Background
68
Ga-PSMA-11 positron emission tomography enables the detection of primary, recurrent, and metastatic prostate cancer. Regional radiopharmaceutical uptake is generally evaluated in static ...images and quantified as standard uptake values (SUVs) for clinical decision-making. However, analysis of dynamic images characterizing both tracer uptake and pharmacokinetics may offer added insights into the underlying tissue pathophysiology. This study was undertaken to evaluate the suitability of various kinetic models for
68
Ga-PSMA-11 PET analysis. Twenty-three lesions in 18 patients were included in a retrospective kinetic evaluation of 55-min dynamic
68
Ga-PSMA-11 pre-prostatectomy PET scans from patients with biopsy-demonstrated intermediate- to high-risk prostate cancer. Three kinetic models—a reversible one-tissue compartment model, an irreversible two-tissue compartment model, and a reversible two-tissue compartment model, were evaluated for their goodness of fit to lesion and normal reference prostate time-activity curves. Kinetic parameters obtained through graphical analysis and tracer kinetic modeling techniques were compared for reference prostate tissue and lesion regions of interest.
Results
Supported by goodness of fit and information loss criteria, the irreversible two-tissue compartment model optimally fit the time-activity curves. Lesions exhibited significant differences in kinetic rate constants (
K
1
,
k
2
,
k
3
,
K
i
) and semiquantitative measures (SUV and %ID/kg) when compared with reference prostatic tissue. The two-tissue irreversible tracer kinetic model was consistently appropriate across prostatic zones.
Conclusions
An irreversible tracer kinetic model is appropriate for dynamic analysis of
68
Ga-PSMA-11 PET images. Kinetic parameters estimated by Patlak graphical analysis or full compartmental analysis can distinguish tumor from normal prostate tissue.
Ga-PSMA-11 positron emission tomography enables the detection of primary, recurrent, and metastatic prostate cancer. Regional radiopharmaceutical uptake is generally evaluated in static images and ...quantified as standard uptake values (SUVs) for clinical decision-making. However, analysis of dynamic images characterizing both tracer uptake and pharmacokinetics may offer added insights into the underlying tissue pathophysiology. This study was undertaken to evaluate the suitability of various kinetic models for
Ga-PSMA-11 PET analysis. Twenty-three lesions in 18 patients were included in a retrospective kinetic evaluation of 55-min dynamic
Ga-PSMA-11 pre-prostatectomy PET scans from patients with biopsy-demonstrated intermediate- to high-risk prostate cancer. Three kinetic models-a reversible one-tissue compartment model, an irreversible two-tissue compartment model, and a reversible two-tissue compartment model, were evaluated for their goodness of fit to lesion and normal reference prostate time-activity curves. Kinetic parameters obtained through graphical analysis and tracer kinetic modeling techniques were compared for reference prostate tissue and lesion regions of interest.
Supported by goodness of fit and information loss criteria, the irreversible two-tissue compartment model optimally fit the time-activity curves. Lesions exhibited significant differences in kinetic rate constants (K
, k
, k
, K
) and semiquantitative measures (SUV and %ID/kg) when compared with reference prostatic tissue. The two-tissue irreversible tracer kinetic model was consistently appropriate across prostatic zones.
An irreversible tracer kinetic model is appropriate for dynamic analysis of
Ga-PSMA-11 PET images. Kinetic parameters estimated by Patlak graphical analysis or full compartmental analysis can distinguish tumor from normal prostate tissue.
Purpose
This study was undertaken to evaluate radiation dosimetry for the prostate-specific membrane antigen targeted
68
GaGa-P16-093 radiopharmaceutical, and to initially assess agent performance ...in positron emission tomography (PET) detection of the site of disease in prostate cancer patients presenting with biochemical recurrence.
