Robert K. Doot
VerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 2003–2026
Research topics
- Oncology
- Medicine
- Medical physics
- Pharmacology
- Nuclear medicine
- Internal medicine
Selected publications
arXiv (Cornell University) · 2026-03-31
preprintOpen accessBackground: Renal blood flow (RBF) is an important marker of kidney health, but noninvasive assessment is not routinely used in clinical imaging. We evaluated the feasibility and physiologic validity of quantifying renal transport of Rubidium-82 (K1) during standard myocardial perfusion imaging (MPI) PET. Methods: We studied 126 patients (age 60 +/- 12 years; 48% male; 51% Black) undergoing clinically indicated rest and stress Rb-82 MPI, in whom at least one kidney was partially visualized within the axial field of view. Volumes of interest were drawn over the visible renal cortex. K1 was estimated using a one-tissue compartment model with arterial input functions (AIF) derived from either the left ventricle (LV) or abdominal aorta. Results: LV-derived AIF produced physiologic and internally consistent flow estimates, whereas aorta-derived AIF systematically overestimated K1 and flow. LV-based measurements were therefore used for all analyses. K1 demonstrated nonlinear flow dependence consistent with the Renkin-Crone extraction model, plateauing at higher perfusion states. Renal K1 and flow declined progressively with worsening kidney function, from 1.24 +/- 0.35 ml/min/g (eGFR >= 60) to 0.53 +/- 0.22 ml/min/g (eGFR < 15; P < 0.0001). Only patients with preserved eGFR showed significant hyperemic augmentation. ROC analysis demonstrated excellent discrimination for reduced kidney function (AUC > 0.90). Conclusion: Opportunistic renal K1 quantification during routine Rb-82 PET is feasible, physiologically consistent, and strongly associated with kidney function.
Psychiatry Research Neuroimaging · 2026-01-29 · 1 citations
articleOpen accessAcute alcohol use reduces brain glucose metabolism while increasing uptake of acetate, a byproduct of alcohol. This metabolic shift persists in individuals with alcohol use disorder (AUD) and may offer a treatment target. Recent studies show that ketone therapies can lessen alcohol withdrawal and cravings. In this study, we tested whether a single dose of a ketone ester (KE) supplement affects brain energy use and alcohol craving. Ten participants (five with AUD, five healthy controls) received two FDG-PET brain scans-one after taking 395 mg/kg KE and one at baseline-in a randomized order. Additionally, five AUD participants underwent magnetic resonance spectroscopy to measure cingulate β-hydroxybutyrate (BHB). KE lowered blood glucose and increased BHB in both groups. Brain scans revealed a 17% reduction in glucose metabolism, especially in the frontal, occipital, and cingulate cortices, as well as the hippocampus, amygdala, and insula. No major differences were observed between AUD and control groups. KE significantly reduced alcohol craving in AUD participants and tripled cingulate BHB levels. These findings suggest that a single KE dose can rapidly shift brain energy use from glucose to ketones, and may help reduce cravings in AUD, supporting its potential as a therapeutic approach.
arXiv (Cornell University) · 2026-03-31
articleOpen accessBackground: Renal blood flow (RBF) is an important marker of kidney health, but noninvasive assessment is not routinely used in clinical imaging. We evaluated the feasibility and physiologic validity of quantifying renal transport of Rubidium-82 (K1) during standard myocardial perfusion imaging (MPI) PET. Methods: We studied 126 patients (age 60 +/- 12 years; 48% male; 51% Black) undergoing clinically indicated rest and stress Rb-82 MPI, in whom at least one kidney was partially visualized within the axial field of view. Volumes of interest were drawn over the visible renal cortex. K1 was estimated using a one-tissue compartment model with arterial input functions (AIF) derived from either the left ventricle (LV) or abdominal aorta. Results: LV-derived AIF produced physiologic and internally consistent flow estimates, whereas aorta-derived AIF systematically overestimated K1 and flow. LV-based measurements were therefore used for all analyses. K1 demonstrated nonlinear flow dependence consistent with the Renkin-Crone extraction model, plateauing at higher perfusion states. Renal K1 and flow declined progressively with worsening kidney function, from 1.24 +/- 0.35 ml/min/g (eGFR >= 60) to 0.53 +/- 0.22 ml/min/g (eGFR < 15; P < 0.0001). Only patients with preserved eGFR showed significant hyperemic augmentation. ROC analysis demonstrated excellent discrimination for reduced kidney function (AUC > 0.90). Conclusion: Opportunistic renal K1 quantification during routine Rb-82 PET is feasible, physiologically consistent, and strongly associated with kidney function.
