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PurposeNon-invasive imaging is a key clinical tool for detection and treatment monitoring of infections. Existing clinical imaging techniques are frequently unable to distinguish infection from tumors or sterile inflammation. This challenge is well-illustrated by prosthetic joint infections that often complicate joint replacements. D-methyl-11C-methionine (D-11C-Met) is a new bacteria-specific PET radiotracer, based on an amino acid D-enantiomer, that is rapidly incorporated into the bacterial cell wall. In this manuscript, we describe the biodistribution, radiation dosimetry, and initial human experience using D-11C-Met in patients with suspected prosthetic joint infections.Methods614.5 ± 100.2 MBq of D-11C-Met was synthesized using an automated in-loop radiosynthesis method and administered to six healthy volunteers and five patients with suspected prosthetic joint infection, who were studied by PET/MRI. Time-activity curves were used to calculate residence times for each source organ. Absorbed doses to each organ and body effective doses were calculated using OLINDA/EXM 1.1 with both ICRP 60 and ICRP 103 tissue weighting factors. SUVmax and SUVpeak were calculated for volumes of interest (VOIs) in joints with suspected infection, the unaffected contralateral joint, blood pool, and soft tissue background. A two-tissue compartment model was used for kinetic modeling.ResultsD-11C-Met was well tolerated in all subjects. The tracer showed clearance from both urinary (rapid) and hepatobiliary (slow) pathways as well as low effective doses. Moreover, minimal background was observed in both organs with resident micro-flora and target organs, such as the spine and musculoskeletal system. Additionally, D-11C-Met showed increased focal uptake in areas of suspected infection, demonstrated by a significantly higher SUVmax and SUVpeak calculated from VOIs of joints with suspected infections compared to the contralateral joints, blood pool, and background (P

A major obstacle to achieving long-term antiretroviral (ART) free remission or functional cure of HIV infection is the presence of persistently infected cells that establish a long-lived viral reservoir. HIV largely resides in anatomical regions that are inaccessible to routine sampling, however, and non-invasive methods to understand the longitudinal tissue-wide burden of HIV persistence are urgently needed. Positron emission tomography (PET) imaging is a promising strategy to identify and characterize the tissue-wide burden of HIV. Here, we assess the efficacy of using immunoPET imaging to characterize HIV reservoirs and identify anatomical foci of persistent viral transcriptional activity using a radiolabeled HIV Env-specific broadly neutralizing antibody, 89Zr-VRC01, in HIV-infected individuals with detectable viremia and on suppressive ART compared to uninfected controls (NCT03729752). We also assess the relationship between PET tracer uptake in tissues and timing of ART initiation and direct HIV protein expression in CD4 T cells obtained from lymph node biopsies. We observe significant increases in 89Zr-VRC01 uptake in various tissues (including lymph nodes and gut) in HIV-infected individuals with detectable viremia (N = 5) and on suppressive ART (N = 5) compared to uninfected controls (N = 5). Importantly, PET tracer uptake in inguinal lymph nodes in viremic and ART-suppressed participants significantly and positively correlates with HIV protein expression measured directly in tissue. Our strategy may allow non-invasive longitudinal characterization of residual HIV infection and lays the framework for the development of immunoPET imaging in a variety of other infectious diseases.

BackgroundAmino acid PET imaging of brain tumors has been shown to play an important role in predicting tumor grade, delineation of tumor margins, and differentiating tumor recurrence from the background of postradiation changes, but is not commonly used in clinical practice because of high cost. We propose that PET/MRI imaging of patients grouped to the day of tracer radiosynthesis will significantly decrease the cost of PET imaging, which will improve patient access to PET.MethodsSeventeen patients with either primary brain tumors or metastatic brain tumors were recruited for imaging on 3T PET/MRI and were scanned on 4 separate days in groups of 3 to 5 patients. The first group of consecutively imaged patients contained 3 patients, followed by 2 groups of 5 patients, and a last group of 4 patients.ResultsFor each of the patients, standard of care gadolinium-enhanced MRI and dynamic PET imaging with 18F-FDOPA amino acid tracer was obtained. The total cost savings of scanning 17 patients in batches of 4 as opposed to individual radiosynthesis was 48.5% ($28 321). Semiquantitative analysis of tracer uptake in normal brain were performed with appropriate accumulation and expected subsequent washout.ConclusionAmino acid PET tracers have been shown to play a critical role in the characterization of brain tumors but their adaptation to clinical practice has been limited because of the high cost of PET. Scheduling patient imaging to maximally use the radiosynthesis of imaging tracer significantly reduces the cost of PET and results in increased availability of PET tracer use in neuro-oncology.