Procedures
Under IND 133,222 and an IRB-approved research protocol, we evaluated the biodistribution and pharmacokinetics of
68
GaGa-P16-093 with serial PET imaging following intravenous administration to ten prostate cancer patients with biochemical recurrence. The recruited subjects were all patients in whom a recent
68
GaGa-PSMA-11 PET/X-ray computed tomography (CT) exam had been independently performed under IND 131,806 to assist in decision-making with regard to their clinical care. Voided urine was collected from each subject at ~ 60 min and ~ 140 min post-
68
GaGa-P16-093 injection and assayed for Ga-68 content. Following image segmentation to extract tissue time-activity curves and corresponding cumulated activity values, radiation dosimetry estimates were calculated using
IDAC Dose 2.1
. The prior
68
GaGa-PSMA-11 PET/CT exam (whole-body PET imaging at 60 min post-injection, performed with contrast-enhanced diagnostic CT) served as a reference scan for comparison to the
68
GaGa-P16-093 findings.
Results
68
GaGa-P16-093 PET images at 60 min post-injection provided diagnostic information that appeared equivalent to the subject’s prior
68
GaGa-PSMA-11 scan. With both radiopharmaceuticals, sites of tumor recurrence were found in eight of the ten patients, identifying 16 lesions. The site of recurrence was not detected with either agent for the other two subjects. Bladder activity was consistently lower with
68
GaGa-P16-093 than
68
GaGa-PSMA-11. The kidneys, spleen, salivary glands, and liver receive the highest radiation exposure from
68
GaGa-P16-093, with estimated doses of 1.7 × 10
−1
, 6.7 × 10
−2
, 6.5 × 10
−2
, and 5.6 × 10
−2
mGy/MBq, respectively. The corresponding effective dose from
68
GaGa-P16-093 is 2.3 × 10
−2
mSv/MBq.
Conclusions
68
GaGa-P16-093 provided diagnostic information that appeared equivalent to
68
GaGa-PSMA-11 in this limited series of ten prostate cancer patients presenting with biochemical recurrence, with the kidneys found to be the critical organ. Diminished tracer appearance in the urine represents a potential advantage of
68
GaGa-P16-093 over
68
GaGa-PSMA-11 for detection of lesions in the pelvis.
It is unclear if effects of glucagon-like peptide-1 (GLP-1) and clinically available GLP-1 agonists on the heart occur at clinical doses in humans, possibly contributing to reduced cardiovascular ...disease risk.
To determine whether liraglutide, at clinical dosing, augments myocardial glucose uptake (MGU) alone or combined with insulin compared with insulin alone in metformin-treated type 2 diabetes mellitus (T2D).
In a randomized clinical trial of patients with T2D treated with metformin plus oral agents or basal insulin, myocardial fuel use was compared after 3 months of treatment with insulin detemir, liraglutide, or combination detemir plus liraglutide added to background metformin.
Myocardial blood flow (MBF), fuel selection, and rates of fuel use were evaluated using positron emission tomography, powered to demonstrate large effects.
MBF was greater in the insulin-treated groups median (25th, 75th percentile): detemir, 0.64 mL/g/min (0.50, 0.69); liraglutide, 0.52 mL/g/min (0.46, 0.58); detemir plus liraglutide, 0.75 mL/g/min (0.55, 0.77); P = 0.035 comparing three groups, P = 0.01 comparing detemir groups to liraglutide alone. There were no evident differences among groups in MGU detemir, 0.040 µmol/g/min (0.013, 0.049); liraglutide, 0.055 µmol/g/min (0.019, 0.105); detemir plus liraglutide, 0.037 µmol/g/min (0.009, 0.046); P = 0.68 comparing three groups. There were no treatment-group differences in measures of myocardial fatty acid uptake or handling, and no differences in total oxidation rate.
These observations argue against large effects of GLP-1 agonists on myocardial fuel metabolism as mediators of beneficial treatment effects on myocardial function and ischemia protection.
