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Michael S Hofman - One of the best experts on this subject based on the ideXlab platform.
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protocol for the primary clinical trial a prospective multicentre cross sectional study of the additive diagnostic value of Gallium 68 prostate specific membrane antigen positron emission tomography computed tomography to multiparametric magnetic resonance imaging in the diagnostic setting for men being investigated for prostate cancer
BJUI, 2020Co-Authors: Amer Amin, Michael S Hofman, Declan G Murphy, Alexandar Blazevski, James Thompson, Matthijs J Scheltema, Nathan LawrentschukAbstract:OBJECTIVES: Primary objectives: To determine the additive value of Gallium-68 prostate-specific membrane antigen (PSMA) positron emission topography (PET)/computed tomography (CT) when combined with multiparametric magnetic resonance imaging (mpMRI) detecting clinically significant prostate cancer (csPCa) in men undergoing initial biopsy for suspicion of PCa, and to determine the proportion of men who could have avoided prostate biopsy with positive mpMRI (PI-RADS ≥3) but negative PSMA-PET/CT. Secondary objectives: To determine the proportion of men who had csPCa detected only by PSMA-PET/CT or only by systematic prostate biopsy; to compare index lesions by template biopsies vs targeted lesions identified on mpMRI or PSMA-PET/CT; to assess whether there may be health economic benefit or harm if PSMA-PET/CT is incorporated into the diagnostic algorithm; and to develop a nomogram which combines clinical, imaging and biomarker data to predict the likelihood of csPCa. PATIENTS AND METHODS: The PRIMARY trial is a multicentre, prospective, cross-sectional study that meets the criteria for level 1 evidence in diagnostic test evaluation. PRIMARY will investigate if a limited (pelvic-only) PSMA-PET/CT in combination with routine mpMRI can reliably discriminate men with csPCa from those without csPCa. We conducted a power calculation based on pilot data and will recruit up to 600 men who will undergo PSMA-PET/CT (the index test), mpMRI (standard test) and transperineal template + targeted (PSMA-PET/CT and/or mpMRI) biopsies (reference test). The conduct and reporting of the mpMRI and PSMA-PET/CT will be blinded to each other. RESULTS: The PRIMARY trial will measure and compare sensitivity, specificity, positive predictive value and negative predictive value of both mpMRI and PSMA-PET/CT vs targeted prostrate biopsy. The results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of csPCa. Furthermore, we will assess whether there is a health economic benefit in incorporating PSMA-PET/CT into the diagnostic algorithm. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of PSMA-PET/CT used in addition to mpMRI. It will establish if certain patients can avoid biopsy in the investigation of PCa.
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pet ct lung ventilation and perfusion scanning using galligas and Gallium 68 maa
Seminars in Nuclear Medicine, 2019Co-Authors: Pierreyves Le Roux, Rodney J Hicks, Shankar Siva, Michael S HofmanAbstract:Ventilation/Perfusion (V/Q) positron emission tomography computed tomography (PET/CT) is now possible by substituting Technetium-99m (99mTc) with Gallium-68 (68Ga), using the same carrier molecules as conventional V/Q imaging. Ventilation imaging can be performed with 68Ga-carbon nanoparticles using the same synthesis device as Technegas. Perfusion imaging can be performed with 68Ga-macroaggregated albumin. Similar physiological processes can therefore be evaluated by either V/Q SPECT/CT or PET/CT. However, V/Q PET/CT is inherently a superior technology for image acquisition, with higher sensitivity, higher spatial and temporal resolution, and superior quantitative capability, allowing more accurate delineation and quantification of regional lung function. Additional advantages include reduced acquisition time, respiratory-gated acquisition, and a lower impact on human resources. V/Q PET imaging offers an opportunity to improve the accuracy and utility of V/Q imaging in various pulmonary conditions. For pulmonary embolism, V/Q PET/CT scan may improve the diagnostic performance of the test owing to a better characterization of the pattern of defects and allow an accurate quantification of the extent of vascular obstruction. Establishing an accurate functional map of the regional ventilation and perfusion in the lungs may be relevant in many other clinical situations, including preoperative assessment of the lung cancer patients, radiotherapy planning, or presurgical evaluation of patients undergoing lung volume reduction surgery.
