Sir Peter MacCallum Department of Oncology - Research Publications
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ItemUtility of 68Ga-DOTA-Exendin-4 positron emission tomography-computed tomography imaging in distinguishing between insulinoma and nesidioblastosis in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia(WILEY, 2021-10)BACKGROUND: Because management is very different, it is important to differentiate between small focal insulinomas and diffuse pancreatic dysplasia (nesidioblastosis) in patients with confirmed endogenous hyperinsulinaemic hypoglycaemia (EHH). Most insulinomas highly express glucagon-like peptide-1 receptors enabling positron emission tomography-computed tomography imaging with its radiolabelled analogue; 68 Ga-DOTA-Exendin-4 (Exendin). AIM: To determine: (i) the utility of Exendin in EHH patients in a clinical setting; and (ii) whether the degree of Exendin uptake differentiates non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) from post-gastric bypass hypoglycaemia (PGBH). METHODS: This retrospective study reviewed the clinical, biochemistry and prior imaging findings in confirmed EHH patients referred for Exendin. Accuracy of Exendin was based on surgical findings and treatment outcomes. Finally, average Exendin uptake (SUVmax) of five PGBH studies was compared with the SUVmax of a key NIPHS case report. RESULTS: Twenty of 25 consecutive patients had confirmed EHH. Exendin located insulinomas in eight of nine patients enabling successful surgical excision with rapid and durable cure. Exendin correctly identified diffuse nesidioblastosis in two of three cases requiring partial pancreatectomy for hypoglycaemia control. All three relapsed within 1.7 years with one needing completion pancreatectomy. Establishing the cause in the remainder relied on other investigations, clinical correlation and response to empirical treatment. Finally, Exendin SUVmax could not distinguish between NIPHS and PGBH. CONCLUSION: In EHH patients, Exendin accurately identifies the site of insulinoma and thereby differentiates it from nesidioblastosis but negative findings should not be ignored. Exendin is unlikely to differentiate between normal pancreatic uptake, NIPHS and PGBH.
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ItemPSMA targeting in metastatic castration-resistant prostate cancer: where are we and where are we going?(SAGE PUBLICATIONS LTD, 2021-10)Prostate-specific membrane antigen (PSMA) is highly expressed on the membrane of most prostate cancer cells and to a lesser extent in normal tissues. Many vectors targeting this protein have been created over the past decade and numerous clinical studies have positively demonstrated the tolerance and efficacy of radiolabeled prostate-specific membrane antigen ligands for PSMA radioligand therapy (PRLT). Preliminary results are encouraging that PRLT will become an important addition to the current therapeutic options in a number of settings. Improvement in radiopharmaceutical targeting and combination with other oncological agents are under investigation to further improve its therapeutic efficacy. These encouraging results have led to the development of other therapies using PSMA as a target, such as PSMA-targeted chimeric antigen receptor T-cells, PSMA-targeted antibody drug conjugates, and PSMA-targeted bi-specific T-cell-directed therapy. This narrative review details the current state and advancements in prostate-specific membrane antigen targeting in prostate cancer treatment.