Introduction: This study was performed to estimate the human radiation dosimetry for 68GaGa-HBED-CC (PSMA-11) (68Ga PSMA-11). Methods: Under an RDRC-approved research protocol, we evaluated the ...biodistribution and pharmacokinetics of 68Ga PSMA-11 with serial PET imaging following intravenous administration to nine prostate cancer patients in whom clinical 11Cacetate PET/CT exams had been independently performed under Expanded Access IND 118,204. List-mode imaging was performed over the initial 0-10 min post-injection with the pelvis in the field-of-view. Whole-body images were acquired, pelvis-to-head, at 15, 60, and 90-min post-injection. Additional images of the pelvis were acquired at 40-min and 115-min, and voided urine collected from each subject at 48-min and 120-min post-injection. Radiation dosimetry estimates were calculated from these data using the OLINDA software package. Results: Renal uptake was high and relatively invariant, ranging from 11% to 14% of the injected dose between 15 and 90-min post-injection. Radioactivity collected in the voided urine accounted for 14% of the injected dose over a period of 120-min. Lymph nodes and skeletal metastases suspicious for prostate cancer recurrence were detected in a greater number of patients using 68Ga PSMA-11 than using 11C-acetate. Conclusion: Kidneys are the critical organ following 68Ga PSMA-11 administration, receiving an estimated dose of 0.413 mGy/MBq. Advances in knowledge and implications for patient care: This study confirms that the kidneys will be the critical organ following intravenous administration of 68Ga PSMA-11, and provided data consistent with the expectation that 68Ga PSMA-11 will be superior to 11Cacetate for defining sites of recurrence in prostate cancer patients presenting with biochemical relapse.
Abstract Introduction: This study was performed to estimate the human radiation dosimetry for 68 GaGa-HBED-CC (PSMA-11) (68 Ga PSMA-11). Methods: Under an RDRC-approved research protocol, we ...evaluated the biodistribution and pharmacokinetics of68 Ga PSMA-11 with serial PET imaging following intravenous administration to nine prostate cancer patients in whom clinical 11 Cacetate PET/CT exams had been independently performed under Expanded Access IND 118,204. List-mode imaging was performed over the initial 0–10 min post-injection with the pelvis in the field-of-view. Whole-body images were acquired, pelvis-to-head, at 15, 60, and 90-min post-injection. Additional images of the pelvis were acquired at 40-min and 115-min, and voided urine collected from each subject at 48-min and 120-min post-injection. Radiation dosimetry estimates were calculated from these data using the OLINDA software package. Results: Renal uptake was high and relatively invariant, ranging from 11% to 14% of the injected dose between 15 and 90-min post-injection. Radioactivity collected in the voided urine accounted for 14% of the injected dose over a period of 120-min. Lymph nodes and skeletal metastases suspicious for prostate cancer recurrence were detected in a greater number of patients using68 Ga PSMA-11 than using11 C–acetate. Conclusion: Kidneys are the critical organ following68 Ga PSMA-11 administration, receiving an estimated dose of 0.413 mGy/MBq. Advances in Knowledge and Implications for Patient Care: This study confirms that the kidneys will be the critical organ following intravenous administration of68 Ga PSMA-11, and provided data consistent with the expectation that68 Ga PSMA-11 will be superior to 11 Cacetate for defining sites of recurrence in prostate cancer patients presenting with biochemical relapse.
This study was performed to estimate the human radiation dosimetry for 68GaGa-HBED-CC (PSMA-11) (68Ga PSMA-11).
Under an RDRC-approved research protocol, we evaluated the biodistribution and ...pharmacokinetics of 68Ga PSMA-11 with serial PET imaging following intravenous administration to nine prostate cancer patients in whom clinical 11Cacetate PET/CT exams had been independently performed under Expanded Access IND 118,204. List-mode imaging was performed over the initial 0–10min post-injection with the pelvis in the field-of-view. Whole-body images were acquired, pelvis-to-head, at 15, 60, and 90-min post-injection. Additional images of the pelvis were acquired at 40-min and 115-min, and voided urine collected from each subject at 48-min and 120-min post-injection. Radiation dosimetry estimates were calculated from these data using the OLINDA software package.
Renal uptake was high and relatively invariant, ranging from 11% to 14% of the injected dose between 15 and 90-min post-injection. Radioactivity collected in the voided urine accounted for 14% of the injected dose over a period of 120-min. Lymph nodes and skeletal metastases suspicious for prostate cancer recurrence were detected in a greater number of patients using 68Ga PSMA-11 than using 11C-acetate.
Kidneys are the critical organ following 68Ga PSMA-11 administration, receiving an estimated dose of 0.413mGy/MBq.