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a prospective randomized multicentre study of the impact of Gallium 68 prostate specific membrane antigen psma pet ct imaging for staging high risk prostate cancer prior to curative intent surgery or radiotherapy propsma study clinical trial protocol
BJUI, 2018Co-Authors: Michael S Hofman, Declan G Murphy, Scott Williams, Tatenda Nzenza, Alan Herschtal, Richard De Abreu LourencoAbstract:Background Accurate staging of patients with prostate cancer (PCa) is important for therapeutic decision-making. Relapse after surgery or radiotherapy of curative intent is not uncommon and, in part, represents a failure of staging with current diagnostic imaging techniques to detect disease spread. Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is a new whole-body scanning technique that enables visualization of PCa with high contrast. The hypotheses of this study are that: (i) PSMA-PET/CT has improved diagnostic performance compared with conventional imaging; (ii) PSMA-PET/CT should be used as a first-line diagnostic test for staging; (iii) the improved diagnostic performance of PSMA-PET/CT will result in significant management impact; and (iv) there are economic benefits if PSMA-PET/CT is incorporated into the management algorithm. Objectives and methods The proPSMA trial is a prospective, multicentre study in which patients with untreated high-risk PCa will be randomized to Gallium-68-PSMA-11 PET/CT or conventional imaging, consisting of CT of the abdomen/pelvis and bone scintigraphy with single-photon emission CT/CT. Patients eligible for inclusion are those with newly diagnosed PCa with select high-risk features, defined as International Society of Urological Pathology grade group ≥3 (primary Gleason grade 4, or any Gleason grade 5), prostate-specific antigen level ≥20 ng/mL or clinical stage ≥T3. Patients with negative, equivocal or oligometastatic disease on first line-imaging will cross over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT with that of conventional imaging for detecting nodal or distant metastatic disease. Histopathological, imaging and clinical follow-up at 6 months will define the primary endpoint according to a predefined scoring system. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross over, the cost of each imaging strategy, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer-term follow-up will also assess the prognostic value of a negative PSMA-PET/CT. Outcome and significance This trial will provide data to establish whether PSMA-PET/CT should replace conventional imaging in the primary staging of select high-risk localized PCa, or whether it should be used to provide incremental diagnostic information in selected cases.
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reduced ventilation perfusion v q mismatch following endobronchial valve insertion demonstrated by Gallium 68 v q photon emission tomography computed tomography
Respirology case reports, 2017Co-Authors: Paul Leong, Pierreyves Le Roux, Jason Callahan, Shankar Siva, Michael S Hofman, Daniel P SteinfortAbstract:Endobronchial valves (EBVs) are increasingly deployed in the management of severe emphysema. Initial studies focussed on volume reduction as the mechanism, with subsequent improvement in forced expiratory volume in 1 s (FEV1). More recent studies have emphasized importance of perfusion on predicting outcomes, though findings have been inconsistent. Gallium-68 ventilation-perfusion (V/Q) photon emission tomography (PET)/computed tomography (CT) is a novel imaging modality with advantages in spatial resolution, quantitation, and speed over conventional V/Q scintigraphy. We report a pilot case in which V/Q-PET/CT demonstrated discordant findings compared with quantitative CT analysis, and directed left lower lobe EBV placement. The patient experienced a significant improvement in 6-min walk distance (6MWD) without change in spirometry. Post-EBV V/Q-PET/CT demonstrated a marked decrease in unmatched (detrimental) V/Q areas and improvement in overall V/Q matching on post-EBV V/Q-PET/CT. These preliminary novel findings suggest that EBVs improve V/Q matching and may explain the observed functional improvements.
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improving diagnosis of tumor induced osteomalacia with Gallium 68 dotatate pet ct
The Journal of Clinical Endocrinology and Metabolism, 2013Co-Authors: Michael S Hofman, Roderick J Cliftonbligh, Emma L Duncan, Ie Wen Sim, David Darnell, Adele Clarkson, Tricia WongAbstract:Context: Tumor-induced osteomalacia (TIO) is a rarely diagnosed disorder presenting with bone pain, fractures, muscle weakness, and moderate-to-severe hypophosphatemia resulting from fibroblast growth factor 23-mediated renal phosphate wasting. Tumors secreting fibroblast growth factor 23 are often small and difficult to find with conventional imaging. Objective: We studied the utility of 68Ga-DOTA-octreotate (DOTATATE) somatostatin receptor positron emission tomography (PET)/computed tomography (CT) imaging in the diagnosis of TIO. Design and Setting: A multicenter case series was conducted at tertiary referral hospitals. Patients and Methods: Six patients with TIO diagnosed between 2003 and 2012 in Australia were referred for DOTATATE PET imaging. We reviewed the clinical history, biochemistry, imaging characteristics, histopathology, and clinical outcome of each patient. Results: Each case demonstrated delayed diagnosis despite severe symptoms. DOTATATE PET/CT imaging demonstrated high uptake and local...
