana...
Patients with brain tumors treated with radiotherapy (RT) often develop cognitive dysfunction, an... more Patients with brain tumors treated with radiotherapy (RT) often develop cognitive dysfunction, and recent studies suggest that the apolipoprotein (APOE) ϵ-4 allele may influence cognitive outcome. The ϵ-4 allele promotes beta (β) amyloid deposition in the cortex, and preliminary evidence suggests that RT may be associated with β-amyloid deposition. In this pilot study, we assessed neuropsychological functions and β-amyloid retention using 18F-florbetaben PET in a subset of brain tumor patients who participated in our study of APOE polymorphisms and cognitive functions. Twenty glioma patients treated with conformal RT ± chemotherapy participated in the study: 6 were APOE ϵ-4 carriers and 14 were non-ϵ-4 carriers. Patients completed a neuropsychological reevaluation and brain MRI and 18F-florbetaben PET scans. The results of Wilcoxon rank sums test comparisons between prior and current assessments showed a significant decline in selective attention (Brief Test of Attention, p=0.018), and a near-significant decline in verbal learning (Hopkins Verbal Learning Test-Learning, p=0.07). Comparisons between assessments by APOE status showed a significant decline in attention and working memory (WAIS-III digits forward, p=0.028 and digits backward, p=0.032) among APOE ϵ-4 carriers. Comparisons of PET regional standard uptake value ratios (SUVRs) showed near-significant differences for the medial temporal cortex (p=0.069) and the putamen (p=0.069), with non-ϵ-4 carriers having higher SUVRs. The findings suggest that glioma patients may experience progressive worsening in attention and executive functions several years after treatment with RT ± chemotherapy, and that the APOE ϵ-4 allele may moderate cognitive decline. Note: This abstract was not presented at the conference. Citation Format: Denise Correa, Maria Kryza-Lacombe, Xiaosun Zhou, Raymond Baser, Brad Beattie, Zodina Beiene, Irene Orlow, John Humm, Lisa DeAngelis, Wolfgang Weber, Joseph Osborne. A pilot study of neuropsychological functions, APOE, and amyloid imaging in patients with gliomas [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B39.
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