This study confirms that the kidneys will be the critical organ following intravenous administration of 68Ga PSMA-11, and provided data consistent with the expectation that 68Ga PSMA-11 will be superior to 11Cacetate for defining sites of recurrence in prostate cancer patients presenting with biochemical relapse.
This study was performed to estimate the human radiation dosimetry for
GaGa-HBED-CC (PSMA-11) (
Ga PSMA-11).
Under an RDRC-approved research protocol, we evaluated the biodistribution and ...pharmacokinetics of
Ga PSMA-11 with serial PET imaging following intravenous administration to nine prostate cancer patients in whom clinical
Cacetate PET/CT exams had been independently performed under Expanded Access IND 118,204. List-mode imaging was performed over the initial 0-10min post-injection with the pelvis in the field-of-view. Whole-body images were acquired, pelvis-to-head, at 15, 60, and 90-min post-injection. Additional images of the pelvis were acquired at 40-min and 115-min, and voided urine collected from each subject at 48-min and 120-min post-injection. Radiation dosimetry estimates were calculated from these data using the OLINDA software package.
Renal uptake was high and relatively invariant, ranging from 11% to 14% of the injected dose between 15 and 90-min post-injection. Radioactivity collected in the voided urine accounted for 14% of the injected dose over a period of 120-min. Lymph nodes and skeletal metastases suspicious for prostate cancer recurrence were detected in a greater number of patients using
Ga PSMA-11 than using
C-acetate.
Kidneys are the critical organ following
Ga PSMA-11 administration, receiving an estimated dose of 0.413mGy/MBq.
This study confirms that the kidneys will be the critical organ following intravenous administration of
Ga PSMA-11, and provided data consistent with the expectation that
Ga PSMA-11 will be superior to
Cacetate for defining sites of recurrence in prostate cancer patients presenting with biochemical relapse.
Retinal vein occlusion is the second most common retinal vascular disease. Bevacizumab was demonstrated in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) to be noninferior ...to aflibercept with respect to visual acuity in study participants with macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) following 6 months of therapy. In this study, the cost-utility of bevacizumab vs aflibercept for treatment of CRVO is evaluated.
To investigate the relative cost-effectiveness of bevacizumab vs aflibercept for treatment of macular edema associated with CRVO or HRVO.
This economic evaluation study used a microsimulation cohort of patients with clinical and demographic characteristics similar to those of SCORE2 participants and a Markov process. Parameters were estimated and validated using a split-sample approach of the SCORE2 population. The simulated cohort included 5000 patients who were evaluated 100 times, each with a different set of characteristics randomly selected based on the SCORE2 trial. SCORE2 data were collected from September 2014 October 2019, and data were analyzed from October 2019 to July 2021.
Bevacizumab (followed by aflibercept among patients with a protocol-defined poor or marginal response to bevacizumab at month 6) vs aflibercept (followed by a dexamethasone implant among patients with a protocol-defined poor or marginal response to aflibercept at month 6).
Incremental cost-utility ratio.
The simulation demonstrated that patients treated with aflibercept will have an expected cost $18 127 greater than those treated with bevacizumab in the year following initiation. When coupled with the lack of clinical superiority over bevacizumab (ie, patients treated with bevacizumab had a gain over aflibercept in visual acuity letter score of 4 in the treated eye and 2 in the fellow eye), these results demonstrate that first-line treatment with bevacizumab dominated aflibercept in the simulated cohort of SCORE2 participants. At current price levels, aflibercept would be considered the preferred cost-effective option only if treatment restored the patient to nearly perfect health.
While there will be some patients with CRVO-associated or HRVO-associated macular edema who will benefit from first-line treatment with aflibercept rather than bevacizumab, given the minimal differences in visual acuity outcomes and large cost differences for bevacizumab vs aflibercept, first-line treatment with bevacizumab is cost-effective for this condition.
![[68Ga]Ga-P16-093 as a PSMA-...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1536-1632_1860-2002/small "[68Ga]Ga-P16-093 as a PSMA-Targeted PET Radiopharmaceutical for Detection of Cancer: Initial Evaluation and Comparison with [68Ga]Ga-PSMA-11 in Prostate Cancer Patients Presenting with Biochemical Recurrence")
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