Paolo Gerundini

Biodistribution of Tc-99m methoxy-isobutyl-isonitrile (MIBI) in humans

Hexakis (methoxyisobutilisonitrile) technetium(I), 99mTc-MIBI, has been proposed for myocardial perfusion studies. We have evaluated the biodistribution of this new agent in normal volunteers at rest and after stress. The biodistribution of 99mTc-MIBI is characterized by rapid blood clearance and a consequently early myocardial uptake. The initial intense hepatic activity is cleared into the gallbladder at 1 h after injection, and the best target to non target ratio is observed at 60–90 min after injection. Absorbed radiation dose calculations show that the thyroid is the critical target organ (230 mRad/mCi at rest), presumably because of 99mTc-pertechnetate generated in vivo. Our results indicate that 99mTc-MIBI is a promising tracer for myocardial perfusion imaging.

Remote Effects of Subcortical Cerebrovascular Lesions: A SPECT Cerebral Perfusion Study

The remote effects of small unilateral cerebrovascular lesions confined to subcortical structures were evaluated by single photon emission computerized tomography (SPECT) and a CBF tracer, I-123 HIPDM. A CBF study was performed in 34 patients presenting with subcortical stroke either in the acute or in the chronic stages. Twenty-one of the 34 patients showed areas of cortical hypoperfusion ipsilateral to the subcortical lesion. In 14 patients, asymmetry of perfusion was also observed at the cerebellar level, perfusion being significantly reduced in the cerebellar hemisphere contralateral to the lesion. There was no correlation between the degree and extension of these remote effects and the type of stroke (ischemic or hemorrhagic), the patency of cerebral arteries, or the size and site of the lesion by transmissive computerized tomography (TCT). Subcortical hematomas showed a correlation between occurrence of remote effects and time interval from the onset of stroke, occurring more frequently in the acute phase. A correlation was observed between cortical and cerebellar remote effects and the severity of clinical presentation. The causes of remote effects are still unclear and have been extensively debated. Our data indicate that there is a relationship of remote effect to the neurological status. It is possible to show, by noninvasive, low-cost methods, remote CBF effects after stroke that may contribute to the assessment of brain functional impairment.

Striatal dopamine transporter abnormalities in patients with essential tremor

Background and methodsWe used 123I-Ioflupane SPECT to study 32 unrelated patients with essential tremor (16 with positive familial history), 47 sporadic tremor dominant patients with Parkinsons disease and 31 healthy control subjects. Discriminant analysis was used to categorize healthy subjects and patients with Parkinsons disease or essential tremor. ResultsPatients with essential tremor had higher uptake values (50% putamen and 21% caudate, P<0.001) compared to those with Parkinsons disease but lower than healthy subjects (15% putamen and 21% caudate, P<0.05). Discriminant analysis classified seven essential tremor patients in the healthy subjects cohort (22%) and two as Parkinsons disease (6%). ConclusionsOur results show that some essential tremor patients may present mild abnormalities of striatal dopamine transporters and a typical Parkinsons disease-like pattern of uptake loss. These findings suggest a link between the two disorders.

Abnormal cardiovascular response to exercise in young asymptomatic diabetic patients with retinopathy

Heart rate, blood pressure, and left ventricular ejection fraction (LVEF) were measured by means of Au 195 m first-pass angiocardiography, during maximal supine bicycle exercise in 20 young asymptomatic patients with insulin-dependent diabetes (IDD) (10 retinopathic and 10 uncomplicated) and in 10 control subjects. Five patients with retinopathic IDD also had mild subclinical autonomic neuropathy. Exercise capacity was diminished, although not significantly, in patients with retinopathic IDD. Heart rate and LVEF were similar in all groups at rest and at submaximal exercise. At peak exercise patients with retinopathic IDD had significantly lower heart rate (134 +/- 4 bpm) and LVEF (62.9 +/- 3.7%) than those with umcomplicated IDD (158 +/- 8 bpm and 76.6 +/- 2.4%, respectively) and control subjects (152 +/- 6 bpm and 73.5 +/- 1.9%, respectively). LVEF increased vs baseline in all control subjects and patients with uncomplicated IDD, but in only three with retinopathic IDD. Leg muscle blood flow (MBF) was also evaluated at rest and during exercise by 133Xe washout. Exercise MBF was significantly lower in patients with retinopathic IDD (40.5 +/- 2.23 ml X min-1 X 100 gm-1) than in control subjects (49.9 +/- 1.87 ml X min-1 X 100 gm-1) and in those with uncomplicated IDD (49.0 +/- 1.87 ml X min-1 X 100 gm-1). Diffuse microangiopathy, alone or in combination with neuropathy, might be responsible for the impairment of cardiovascular function in diabetes.

[123I]FP-CIT striatal binding in early Parkinson's disease patients with tremor vs. akinetic-rigid onset.

We performed [123I]FP-CIT/SPECT in 20 drug-naive Parkinsons disease (PD) patients, 10 with unilateral akinesia/rigidity at onset (arPD) and 10 with additional tremor-at-rest (tPD), to evaluate whether resting tremor at onset is associated with differences in striatal dopamine transporter binding. Patients of the two cohorts were matched for age, disease duration (<3 years) and severity of nontremor motor symptoms; 31 healthy participants served as controls. Mean striatal dopamine transporter binding reduction in PD patients vs. controls was 42% for arPD and 50% for tPD; mean ipsilateral striatum and caudate nucleus uptake values were lower by 12 and 24%, respectively, in tPD than arPD. We conclude that widespread degeneration of the nigrostriatal dopaminergic pathway might be necessary for the development of parkinsonian tremor-at-rest.

