Cristina Canzi

Myocardial blood flow and infarct size after CD133+ cell injection in large myocardial infarction with good recanalization and poor reperfusion: Results from a randomized controlled trial

Objective Large acute ST-elevation myocardial infarction (STEMI) sometimes leaves extensive ischemic damage despite timely and successful primary angioplasty. This clinical picture of good recanalization with incomplete reperfusion represents a good model to assess the reparative potential of locally administered cell therapy. Thus, we conducted a randomized controlled trial aimed at evaluating the effect of intracoronary administration of CD133+ stem cells on myocardial blood flow and function in this setting. Methods Fifteen patients with large anterior STEMI, myocardial blush grade 0–1 and more than 50% ST-elevation recovery after optimal coronary recanalization (TIMI 3 flow) with stenting were randomly assigned to receive CD133+ cells from either bone marrow (group A) or peripheral blood (group B), or to stay on drug therapy alone (group C). The cells were intracoronary injected within 10–14 days of STEMI. Infarct-related myocardial blood flow (MBF) was evaluated by NH3 positron emission tomography 2–5 days before cell administration and after 1 year. Results MBF increased in the infarct area from 0.419 (0.390–0.623) to 0.544 (0.371–0.729) ml/min per g in group A, decreased from 0.547 (0.505–0.683) to 0.295 (0.237–0.472) ml/min per g in group B and only slightly changed from 0.554 (0.413–0.662) to 0.491 (0.453–0.717) ml/min per g in group C (A vs. C: P = 0.023; B vs. C: P = 0.066). Left ventricular volume tended to increase more in groups B and C than in group A, ejection fraction and wall motion score index remained stable in the three groups. Conclusion These findings support the hypothesis that intracoronary administration of bone marrow-derived, but not peripheral blood-derived CD133+ cells 10–14 days after STEMI may improve long-term perfusion.

EANM Dosimetry Committee Series on Standard Operational Procedures for Pre-Therapeutic Dosimetry II. Dosimetry prior to radioiodine therapy of benign thyroid diseases

The EANM Dosimetry Committee Series “Standard Operational Procedures for Pre-Therapeutic Dosimetry” (SOP) provides advice to scientists and clinicians on how to perform patient-specific absorbed dose assessments. This particular SOP describes how to tailor the therapeutic activity to be administered for radioiodine therapy of benign thyroid diseases such as Graves’ disease or hyperthyroidism. Pretherapeutic dosimetry is based on the assessment of the individual 131I kinetics in the target tissue after the administration of a tracer activity. The present SOP makes proposals on the equipment to be used and guides the user through the measurements. Time schedules for the measurement of the fractional 131I uptake in the diseased tissue are recommended and it is shown how to calculate from these datasets the therapeutic activity necessary to administer a predefined target dose in the subsequent therapy. Potential sources of error are pointed out and the inherent uncertainties of the procedures depending on the number of measurements are discussed. The theoretical background and the derivation of the listed equations from compartment models of the iodine kinetics are explained in a supplementary file published online only.

The Role of PET with 13N-Ammonia and 18F-FDG in the Assessment of Myocardial Perfusion and Metabolism in Patients with Recent AMI and Intracoronary Stem Cell Injection

Over the last decade, the effects of stem cell therapy on cardiac repair after acute myocardial infarction (AMI) have been investigated with different imaging techniques. We evaluated a new imaging approach using 13N-ammonia and 18F-FDG PET for a combined analysis of cardiac perfusion, metabolism, and function in patients treated with intracoronary injection of endothelial progenitors or with conventional therapy for AMI. Methods: A total of 15 patients were randomly assigned to 3 groups based on different treatments (group A: bone marrow–derived stem cells; group B: peripheral blood–derived stem cells; group C: standard therapy alone). The number of scarred and viable segments, along with the infarct size and the extent of the viable area, were determined on a 9-segment 13N-ammonia/18F-FDG PET polar map. Myocardial blood flow (MBF) was calculated for each segment on the ammonia polar map, whereas a global evaluation of left ventricular function was obtained by estimating left ventricular ejection fraction (LVEF) and end-diastolic volume, both derived from electrocardiography-gated 18F-FDG images. Both intragroup and intergroup comparative analyses of the mean values of each parameter were performed at baseline and 3, 6, and 12 mo after AMI. During follow-up, major cardiac events were also registered. Results: A significant decrease (P < 0.05) in the number of scarred segments and infarct size was observed in group A, along with an increase in MBF (P < 0.05) and a mild improvement in cardiac function. Lack of infarct size shrinkage in group B was associated with a marked impairment of MBF (P = 0.01) and cardiac dysfunction. Ambiguous changes in infarct size, MBF, and LVEF were found in group C. No differences in number of viable segments or in extent of viable area were found among the groups. At clinical follow-up, no major cardiac events occurred in group A patients, whereas 2 patients of group B experienced in-stent occlusion and one patient of group C received a transplant for heart failure. Conclusion: Our data suggest that a single nuclear imaging technique accurately analyzes changes in myocardial perfusion and metabolism occurring after stem cell transplantation.

