Article

Radiation dosimetry and biodistribution of the TSPO ligand 11C-DPA-713 in humans.

Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Journal of Nuclear Medicine (Impact Factor: 5.56). 02/2012; 53(2):330-5. DOI: 10.2967/jnumed.111.094565
Source: PubMed

ABSTRACT Whole-body PET/CT was used to characterize the radiation dosimetry of (11)C-DPA-713, a specific PET ligand for the assessment of translocator protein.
Six healthy control subjects, 3 men and 3 women, underwent whole-body dynamic PET scans after bolus injection of (11)C-DPA-713. Subjects were scanned from head to mid thigh with 7 passes performed, with a total PET acquisition of approximately 100 min. Time-activity curves were generated in organs with visible tracer uptake, and tissue residence times were calculated. Whole-body dosimetry was calculated using OLINDA 1.1 software, assuming no voiding.
The absorbed dose is highest in the lungs, spleen, kidney, and pancreas. The lungs were determined to be the dose-limiting organ, with an average absorbed dose of 2.01 × 10(-2) mSv/MBq (7.43 × 10(-2) rem/mCi). On the basis of exposure limits outlined in the U.S. Food and Drug Administration Code of Federal Regulations (21CFR361.1), the single-dose limit for (11)C-DPA-713 radiotracer injection is 2,487.6 MBq (67.3 mCi).
(11)C-DPA-713 has an uptake pattern that is consistent with the biodistribution of translocator protein and yields a dose burden that is comparable to that of other (11)C-labeled PET tracers.

0 Bookmarks
 · 
132 Views
  • Biomarkers in Medicine 06/2014; 8(5):605-7. · 3.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Early diagnosis of and subsequent monitoring of therapy for rheumatoid arthritis (RA) could benefit from detection of (sub)clinical synovitis. Imaging of (sub)clinical arthritis by targeting the translocator protein (TSPO) on activated macrophages is feasible using (R)-[11C] PK11195-based positron emission tomography (PET), but clinical applications are limited by background uptake in peri-articular bone/bone marrow. The purpose of the present study was to evaluate two other TSPO ligands with potentially lower background uptake in neurological studies, [11C]DPA-713 and [18F]DPA-714, in a rat model of arthritis. TSPO binding of DPA-713, DPA-714 and PK11195 were assessed by in vitro competition studies with [3H]DPA-713 using human macrophage THP-1 cells and CD14+ monocytes from healthy volunteers. In vivo studies were performed in rats with methylated bovine serum albumin-induced knee arthritis. Immunohistochemistry with anti-TSPO antibody was performed on paraffin-embedded sections. Rats were imaged with [11C]DPA-713 or [18F]DPA-714 PET, followed by ex vivo tissue distribution studies. Results were compared with the tracer (R)-[11C]PK11195, the established ligand for TSPO. In THP-1 cells, relative TSPO binding of DPA-713 and DPA-714 were 7-fold and 25-fold higher, respectively, than in PK11195. Comparable results were observed in CD14+ monocytes from healthy volunteers. In the arthritis rat model, immunohistochemistry confirmed the presence of TSPO-positive inflammatory cells in the arthritic knee. PET images showed that uptake of [11C]DPA-713 and [18F]DPA-714 in arthritic knees was significantly increased compared with contralateral knees and knees of normal rats. Uptake in arthritic knees could be largely blocked by an excess of PK11195. [11C]DPA-713 and [18F]DPA-714 provided improved contrast compared with (R)-[11C]PK11195, as was shown by significantly higher arthritic knee-to-bone ratios of [11C]DPA-713 (1.60 +/- 0.31) and [18F]DPA-714 (1.55 +/- 0.10) compared with (R)-[11C]PK11195 (1.14 +/- 0.19). [11C]DPA-713 and [18F]DPA-714 clearly visualized arthritis and exhibited lower (peri-articular) bone/bone marrow uptake than (R)-[11C]PK11195. These features merit further investigation of these tracers for early diagnosis and therapy monitoring of RA in a clinical setting.
    Arthritis research & therapy 03/2014; 16(2):R70. · 4.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Imaging the brain distribution of translocator protein (TSPO), a putative biomarker for glial cell activation and neuroinflammation, may inform management of individuals infected with HIV by uncovering regional abnormalities related to neurocognitive deficits and enable non-invasive therapeutic monitoring. Using the second-generation TSPO-targeted radiotracer, [(11)C]DPA-713, we conducted a positron emission tomography (PET) study to compare the brains of 12 healthy human subjects to those of 23 individuals with HIV who were effectively treated with combination antiretroviral therapy (cART). Compared to PET data from age-matched healthy control subjects, [(11)C]DPA-713 PET of individuals infected with HIV demonstrated significantly higher volume-of-distribution (VT) ratios in white matter, cingulate cortex, and supramarginal gyrus, relative to overall gray matter VT, suggesting localized glial cell activation in susceptible regions. Regional TSPO abnormalities were evident within a sub-cohort of neuro-asymptomatic HIV subjects, and an increase in the VT ratio within frontal cortex was specifically linked to individuals affected with HIV-associated dementia. These findings were enabled by employing a gray matter normalization approach for PET data quantification, which improved test-retest reproducibility, intra-class correlation within the healthy control cohort, and sensitivity of uncovering abnormal regional findings.
    Journal of NeuroVirology 02/2014; · 2.85 Impact Factor

Full-text

Download
52 Downloads
Available from
May 20, 2014