Angioplasty of atherosclerotic and fibromuscular renal artery stenosis: Time course and predicting factors of the effects on renal function

The effects of percutaneous transluminal renal angioplasty (PTRA) on the renal function of stenotic kidneys are usually assessed by evaluating the changes in serum creatinine, which is quite a rough indicator of glomerular filtration rate (GFR). In 27 hypertensive patients with 19 atherosclerotic and 11 fibromuscular significant renal artery stenoses, we investigated with renal scintigraphy the short-term (5 days) and long-term (10 months) effects of a technically successful PTRA (in seven cases combined with a stent implantation) on GFR of the stenotic and contralateral kidneys; these measurements were combined with those of plasma renin activity (PRA) and of angiotensin II (AII). We found that in short-term studies after PTRA GFR rose from 29.7 +/- 3.5 to 34.6 +/- 3.1 mL/min and from 36.9 +/- 4.0 to 45.1 +/- 4.3 mL/min, respectively, in atherosclerotic and fibromuscular poststenotic kidneys. In long-term studies GFR further and significantly increased, to 37.8 +/- 3.2 mL/min in the former group, whereas it stabilized in the latter group (46.0 +/- 3.6 mL/min). In patients with fibromuscular stenosis these changes in GFR were associated with clear-cut reductions in blood pressure (BP), PRA, and AII; these decrements also occurred in patients with atherosclerotic stenosis but to a much lesser extent. We also found that in short- and long-term studies the percent of PTRA-induced increments of GFR in the poststenotic kidneys were inversely correlated with the baseline values of GFR. In addition, the absolute and percent increments of GFR were positively correlated with the basal levels of AII. Thus the time course of the improvement in GFR after angioplasty may differ in kidneys, depending on the etiology of the stenosis, in that in those with fibromuscular stenosis it was entirely apparent within a few days whereas in those with atherosclerotic stenosis it required several months to be fully expressed. Also, it appears that the more compromised kidneys are those that benefit most from the dilatation and that AII levels are useful indicators of the possibility that the stenotic kidney will have a favorable functional outcome in terms of restoration of renal blood flow.

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.

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.

Role of Tc-99m sestamibi scintigraphy in the diagnosis and surgical decision-making process in primary hyperparathyroid disease

Purpose Ultrasound (US) and scintigraphy are used most frequently of all the available imaging techniques for the preoperative evaluation of patients with possible primary hyperparathyroid disease. The aim of this study was to assess the value of dual-phase Tc-99m MIBI scintigraphy compared with US in the detection of adenomatous or hyperplastic glands and in the surgical decision-making process for patients with a biochemical diagnosis of primary hyperparathyroid disease. Methods Ninety-seven patients with increased levels of parathyroid hormone and calcium, and at least 6 months’ follow-up after US and scintigraphy, were examined retrospectively to assess the influence of the diagnostic work-up on the therapeutic decision of the referring clinicians and to evaluate the sensitivity of these diagnostic tools in the surgically treated patients. Forty-eight patients underwent surgery. Results Parathyroid adenomas were found in 43 patients and hyperplasia in 1, whereas 4 patients had no evidence at surgery. The sensitivity and specificity rates were 84.4% and 95.9% for scintigraphy, and 66.6% and 98.6% for US, respectively. Of the 49 nonsurgically treated patients, 35 had negative results with both MIBI and US; only 3 had positive findings with both imaging methods. Patients treated conservatively had significantly lower parathyroid hormone and serum calcium levels than did the patients who had surgery. Conclusions The data suggest that the high sensitivity of dual-phase MIBI scintigraphy can improve the detection of hyperfunctioning parathyroid glands. Furthermore, despite the controversy surrounding the use of imaging methods in the preoperative assessment of primary hyperparathyroid disease, these data suggest that the decision of the clinician to order surgery for a patient with a moderate increase of serum PTH level may be influenced by the results of the imaging methods.

Striatal dopamine transporter binding in Parkinson's disease associated with the LRRK2 Gly2019Ser mutation

We measured striatal dopamine transporter binding using [123I]ioflupane and SPECT in patients with Parkinsons disease associated with the LRRK2 (PARK8) Gly2019Ser gene mutation (LRRK2‐PD) and in gene‐negative patients with idiopathic Parkinsons disease (IPD) of comparable disease duration and severity. The LRRK2‐PD group consisted of a total of 10 patients (3 sporadic) with mean age 62 ± 14 years, disease duration 9 ± 3 years, and UPDRS III motor score 21.60 ± 6.65. The control IPD group consisted of 15 patients with mean age 59 ± 9 years, disease duration 9 ± 5 years, and UPDRS III motor score 23.80 ± 8.69. [123I]ioflupane–specific uptake ratios were calculated for caudate nucleus and putamen using the occipital cortex as reference region. We found no differences between the LRRK2‐PD group and IPD in all items studied. In particular, putamen and caudate uptake values as well as side asymmetry indexes and putamen/caudate ratios all revealed comparable between‐group values. We conclude that in these patients carrying the LRRK2 Gly2019Ser mutation, the neurodegenerative process results in a pattern of nigrostriatal dopaminergic dysfunction similar to that observed in IPD.