Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials

ABSTRACTWith a host of new antitubercular chemotherapeutics in development, methods to assess the activity of these agents beyond mouse efficacy are needed to prioritize combinations for clinical trials. Lesions inMycobacterium tuberculosis-infected rabbits are hypoxic, with histopathologic features that closely resemble those of human tuberculous lesions. Using [18F]2-fluoro-deoxy-d-glucose ([18F]FDG) positron emission tomography–computed tomography (PET-CT) imaging, we studied the dynamics of tuberculosis infection in rabbits, revealing an initial inflammatory response followed by a consolidative chronic disease. Five weeks after infection, as much as 23% of total lung volume was abnormal, but this was contained and to some extent reversed naturally by 9 weeks. During development of this chronic state, individual lesions in the same animal had very different fates, ranging from complete resolution to significant progression. Lesions that remained through the initial stage showed an increase in volume and tissue density over time by CT. Initiation of chemotherapy using either isoniazid (INH) or rifampin (RIF) during chronic infection reduced bacterial load with quantitative changes in [18F]FDG uptake, lesion density and total lesion volume measured by CT. The [18F]FDG PET uptake in lesions was significantly reduced with as little as 1 week of treatment, while the volume and density of lesions changed more slowly. The results from this study suggest that rabbits may be a useful surrogate species for evaluating novel chemotherapies and understanding changes in both PET and CT scans in human clinical trials.

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Immuno-Positron Emission Tomography with Zirconium-89-Labeled Monoclonal Antibodies in Oncology: What Can We Learn from Initial Clinical Trials?

Frontiers in Pharmacology ◽

10.3389/fphar.2016.00131 ◽

2016 ◽

Vol 7 ◽

Cited By ~ 79

Author(s):

Yvonne W. S. Jauw ◽

C. Willemien Menke-van der Houven van Oordt ◽

Otto S. Hoekstra ◽

N. Harry Hendrikse ◽

Danielle J. Vugts ◽

...

Keyword(s):

Positron Emission Tomography ◽

Clinical Trials ◽

Monoclonal Antibodies ◽

Emission Tomography ◽

Positron Emission

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Beyond the AJR: “Aggregated Tau Measured by Visual Interpretation of Flortaucipir Positron Emission Tomography and the Associated Risk of Clinical Progression of Mild Cognitive Impairment and Alzheimer Disease Results From 2 Phase III Clinical Trials”

American Journal of Roentgenology ◽

10.2214/ajr.21.26174 ◽

2021 ◽

Author(s):

Aaron Field ◽

Sterling C. Johnson

Keyword(s):

Positron Emission Tomography ◽

Clinical Trials ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Emission Tomography ◽

Phase Iii ◽

Visual Interpretation ◽

Clinical Progression ◽

Phase Iii Clinical Trials ◽

Positron Emission

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Positron Emission Tomography–Directed Therapy for Patients With Limited-Stage Diffuse Large B-Cell Lymphoma: Results of Intergroup National Clinical Trials Network Study S1001

Journal of Clinical Oncology ◽

10.1200/jco.20.00999 ◽

2020 ◽

Vol 38 (26) ◽

pp. 3003-3011 ◽

Cited By ~ 1

Author(s):

Daniel O. Persky ◽

Hongli Li ◽

Deborah M. Stephens ◽

Steven I. Park ◽

Nancy L. Bartlett ◽

...

Keyword(s):

Positron Emission Tomography ◽

Clinical Trials ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Emission Tomography ◽

Limited Stage ◽

Large B Cell Lymphoma ◽

Positron Emission ◽

Stage Disease ◽

Large B Cell

PURPOSE Diffuse large B-cell lymphoma (DLBCL) presents as a limited-stage disease in 25% to 30% of patients, with better overall survival (OS) than that for advanced-stage disease but with continuous relapse regardless of treatment approach. The preferred treatment is abbreviated rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and radiation therapy. On the basis of promising results of positron emission tomography (PET)–directed treatment approaches, we designed a National Clinical Trials Network (NCTN) study to improve outcomes and decrease toxicity. METHODS Patients with nonbulky (< 10 cm) stage I/II untreated DLBCL received 3 cycles of standard R-CHOP therapy and underwent a centrally reviewed interim PET/computed tomography scan (iPET). Those with a negative iPET proceeded with 1 additional cycle of R-CHOP, whereas those with a positive iPET received involved field radiation therapy followed by ibritumomab tiuxetan radioimmunotherapy. RESULTS Of 158 patients enrolled, 132 were eligible and 128 underwent iPET, which was positive in 14 (11%) of the patients. With a median follow-up of 4.92 years (range, 1.1-7.7 years), only 6 patients progressed and 3 died as a result of lymphoma. Eleven patients died as a result of nonlymphoma causes at a median age of 80 years. The 5-year progression-free survival estimate was 87% (95% CI, 79% to 92%) and the OS estimate was 89% (95% CI, 82% to 94%), with iPET-positive and iPET-negative patients having similar outcomes. CONCLUSION To our knowledge, S1001 is the largest prospective study in the United States of limited-stage DLBCL in the rituximab era, with the best NCTN results in this disease subset. With PET-directed therapy, 89% of the patients with a negative iPET received R-CHOP × 4, and only 11% had a positive iPET and required radiation, with both groups having excellent outcomes. The trial establishes R-CHOP × 4 alone as the new standard approach to limited-stage disease for the absolute majority of patients.