Marlon Perera - One of the best experts on this subject based on the ideXlab platform.
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Gallium 68 prostate specific membrane antigen positron emission tomography in advanced prostate cancer updated diagnostic utility sensitivity specificity and distribution of prostate specific membrane antigen avid lesions a systematic review and meta
European Urology, 2020Co-Authors: Marlon Perera, Nathan Papa, Matthew J Roberts, Michael Williams, Cristian Udovicich, Ian Vela, Daniel Christidis, Damien M BoltonAbstract:Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard-of-care imaging modalities to improve the detection of metastatic disease in prostate cancer. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.
Kjell Oberg - One of the best experts on this subject based on the ideXlab platform.
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Gallium 68 somatostatin receptor pet ct is it time to replace 111 indium dtpa octreotide for patients with neuroendocrine tumors
Endocrine, 2012Co-Authors: Kjell ObergAbstract:Gallium-68 somatostatin receptor PET/CT : Is it time to replace (111)Indium DTPA octreotide for patients with neuroendocrine tumors?
Damien M Bolton - One of the best experts on this subject based on the ideXlab platform.
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Gallium 68 prostate specific membrane antigen positron emission tomography in advanced prostate cancer updated diagnostic utility sensitivity specificity and distribution of prostate specific membrane antigen avid lesions a systematic review and meta
European Urology, 2020Co-Authors: Marlon Perera, Nathan Papa, Matthew J Roberts, Michael Williams, Cristian Udovicich, Ian Vela, Daniel Christidis, Damien M BoltonAbstract:Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard-of-care imaging modalities to improve the detection of metastatic disease in prostate cancer. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.
Rodney J Hicks - One of the best experts on this subject based on the ideXlab platform.
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imaging somatostatin positive tumors with tyr3 octreotate octreotide conjugated to desferrioxamine b squaramide radiolabeled with either zirconium 89 or Gallium 68
Bioconjugate Chemistry, 2021Co-Authors: Asif Noor, Stacey E Rudd, Peter Roselt, Rodney J Hicks, Mohammad B Haskali, Michael Paul Wheatcroft, Jessica Van Zuylekom, Eddie Yan, Carleen CullinaneAbstract:Radiolabeled derivatives of Tyr3-octreotide and Tyr3-octreotate, synthetic analogues of the peptide hormone somatostatin, can be used for positron emission tomography (PET) imaging of somatostatin receptor expression in neuroendocrine tumors. In this work, a squaramide ester derivative of desferrioxamine B (H3DFOSq) was used attach either Tyr3-octreotide or Tyr3-octreotate to the metal binding ligand to give H3DFOSq-TIDE and H3DFOSq-TATE. These new peptide-H3DFOSq conjugates form stable complexes with either of the positron-emitting radionuclides Gallium-68 (t1/2 = 68 min) or zirconium-89 (t1/2 = 3.3 days). The new complexes were evaluated in an AR42J xenograft model that has endogenous expression of SSTR2. All four agents displayed good tumor uptake and produced high-quality PET images. For both radionuclides, the complexes formed with H3DFOSq-TATE performed better, with higher tumor uptake and retention than the complexes formed with H3DFOSq-TIDE. The versatile ligands presented here can be radiolabeled with either Gallium-68 or zirconium-89 at room temperature. The long radioactive half-life of zirconium-89 makes distribution of pre-synthesized tracers produced to certified standards feasible and could increase the number of clinical centers that can perform diagnostic PET imaging of neuroendocrine tumors.