A major obstacle to achieving long-term antiretroviral (ART) free remission or functional cure of HIV infection is the presence of persistently infected cells that establish a long-lived viral reservoir. HIV largely resides in anatomical regions that are inaccessible to routine sampling, however, and non-invasive methods to understand the longitudinal tissue-wide burden of HIV persistence are urgently needed. Positron emission tomography (PET) imaging is a promising strategy to identify and characterize the tissue-wide burden of HIV. Here, we assess the efficacy of using immunoPET imaging to characterize HIV reservoirs and identify anatomical foci of persistent viral transcriptional activity using a radiolabeled HIV Env-specific broadly neutralizing antibody, 89Zr-VRC01, in HIV-infected individuals with detectable viremia and on suppressive ART compared to uninfected controls (NCT03729752). We also assess the relationship between PET tracer uptake in tissues and timing of ART initiation and direct HIV protein expression in CD4 T cells obtained from lymph node biopsies. We observe significant increases in 89Zr-VRC01 uptake in various tissues (including lymph nodes and gut) in HIV-infected individuals with detectable viremia (N = 5) and on suppressive ART (N = 5) compared to uninfected controls (N = 5). Importantly, PET tracer uptake in inguinal lymph nodes in viremic and ART-suppressed participants significantly and positively correlates with HIV protein expression measured directly in tissue. Our strategy may allow non-invasive longitudinal characterization of residual HIV infection and lays the framework for the development of immunoPET imaging in a variety of other infectious diseases. Here, the authors apply positron emission tomography (PET) imaging to visualize HIV tissue-wide burden in infected individuals using a radiolabeled broadly neutralizing antibody, 89Zr-VRC01, and show that PET tracer lymph node uptake positively correlates with HIV protein levels measured directly from cells obtained from these tissues. This strategy may allow non-invasive characterization of residual HIV infection in the setting of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Purpose: Non-invasive imaging is a key clinical tool for detection and treatment monitoring of infections. Existing clinical imaging techniques are frequently unable to distinguish infection from tumors or sterile inflammation. This challenge is well-illustrated by prosthetic joint infections that often complicate joint replacements. D-methyl-11C-methionine (D-11C-Met) is a new bacteria-specific PET radiotracer, based on an amino acid D-enantiomer, that is rapidly incorporated into the bacterial cell wall. In this manuscript, we describe the biodistribution, radiation dosimetry, and initial human experience using D-11C-Met in patients with suspected prosthetic joint infections. Methods: 614.5 ± 100.2 MBq of D-11C-Met was synthesized using an automated in-loop radiosynthesis method and administered to six healthy volunteers and five patients with suspected prosthetic joint infection, who were studied by PET/MRI. Time-activity curves were used to calculate residence times for each source organ. Absorbed doses to each organ and body effective doses were calculated using OLINDA/EXM 1.1 with both ICRP 60 and ICRP 103 tissue weighting factors. SUVmax and SUVpeak were calculated for volumes of interest (VOIs) in joints with suspected infection, the unaffected contralateral joint, blood pool, and soft tissue background. A two-tissue compartment model was used for kinetic modeling. Results: D-11C-Met was well tolerated in all subjects. The tracer showed clearance from both urinary (rapid) and hepatobiliary (slow) pathways as well as low effective doses. Moreover, minimal background was observed in both organs with resident micro-flora and target organs, such as the spine and musculoskeletal system. Additionally, D-11C-Met showed increased focal uptake in areas of suspected infection, demonstrated by a significantly higher SUVmax and SUVpeak calculated from VOIs of joints with suspected infections compared to the contralateral joints, blood pool, and background (P < 0.01). Furthermore, higher distribution volume and binding potential were observed in suspected infections compared to the unaffected joints. Conclusion: D-11C-Met has a favorable radiation profile, minimal background uptake, and fast urinary extraction. Furthermore, D-11C-Met showed increased uptake in areas of suspected infection, making this a promising approach. Validation in larger clinical trials with a rigorous gold standard is still required. [ABSTRACT FROM AUTHOR]

Background Amino acid PET imaging of brain tumors has been shown to play an important role in predicting tumor grade, delineation of tumor margins, and differentiating tumor recurrence from the background of postradiation changes, but is not commonly used in clinical practice because of high cost. We propose that PET/MRI imaging of patients grouped to the day of tracer radiosynthesis will significantly decrease the cost of PET imaging, which will improve patient access to PET. Methods Seventeen patients with either primary brain tumors or metastatic brain tumors were recruited for imaging on 3T PET/MRI and were scanned on 4 separate days in groups of 3 to 5 patients. The first group of consecutively imaged patients contained 3 patients, followed by 2 groups of 5 patients, and a last group of 4 patients. Results For each of the patients, standard of care gadolinium-enhanced MRI and dynamic PET imaging with 18F-FDOPA amino acid tracer was obtained. The total cost savings of scanning 17 patients in batches of 4 as opposed to individual radiosynthesis was 48.5% ($28 321). Semiquantitative analysis of tracer uptake in normal brain were performed with appropriate accumulation and expected subsequent washout. Conclusion Amino acid PET tracers have been shown to play a critical role in the characterization of brain tumors but their adaptation to clinical practice has been limited because of the high cost of PET. Scheduling patient imaging to maximally use the radiosynthesis of imaging tracer significantly reduces the cost of PET and results in increased availability of PET tracer use in neuro-oncology. [ABSTRACT FROM AUTHOR]