2025-11-25
articleOpen access<p>Baseline [18F]FTT imaging correlates.</p>
Mendeley Data · 2025-12-25
datasetOpen accessHuntington's disease is a neurodegenerative condition resulting from an expanded CAG repeat in the huntingtin gene that produces a mutant form of the huntingtin protein (mHTT). In this study we estimated the radiation safety of two structurally related mHTT radioligands, [18F]CHDI-385 and [18F]CHDI-386, by evaluating the in vivo and ex vivo dosimetry of both radioligands using CD-1 Swiss mice. We used adult male and female CD-1 Swiss mice (n = 15 per sex/radioligand) to assess in vivo positron emission tomography/computed tomography (PET/CT) imaging-based and ex vivo biodistribution-based tracer distribution of the radioligands at 30-, 60-, 120-, 240-, and 360-minutes post-radioligand injection. Organ activity was quantified, and the residence time was extrapolated to human phantoms. The absorbed and effective doses were estimated using OLINDA/EXM 2.2 and IDAC-Dose2.1. Both radioligands, [18F]CHDI-385 and [18F]CHDI-386, showed high uptake in the gallbladder and urinary bladder, with a slow washout in most organs. The colon wall received the highest equivalent organ dose for both modalities. Ex vivo effective dose estimates were 15.4 μSv/MBq for [18F]CHDI-385 and 16.3 μSv/MBq for [18F]CHDI-386, while in vivo effective dose estimates were 18.5 μSv/MBq and 18.7 μSv/MBq, respectively. [18F]CHDI-385 and [18F]CHDI-386 dosimetry results showed absorbed and effective doses in acceptable range and below the recommended limits. An injection of 370 MBq (10 mCi) in humans is estimated to result in highest (in vivo) effective doses of 6.85 mSv for [18F]CHDI-385 and 6.92 mSv for [18F]CHDI-386. This datasets has both in vivo and ex vivo data shared for [18F]CHDI-386.
Mendeley Data · 2025-12-25
datasetOpen accessHuntington's disease is a neurodegenerative condition resulting from an expanded CAG repeat in the huntingtin gene that produces a mutant form of the huntingtin protein (mHTT). In this study we estimated the radiation safety of two structurally related mHTT radioligands, [18F]CHDI-385 and [18F]CHDI-386, by evaluating the in vivo and ex vivo dosimetry of both radioligands using CD-1 Swiss mice. We used adult male and female CD-1 Swiss mice (n = 15 per sex/radioligand) to assess in vivo positron emission tomography/computed tomography (PET/CT) imaging-based and ex vivo biodistribution-based tracer distribution of the radioligands at 30-, 60-, 120-, 240-, and 360-minutes post-radioligand injection. Organ activity was quantified, and the residence time was extrapolated to human phantoms. The absorbed and effective doses were estimated using OLINDA/EXM 2.2 and IDAC-Dose2.1. Both radioligands, [18F]CHDI-385 and [18F]CHDI-386, showed high uptake in the gallbladder and urinary bladder, with a slow washout in most organs. The colon wall received the highest equivalent organ dose for both modalities. Ex vivo effective dose estimates were 15.4 μSv/MBq for [18F]CHDI-385 and 16.3 μSv/MBq for [18F]CHDI-386, while in vivo effective dose estimates were 18.5 μSv/MBq and 18.7 μSv/MBq, respectively. [18F]CHDI-385 and [18F]CHDI-386 dosimetry results showed absorbed and effective doses in acceptable range and below the recommended limits. An injection of 370 MBq (10 mCi) in humans is estimated to result in highest (in vivo) effective doses of 6.85 mSv for [18F]CHDI-385 and 6.92 mSv for [18F]CHDI-386. This datasets has both in vivo and ex vivo data shared for [18F]CHDI-386.
2025-11-25
articleOpen access<p>18F]FTT-PET on subject previously treated with PARPi.</p>
Journal of Nuclear Medicine · 2025-11-13 · 1 citations
articleOpen accessF]CHDI-385 is a radioligand with optimal properties for detecting and quantifying cerebral mHTT aggregates and support its clinical evaluation.
2025-11-25
articleOpen access<p>Clinical response correlates.</p>
European Journal of Nuclear Medicine and Molecular Imaging · 2025-06-17 · 4 citations
article
Recent grants
Methodology for PET Imaging of Role of Dopamine D3 Receptor in Addiction
NIH · $809k · 2016–2021
Frequent coauthors
- 139 shared
David A. Mankoff
University of Pennsylvania
- 80 shared
Erin K. Schubert
- 62 shared
Lisa K. Dunnwald
- 62 shared
Julie R. Gralow
- 60 shared
Jennifer M. Specht
Fred Hutch Cancer Center
- 60 shared
Hannah M. Linden
University of Washington
- 59 shared
Brenda F. Kurland
University of Washington Medical Center
- 56 shared
Robert H. Mach
University of Pennsylvania
Education
- 2008
Ph.D., Bioengineering (and Nanotechnology)
University of Washington
- 2005
M.S., Bioengineering
University of Washington
- 1992
B.S., Chemical Engineering
University of Michigan
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