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bivalent inhibitors of prostate specific membrane antigen conjugated to desferrioxamine b squaramide labeled with zirconium 89 or Gallium 68 for diagnostic imaging of prostate cancer
Journal of Medicinal Chemistry, 2020Co-Authors: Asif Noor, Stacey E Rudd, Peter Roselt, Rodney J Hicks, Jessica Van Zuylekom, Kelly Waldeck, Mohammad B Haskali, Michael Paul Wheatcroft, Carleen CullinaneAbstract:Prostate-specific membrane antigen (PSMA) is a carboxypeptidase that is overexpressed in prostate cancer and is an excellent candidate for targeted diagnostic imaging and therapy. Lysine-ureido-glutamate inhibitors of PSMA radiolabeled with positron-emitting radionuclides can be used for diagnostic imaging with positron emission tomography (PET). A squaramide ester derivative of desferrioxamine B (H3DFOSq) was used to prepare four new agents with either one or two lysine-ureido-glutamate pharmacophores. The H3DFOSq ligand can be used to form stable complexes with either of the positron-emitting radionuclides Gallium-68 (t1/2 = 68 min) or zirconium-89 (t1/2 = 3.3 days). The complexes were evaluated in PSMA-positive xenograft mouse models. Bivalent inhibitors, where two pharmacophores are tethered to a single DFOSq ligand, have better tumor uptake than their monovalent analogues. The ligands presented here, which can be labeled with either Gallium-68 or zirconium-89, have the potential to increase the number of clinical sites that can perform diagnostic PET imaging.
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pet ct lung ventilation and perfusion scanning using galligas and Gallium 68 maa
Seminars in Nuclear Medicine, 2019Co-Authors: Pierreyves Le Roux, Rodney J Hicks, Shankar Siva, Michael S HofmanAbstract:Ventilation/Perfusion (V/Q) positron emission tomography computed tomography (PET/CT) is now possible by substituting Technetium-99m (99mTc) with Gallium-68 (68Ga), using the same carrier molecules as conventional V/Q imaging. Ventilation imaging can be performed with 68Ga-carbon nanoparticles using the same synthesis device as Technegas. Perfusion imaging can be performed with 68Ga-macroaggregated albumin. Similar physiological processes can therefore be evaluated by either V/Q SPECT/CT or PET/CT. However, V/Q PET/CT is inherently a superior technology for image acquisition, with higher sensitivity, higher spatial and temporal resolution, and superior quantitative capability, allowing more accurate delineation and quantification of regional lung function. Additional advantages include reduced acquisition time, respiratory-gated acquisition, and a lower impact on human resources. V/Q PET imaging offers an opportunity to improve the accuracy and utility of V/Q imaging in various pulmonary conditions. For pulmonary embolism, V/Q PET/CT scan may improve the diagnostic performance of the test owing to a better characterization of the pattern of defects and allow an accurate quantification of the extent of vascular obstruction. Establishing an accurate functional map of the regional ventilation and perfusion in the lungs may be relevant in many other clinical situations, including preoperative assessment of the lung cancer patients, radiotherapy planning, or presurgical evaluation of patients undergoing lung volume reduction surgery.
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Gallium 68 complex of a macrobicyclic cage amine chelator tethered to two integrin targeting peptides for diagnostic tumor imaging
Bioconjugate Chemistry, 2011Co-Authors: Michelle T, Peter Roselt, Rodney J Hicks, Oliver C Neels, Delphine Denoyer, John A Karas, Denis B Scanlon, Jonathan M White, Paul S DonnellyAbstract:Tumor-targeting peptides radiolabeled with positron-emitting (68)Ga are promising candidates as new noninvasive diagnostic agents for positron emission tomography (PET). The targeting peptides are tethered to a chelator that forms a stable coordination complex with Ga(3+) that is inert to dissociation of Ga(3+)in vivo. Metal complexes of macrobicyclic hexaamine "sarcophagine" (sar = 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) ligands exhibit remarkable stability as a result of the encapsulating nature of the cage amine ligand. A Ga(3+) sarcophagine complex, [Ga-(1-NH(3)-8-NH(2)-sar)](4+), has been characterized using X-ray crystallography, demonstrating that Ga(3+) is coordinated to six nitrogen atoms in a distorted octahedral complex. A bifunctional derivative of (NH(2))(2)sar, possessing two aliphatic linkers with carboxylic acid functional groups has been attached to two cyclic-RGD peptides that target the α(v)β(3) integrin receptor that is overexpressed in some types of tumor tissue. This dimeric species can be radiolabeled with (68)Ga(3+) in >98% radiochemical yield and (68)Ga(3+) does not dissociate from the ligand in the presence of transferrin, an endogenous protein with high affinity for Ga(3+). Biodistribution and micro-PET imaging studies in tumor-bearing mice indicate that the tracer accumulates specifically in tumors with high integrin expression. The high tumor uptake is coupled with low nonspecific uptake and clearance predominantly through the kidneys resulting in high-quality PET images in animal models.