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Revisions to the International Neuroblastoma Response Criteria: A Consensus Statement From the National Cancer Institute Clinical Trials Planning Meeting

Journal of Clinical Oncology ◽

10.1200/jco.2016.72.0177 ◽

2017 ◽

Vol 35 (22) ◽

pp. 2580-2587 ◽

Cited By ~ 80

Author(s):

Julie R. Park ◽

Rochelle Bagatell ◽

Susan L. Cohn ◽

Andrew D. Pearson ◽

Judith G. Villablanca ◽

...

Keyword(s):

Positron Emission Tomography ◽

Bone Marrow ◽

Clinical Trials ◽

National Cancer Institute ◽

Emission Tomography ◽

Response Criteria ◽

Fluorodeoxyglucose Positron Emission Tomography ◽

Positron Emission ◽

Planning Meeting ◽

Fluorodeoxyglucose Positron Emission

Purpose More than two decades ago, an international working group established the International Neuroblastoma Response Criteria (INRC) to assess treatment response in children with neuroblastoma. However, this system requires modification to incorporate modern imaging techniques and new methods for quantifying bone marrow disease that were not previously widely available. The National Cancer Institute sponsored a clinical trials planning meeting in 2012 to update and refine response criteria for patients with neuroblastoma. Methods Multidisciplinary investigators from 13 countries reviewed data from published trials performed through cooperative groups, consortia, and single institutions. Data from both prospective and retrospective trials were used to refine the INRC. Monthly international conference calls were held from 2011 to 2015, and consensus was reached through review by working group leadership and the National Cancer Institute Clinical Trials Planning Meeting leadership council. Results Overall response in the revised INRC will integrate tumor response in the primary tumor, soft tissue and bone metastases, and bone marrow. Primary and metastatic soft tissue sites will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) and iodine-123 (123I) –metaiodobenzylguanidine (MIBG) scans or [18F]fluorodeoxyglucose–positron emission tomography scans if the tumor is MIBG nonavid. 123I-MIBG scans, or [18F]fluorodeoxyglucose–positron emission tomography scans for MIBG-nonavid disease, replace technetium-99m diphosphonate bone scintigraphy for osteomedullary metastasis assessment. Bone marrow will be assessed by histology or immunohistochemistry and cytology or immunocytology. Bone marrow with ≤ 5% tumor involvement will be classified as minimal disease. Urinary catecholamine levels will not be included in response assessment. Overall response will be defined as complete response, partial response, minor response, stable disease, or progressive disease. Conclusion These revised criteria will provide a uniform assessment of disease response, improve the interpretability of clinical trial results, and facilitate collaborative trial designs.

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Comparability of [18F]THK5317 and [11C]PIB blood flow proxy images with [18F]FDG positron emission tomography in Alzheimer’s disease

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16645593 ◽

2016 ◽

Vol 37 (2) ◽

pp. 740-749 ◽

Cited By ~ 24

Author(s):

Elena Rodriguez-Vieitez ◽

Antoine Leuzy ◽

Konstantinos Chiotis ◽

Laure Saint-Aubert ◽

Anders Wall ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Positron Emission Tomography ◽

Glucose Metabolism ◽

Early Phase ◽

Brain Perfusion ◽

Emission Tomography ◽

Discriminative Performance ◽

Positron Emission ◽

Alzheimer’S Disease Dementia

For amyloid positron emission tomography tracers, the simplified reference tissue model derived ratio of influx rate in target relative to reference region (R1) has been shown to serve as a marker of brain perfusion, and, due to the strong coupling between perfusion and metabolism, as a proxy for glucose metabolism. In the present study, 11 prodromal Alzheimer’s disease and nine Alzheimer’s disease dementia patients underwent [18F]THK5317, carbon-11 Pittsburgh Compound-B ([11C]PIB), and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography to assess the possible use of early-phase [18F]THK5317 and R1 as proxies for brain perfusion, and thus, for glucose metabolism. Discriminative performance (prodromal vs Alzheimer's disease dementia) of [18F]THK5317 (early-phase SUVr and R1) was compared with that of [11C]PIB (early-phase SUVr and R1) and [18F]FDG. Strong positive correlations were found between [18F]THK5317 (early-phase, R1) and [18F]FDG, particularly in frontal and temporoparietal regions. Differences in correlations between early-phase and R1 ([18F]THK5317 and [11C]PIB) and [18F]FDG, were not statistically significant, nor were differences in area under the curve values in the discriminative analysis. Our findings suggest that early-phase [18F]THK5317 and R1 provide information on brain perfusion, closely related to glucose metabolism. As such, a single positron emission tomography study with [18F]THK5317 may provide information about both tau pathology and brain perfusion in Alzheimer’s disease, with potential clinical applications.

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