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ItemIntense focal pituitary FDG uptake due to intravascular large B-cell lymphoma in pyrexia of unknown origin(WILEY-BLACKWELL, 2016-11)
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ItemVoxel-wise correlation of positron emission tomography/computed tomography with multiparametric magnetic resonance imaging and histology of the prostate using a sophisticated registration framework(WILEY, 2019-06)OBJECTIVES: To develop a registration framework for correlating positron emission tomography/computed tomography (PET/CT) images with multiparametric magnetic resonance imaging (mpMRI) and histology of the prostate, thereby enabling voxel-wise analysis of imaging parameters. PATIENTS AND METHODS: In this prospective proof-of-concept study, nine patients scheduled for radical prostatectomy underwent mpMRI and PET/CT imaging before surgery. One had PET imaging using 18 F-fluoromethylcholine, five using 68 Ga-labelled prostate-specific membrane antigen (PSMA)-HBED-CC (PMSA-11), and three using a trial 68 Ga-labelled THP-PSMA tracer. PET/CT data were co-registered with mpMRI via the CT scan and an in vivo three-dimensional T2-weighted (T2w) MRI, and then co-registered with ground truth histology data using ex vivo MRI of the prostate specimen. Maximum and mean standardised uptake values (SUVmax and SUVmean ) were extracted from PET data using tumour annotations from histology, and Kolmogorov-Smirnov tests were used to compare between tumour- and benign-voxel values. Correlation analysis was performed between mpMRI and PET SUV tumour voxel values using Pearson's correlation coefficient and R2 statistics. RESULTS: PET/CT data from all nine patients were successfully registered with mpMRI and histology data. SUVmax and SUVmean ranged from 2.21 to 12.11 and 1.08 to 4.21, respectively. All patients showed the PET SUV values in benign and tumour voxels were from statistically different distributions. Correlation analysis showed no consistent trend between the T2w or apparent diffusion coefficient values and PET SUV. However, parameters from dynamic contrast-enhanced (DCE) MRI including the maximum enhancement, volume transfer constant (Ktrans ), and the initial area under the contrast agent concentration curve for the first 60 s after injection (iAUGC60), showed consistent positive correlations with PET SUV. Furthermore, R2* values from blood oxygen level-dependent (BOLD) MRI showed consistent negative correlations with PET SUV-voxel values. CONCLUSION: We have developed a novel framework for registering and correlating PET/CT data at a voxel-level with mpMRI and histology. Despite registration uncertainties, perfusion and oxygenation parameters from DCE MRI and BOLD imaging showed correlations with PET SUV. Further analysis will be performed on a larger patient cohort to quantify these proof-of-concept findings. Improved understanding of the correlation between mpMRI and PET will provide supportive information for focal therapy planning of the prostate.
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ItemA pilot study of cardiopulmonary exercise testing and cardiac stress positron emission tomography before major non-cardiac surgery(WILEY, 2018-12)Cardiac events are a common cause of peri-operative morbidity. Cardiopulmonary exercise testing can objectively assess risk, but it does not quantify myocardial ischaemia. With appropriate dietary preparation to suppress basal myocardial glucose uptake, positron emission tomography with 18 F-fluorodeoxyglucose can identify post-ischaemic myocardium, providing an attractive complement to exercise testing. We aimed to investigate the feasibility of this diagnostic algorithm. Patients referred for cardiopulmonary exercise testing before major cancer surgery were prospectively recruited. Exercise testing and positron emission tomography imaging were performed after a high fat-low carbohydrate meal. Protocol feasibility (primary end-point) included compliance with pre-test diet instructions and the completion of tests. Stress myocardial perfusion imaging was performed if either exercise testing or positron emission tomography was equivocal or positive for ischaemia. We recorded cardiac complications for 30 postoperative days. We enrolled 26 participants, 20 of whom completed protocol. Twenty-one participants proceeded to surgery: myocardial injury or infarction was diagnosed in three participants, two of whom had positive or equivocal positron emission tomography but negative myocardial perfusion imaging. We have shown that pre-operative cardiac positron emission tomography after cardiopulmonary exercise testing is feasible; protocol deviations were minor and did not affect image quality. Our findings warrant further investigation to compare the diagnostic utility of cardiac positron emission tomography imaging with standard pre-operative stress tests.
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ItemA 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(WILEY, 2018-11)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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ItemIntra-patient comparison of physiologic 68Ga-PSMA-11 and 18F-DCFPyL PET/CT uptake in ganglia in prostate cancer patients: a pictorial essay(BMC, 2021-04-16)BACKGROUND: Recent studies reported metabolic uptake in at least one of the evaluated ganglia in 98.5% of patients undergoing 68Ga -PSMA-11 and in 96.9% of patients undergoing 18F-DCFPyL PET/CT examination. We have observed different patterns of ganglion visualization with 18F-DCFPyL compared to 68Ga-PSMA-11. This includes more frequent visualization of cervical and sacral ganglia, which may be attributable to better imaging characteristics with 18F PET imaging. CASE PRESENTATION: This pictorial essay is to illustrate and compare, in the same patient, various representative cases of 68Ga-PSMA-11 and 18F-DCFPyL PET/CT uptake in ganglia at different anatomic locations, with different patterns and distribution of metabolic activity. CONCLUSION: Reading physicians should be aware of the frequently encountered and occasionally different physiologic uptake of 68Ga-PSMA-11 and 18F DCFPyL in different ganglia.
