Orit Jacobson

Localization of parathyroid adenoma by ¹¹C-choline PET/CT: preliminary results.

Purpose This prospective pilot study was aimed to evaluate 11C-choline PET/CT (choline) as a tool for localization of parathyroid adenoma (PTA). Methods Forty patients with biochemical hyperparathyroidism underwent choline and 99mTc-MIBI imaging within a median interval of 56 days. Choline and MIBI images were analyzed and correlated with each other, with additional modalities such as ultrasound, CT, MRI, and with surgical findings, when available. Results Thirty-seven of forty cases were choline-positive, and 3 were choline-negative. Choline uptake on PET was identified with corresponding nodules on CT of the PET/CT, yielding precise localization. Twenty of thirty-seven foci were located in typical sites in the neck, and 17 were ectopic. Clear visualization of PTA was achieved in 33 of 37, whereas findings in 4 cases were suspicious for PTA. MIBI was positive in 33 of 40 cases (22 clearly positive, 11 suspicious). In 29 of 40 cases, choline and MIBI were concordant, but choline findings were clearer in 9 of these 29 studies. At the time of writing, 27 patients had undergone surgery. In 24 cases, there was complete matching of choline with surgical findings of PTA. Overall in 23 cases, both choline and MIBI matched surgical findings of PTA. In 1 case, PTA was correctly localized on choline but not on MIBI, and in 2 cases, neither choline nor MIBI corresponded to the surgical findings. Conclusions These preliminary results indicate that the combined functional and anatomical modality of choline PET/CT is a promising tool for PTA localization, providing clearer images than MIBI, equal or better accuracy, and quicker and easier acquisition.

Rat Imaging and In Vivo Stability Studies using [11C]-Dimethyl-Diphenyl Ammonium, a Candidate Agent for PET-Myocardial Perfusion Imaging

BACKGROUND PET myocardial perfusion imaging (MPI) holds several advantages over SPECT for diagnosing coronary artery disease. The short half-lives of prevailing PET-MPI agents hamper wider clinical application of PET in nuclear cardiology; prompting the development of novel PET-MPI agents. We have previously reported on the potential of radiolabeled ammonium salts, and particularly on that of [(11)C]dimethyl-diphenyl-ammonium ([(11)C]DMDPA), for cardiac PET imaging. This study was designed to improve the radiosynthesis and increase the yield of [(11)C]DMDPA, characterize more meticulously the kinetics of radioactivity distribution after its injection via micro-PET/CT studies, and further explore its potential for PET-MPI. METHODS The radiosynthetic procedure of [(11)C]DMDPA was improved with respect to the previously reported one. The kinetics of radioactivity distribution following injection of [(11)C]DMDPA were investigated in juvenile and young adult male SD rats using microPET/CT, and compared to those of [(13)N]NH3. Furthermore, the metabolic fate of [(11)C]DMDPA in vivo was examined after its injection into rats. RESULTS Following a radiosynthesis time of 25-27 min, 11.9 ± 1.1 GBq of [(11)C]DMDPA was obtained, with a 43.7% ± 4.3% radiochemical yield (n = 7). Time activity curves calculated after administration of [(11)C]DMDPA indicated rapid, high and sustained radioactivity uptake in hearts of both juvenile and young adult rats, having a two-fold higher cardiac radioactivity uptake compared to [(13)N]NH3. Accordingly, at all time points after injection to both juvenile and young adult rats, image quality of the left ventricle was higher with [(11)C]DMDPA compared to [(13)N]NH3. In vivo stability studies of [(11)C]DMDPA indicate that no radioactive metabolites could be detected in plasma, liver and urine samples of rats up to 20 min after injection, suggesting that [(11)C]DMDPA is metabolically stable in vivo. CONCLUSIONS This study further illustrates that [(11)C]DMDPA holds, at least in part, essential qualities required from a PET-MPI probe. Owing to the improved radiosynthetic procedure reported herein, [(11)C]DMDPA can be produced in sufficient amounts for clinical use.

PET molecular imaging of angiogenesis with a multiple tyrosine kinase receptor-targeted agent in a rat model of myocardial infarction.

PurposeAngiogenesis plays a major role in tissue remodeling and repair after myocardial infarction (MI), and imaging it could provide information on the healing process. During angiogenesis, vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs), and Tie receptors are upregulated, and this study aimed to develop a C-11 positron emission tomography (PET) agent for imaging angiogenesis by targeting these receptors.ProceduresA VEGFR-2/Tie-2/PDGFRα inhibitor (N-(6-{4-[3-(2-fluoro-5-trifluoromethyl-phenyl)-ureido]-phenoxy}-1H-benzoimidazol-2-yl)-2-(4-methyl-piperazin-1-yl)-acetamide (ATV-1)) was synthesized and labeled with C-11. MicroPET imaging of a rat MI model was compared to proteins expression by immunohistochemistry.Results[11C]ATV-1 specifically accumulated in the infracted region of the left ventricular (LV) lateral wall more than in the interventricular septal wall, but not in sham-operated or healthy animals. Moreover, [11C]ATV-1 uptake in the LV significantly correlated with Tie-2, VEGFR-2, and PDGFRα expression.ConclusionImaging angiogenesis in MI rats using [11C]ATV-1 and PET has been demonstrated. These results merit further research and development of more hydrophilic modified [11C]ATV-1 as a PET tracer.