Purpose: Non-invasive imaging is a key clinical tool for detection and treatment monitoring of infections. Existing clinical imaging techniques are frequently unable to distinguish infection from tumors or sterile inflammation. This challenge is well-illustrated by prosthetic joint infections that often complicate joint replacements. D-methyl- 11 C-methionine (D- 11 C-Met) is a new bacteria-specific PET radiotracer, based on an amino acid D-enantiomer, that is rapidly incorporated into the bacterial cell wall. In this manuscript, we describe the biodistribution, radiation dosimetry, and initial human experience using D- 11 C-Met in patients with suspected prosthetic joint infections., Methods: 614.5 ± 100.2 MBq of D- 11 C-Met was synthesized using an automated in-loop radiosynthesis method and administered to six healthy volunteers and five patients with suspected prosthetic joint infection, who were studied by PET/MRI. Time-activity curves were used to calculate residence times for each source organ. Absorbed doses to each organ and body effective doses were calculated using OLINDA/EXM 1.1 with both ICRP 60 and ICRP 103 tissue weighting factors. SUV max and SUV peak were calculated for volumes of interest (VOIs) in joints with suspected infection, the unaffected contralateral joint, blood pool, and soft tissue background. A two-tissue compartment model was used for kinetic modeling., Results: D- 11 C-Met was well tolerated in all subjects. The tracer showed clearance from both urinary (rapid) and hepatobiliary (slow) pathways as well as low effective doses. Moreover, minimal background was observed in both organs with resident micro-flora and target organs, such as the spine and musculoskeletal system. Additionally, D- 11 C-Met showed increased focal uptake in areas of suspected infection, demonstrated by a significantly higher SUV max and SUV peak calculated from VOIs of joints with suspected infections compared to the contralateral joints, blood pool, and background (P < 0.01). Furthermore, higher distribution volume and binding potential were observed in suspected infections compared to the unaffected joints., Conclusion: D- 11 C-Met has a favorable radiation profile, minimal background uptake, and fast urinary extraction. Furthermore, D- 11 C-Met showed increased uptake in areas of suspected infection, making this a promising approach. Validation in larger clinical trials with a rigorous gold standard is still required., (© 2022. The Author(s).)

A major obstacle to achieving long-term antiretroviral (ART) free remission or functional cure of HIV infection is the presence of persistently infected cells that establish a long-lived viral reservoir. HIV largely resides in anatomical regions that are inaccessible to routine sampling, however, and non-invasive methods to understand the longitudinal tissue-wide burden of HIV persistence are urgently needed. Positron emission tomography (PET) imaging is a promising strategy to identify and characterize the tissue-wide burden of HIV. Here, we assess the efficacy of using immunoPET imaging to characterize HIV reservoirs and identify anatomical foci of persistent viral transcriptional activity using a radiolabeled HIV Env-specific broadly neutralizing antibody, 89 Zr-VRC01, in HIV-infected individuals with detectable viremia and on suppressive ART compared to uninfected controls (NCT03729752). We also assess the relationship between PET tracer uptake in tissues and timing of ART initiation and direct HIV protein expression in CD4 T cells obtained from lymph node biopsies. We observe significant increases in 89 Zr-VRC01 uptake in various tissues (including lymph nodes and gut) in HIV-infected individuals with detectable viremia (N = 5) and on suppressive ART (N = 5) compared to uninfected controls (N = 5). Importantly, PET tracer uptake in inguinal lymph nodes in viremic and ART-suppressed participants significantly and positively correlates with HIV protein expression measured directly in tissue. Our strategy may allow non-invasive longitudinal characterization of residual HIV infection and lays the framework for the development of immunoPET imaging in a variety of other infectious diseases., (© 2022. The Author(s).)

Background: Amino acid PET imaging of brain tumors has been shown to play an important role in predicting tumor grade, delineation of tumor margins, and differentiating tumor recurrence from the background of postradiation changes, but is not commonly used in clinical practice because of high cost. We propose that PET/MRI imaging of patients grouped to the day of tracer radiosynthesis will significantly decrease the cost of PET imaging, which will improve patient access to PET., Methods: Seventeen patients with either primary brain tumors or metastatic brain tumors were recruited for imaging on 3T PET/MRI and were scanned on 4 separate days in groups of 3 to 5 patients. The first group of consecutively imaged patients contained 3 patients, followed by 2 groups of 5 patients, and a last group of 4 patients., Results: For each of the patients, standard of care gadolinium-enhanced MRI and dynamic PET imaging with 18 F-FDOPA amino acid tracer was obtained. The total cost savings of scanning 17 patients in batches of 4 as opposed to individual radiosynthesis was 48.5% ($28 321). Semiquantitative analysis of tracer uptake in normal brain were performed with appropriate accumulation and expected subsequent washout., Conclusion: Amino acid PET tracers have been shown to play a critical role in the characterization of brain tumors but their adaptation to clinical practice has been limited because of the high cost of PET. Scheduling patient imaging to maximally use the radiosynthesis of imaging tracer significantly reduces the cost of PET and results in increased availability of PET tracer use in neuro-oncology., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)