Tissue-specific dosimetry for radioiodine therapy of the autonomous thyroid nodule

A tissue-specific dosimetric method based on gamma camera acquisitions was developed to determine the 131I activity to administer to patients with autonomous thyroid nodules (ATN) to deliver 200 Gy to the nodule and to evaluate the correspondent dose to extranodular tissue. Twenty patients with ATN were given 111 MBq of 123I i.v. and their neck was imaged 2, 4, 24, 48, and 120 hours after administration to evaluate separate iodine kinetics for nodule and contralateral lobe. The volumes of nodule and lobe were measured on the 4 hour scintigraphic image, after optimization of the method on a thyroid phantom. Three simplified dosimetric methods were then considered and compared to the reference method in terms of 131I activity: (a) three point method, based on 4, 24, and 120 h acquisitions, (b) fixed T1/2 method, that measures only the 24 h uptake and assumes an effective half-life of 5 days for the nodule, (c) fixed activity method, based on the administration of 413 MBq of 131I. The mean 131I activity to administer to the 20 patients was 413 MBq (range 65-1327) and the mean dose to the contralateral lobe was 43 Gy (range 11-121). The percentage differences in 131I activity between the reference method and the simplified methods were in the ranges: (a) -14%, 13%, (b) -42%, 74%, (c) -69%, 533%. The relevant dose to extranodular tissue and the great interpatient variability of the radioiodine activity required to give a predetermined dose to ATN suggest that a tissue specific dosimetric approach based on gamma camera acquisitions is fundamental. A simple method based on only three uptake measurements is a reliable alternative to the five point method when the clinical workload of a Nuclear Medicine department is particularly heavy.

Potential third-party radiation exposure from outpatients treated with 131I for hyperthyroidism.

Thirty-three hyperthyroid patients treated with radioiodine (mean administered activity 414 MBq, range 163-555) were studied to determine if pretreatment dosimetry could be used to give radiation protection advice that could assure compliance with the effective dose constraints suggested by the European Commission. Effective doses to travelers, co-workers, and sleeping partners were estimated by integrating the effective dose rate-versus-time curve obtained by fitting the dose rates measured several times after radioiodine administration to a biexponential function. The mean estimated effective doses to travelers, co-workers, and sleeping partners were 0.11 mSv (0.05-0.24), 0.24 mSv (0.07-0.52), and 1.8 mSv (0.6-4.1), respectively. The best correlation was found between effective dose (D) in mSv and maximum activity (AUmax) in MBq taken up in the thyroid: Dtraveler=0.0005 * (AUmax) +0.04 (r=0.88,p< 0.01); Dco-worker=0.0013 * (A Umax) +0.03 (r=0.89,p < 0.01); Dsleeping partners=0.0105 * (AUmax)+0.16 (r=0.93,p < 0.01). Private/public transports are always allowed. For the co-workers the effective dose constraint of 0.3 mSv is met without restrictions and with 3 days off work if AUmax is lower or higher than 185 MBq, respectively. For the sleeping partners the effective dose constraint of 3 mSv is met without restriction and with 4 nights separate sleeping arrangements if AUmax is lower or higher than 185 MBq, respectively. The potential for contamination by the patients was determined from perspiration samples taken from the patients hands, forehead, and neck and in saliva at 4, 24, and 48 h after radioiodine treatment. The mean highest 131I activity levels for hands, forehead, neck, and saliva were 4.1 Bq/cm2, 1.9 Bq/cm2, 0.9 Bq/cm2, and 796 kBq/g, respectively. The results indicate that there is minimal risk of contamination from these patients.

Changes in the energy response of a dedicated gamma camera after exposure to a high-flux irradiation

This work reports the effects of the gain variation of the photomultiplier tubes (PMTs) observed on a cardiac dedicated gamma camera after accidental high-flux irradiation. One detector of this dual-headed 90 degrees-fixed gamma camera was accidentally left uncollimated during a quality assurance procedure on the other detector with a 57Co flood source (259 MBq) and received a non-uniform high flux of 1.9-0.6 Mcps over 25000 mm2 areas for about 30 min. To evaluate the severity and the duration of the perturbation effect on the energy response of the detector, the photopeak position was monitored for about 1 month with a 99mTc point source. The 140 keV photopeak shifted to 158 keV soon after irradiation, reached the correct position after 9 days and moved to a stable value of 132 keV after 15 days. Afterwards, a new energy calibration reset the photopeak position at 140 keV and the correct energy response of the gamma camera. This experience suggests that particular care should be taken to avoid exposures to high radiation fluxes that induce persistent gain shifts on the PMTs of this system.

Dosimetry in the Radioiodine Treatment of Hyperthyroidism

Radioiodine therapy has largely replaced surgery and is nowadays commonly used because it is easy to perform and has proved to be effective in the definitive treatment of hyperthyroidism.