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ItemTechnical Note: Rapid multiexponential curve fitting algorithm for voxel-based targeted radionuclide dosimetry(WILEY, 2020-09)BACKGROUND: Dosimetry in nuclear medicine often relies on estimating pharmacokinetics based on sparse temporal data. As analysis methods move toward image-based three-dimensional computation, it becomes important to interpolate and extrapolate these data without requiring manual intervention; that is, in a manner that is highly efficient and reproducible. Iterative least-squares solvers are poorly suited to this task because of the computational overhead and potential to optimize to local minima without applying tight constraints at the outset. METHODOLOGY: This work describes a fully analytical method for solving three-phase exponential time-activity curves based on three measured time points in a manner that may be readily employed by image-based dosimetry tools. The methodology uses a series of conditional statements and a piecewise approach for solving exponential slope directly through measured values in most instances. The proposed algorithm is tested against a purpose-designed iterative fitting technique and linear piecewise method followed by single exponential in a cohort of ten patients receiving 177 Lu-DOTA-Octreotate therapy. RESULTS: Tri-exponential time-integrated values are shown to be comparable to previously published methods with an average difference between organs when computed at the voxel level of 9.8 ± 14.2% and -3.6 ± 10.4% compared to iterative and interpolated methods, respectively. Of the three methods, the proposed tri-exponential algorithm was most consistent when regional time-integrated activity was evaluated at both voxel- and whole-organ levels. For whole-body SPECT imaging, it is possible to compute 3D time-integrated activity maps in <5 min processing time. Furthermore, the technique is able to predictably and reproducibly handle artefactual measurements due to noise or spatial misalignment over multiple image times. CONCLUSIONS: An efficient, analytical algorithm for solving multiphase exponential pharmacokinetics is reported. The method may be readily incorporated into voxel-dose routines by combining with widely available image registration and radiation transport tools.
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ItemGallium-68 Ventilation/Perfusion PET-CT and CT Pulmonary Angiography for Pulmonary Embolism Diagnosis: An Interobserver Agreement Study(FRONTIERS MEDIA SA, 2021-02-16)Objectives: 68Ga Ventilation/Perfusion V/Q PET-CT is a promising imaging tool for pulmonary embolism diagnosis. However, no study has verified whether the interpretation is reproducible between different observers. The aim of this study was to assess the interobserver agreement in the interpretation of V/Q PET-CT for the diagnosis of acute PE, and to compare it to the interobserver agreement of CTPA interpretation. Methods: Twenty-four cancer patients with suspected acute PE underwent V/Q PET-CT and CTPA within 24 h as part of a prospective pilot study evaluating V/Q PET-CT for the management of patients with suspected PE. V/Q PET-CT and CTPA scans were reassessed independently by four nuclear medicine physicians and four radiologists, respectively. Physicians had different levels of expertise in reading V/Q scintigraphy and CTPA. Interpretation was blinded to the initial interpretation and any clinical information or imaging test result. For each modality, results were reported on a binary fashion. V/Q PET/CT scans were read as positive if there was at least one segmental or two subsegmental mismatched perfusion defects. CTPA scans were interpreted as positive if there was a constant intraluminal filling defect. Interobserver agreement was assessed by calculating kappa (κ) coefficients. Results: Out of the 24 V/Q PET-CT scans, the diagnostic conclusion was concordantly negative in 22 patients and concordantly positive in one patient. The remaining scan was interpreted as positive by one reader and negative by three readers. Out of the 24 CTPA scans, the diagnostic conclusion was concordantly negative in 16 and concordantly positive in one. Out of the seven remaining scans, PE was reported by one reader in four cases, by two readers in two cases, by three readers in one case. Most of discordant results on CTPA were related to clots reported on subsegmental arteries. Mean kappa coefficient was 0.79 for V/Q PET-CT interpretation and 0.39 for CTPA interpretation. Conclusions: Interobserver agreement in the interpretation of V/Q PET-CT for PE diagnosis was substantial (kappa 0.79) in a population with a low prevalence of significant PE. Agreement was lower with CTPA, mainly as a result of discrepancies at the level of the subsegmental arteries.