Georg Riccabona

Impaired dopaminergic neurotransmission in patients with traumatic brain injury: a SPET study using 123I-β-CIT and 123I-IBZM

Abstract. Structural imaging suggests that traumatic brain injury (TBI) may be associated with disruption of neuronal networks, including the nigrostriatal dopaminergic pathway. However, to date deficits in pre- and/or postsynaptic dopaminergic neurotransmission have not been demonstrated in TBI using functional imaging. We therefore assessed dopaminergic function in ten TBI patients using [123I]2-β-carbomethoxy-3-β-(4-iodophenyl)tropane (β-CIT) and [123I]iodobenzamide (IBZM) single-photon emission tomography (SPET). Average Glasgow Coma Scale score (±SD) at the time of head trauma was 5.8±4.2. SPET was performed on average 141 days (SD ±92) after TBI. The SPET images were compared with structural images using cranial computerised tomography (CCT) and magnetic resonance imaging (MRI). SPET was performed with an ADAC Vertex dual-head camera. The activity ratios of striatal to cerebellar uptake were used as a semiquantitative parameter of striatal dopamine transporter (DAT) and D2 receptor (D2R) binding. Compared with age-matched controls, patients with TBI had significantly lower striatal/cerebellar β-CIT and IBZM binding ratios (P≤0.01). Overall, the DAT deficit was more marked than the D2R loss. CCT and MRI studies revealed varying cortical and subcortical lesions, with the frontal lobe being most frequently affected whereas the striatum appeared structurally normal in all but one patient. Our findings suggest that nigrostriatal dysfunction may be detected using SPET following TBI despite relative structural preservation of the striatum. Further investigations of possible clinical correlates and efficacy of dopaminergic therapy in patients with TBI seem justified.

Thallium-201 gated single-photon emission tomography for the assessment of left ventricular ejection fraction and regional wall motion abnormalities in comparison with two-dimensional echocardiography

Abstract. Simultaneous assessment of myocardial perfusion and function by gated single-photon emission tomography (GS) after a single tracer injection provides incremental information and is feasible with technetium-99m sestamibi. The present study validated the use of GS with thallium-201 for the assessment of left ventricular ejection fraction (LVEF) and regional wall motion by comparison with two-dimensional (2D) echocardiography (echo), which has not been done before. After injection of 111 MBq 201Tl at peak bicycle exercise (n=55) or pharmacological stress (n=17), GS was acquired 15 (post stress) and 120 min post injection (rest) on a double-head camera. An automatic algorithm (QGS) was used for processing. Echo (Acuson Sequoia C256) was performed immediately after rest GS. LVEFs assessed by GS and echo were correlated. The overall and segmental sensitivity and specificity of GS for the detection of regional wall motion abnormalities (WMAs) were calculated, echo serving as the gold standard. Perfusion abnormalities were scored. The success rate of the automatic algorithm was 100%, and visually assessed image quality was good to excellent in 88% of cases. Post-stress and rest LVEF as assessed by GS were highly correlated (r=0.91). Good correlations were obtained between post-stress LVEF (GS) and rest LVEF (echo) and between rest LVEF (GS) and rest LVEF (echo) (r=0.76 and 0.86 respectively). In patients with a reduced LVEF of less than 50% (n=23), these correlations were even better (r=0.84 and 0.89 respectively). Regional wall motion abnormalities (WMAs) were identified by GS with high sensitivity and specificity (88%–100% and 82%–98% respectively) and were directly related to the extent and severity of stress as well as of resting perfusion defects. It is concluded that GS with 201Tl is a feasible and reliable tool for the evaluation of patients with compromised left ventricular function in the context of coronary artery disease, and thus improves diagnosis and prognostic stratification. Regional WMAs were identified with high diagnostic accuracy and the method may prove helpful for the detection of myocardial viability.

123I-β-CIT and 123I-IBZM-SPECT scanning in levodopa-naive Parkinson's disease

Striatal dopamine transporter function and dopamine D2 receptor status were evaluated in 15 patients with early untreated Parkinsons disease using single photon emission tomography (SPECT) with 123I‐Iodo‐2β‐carboxymethoxy‐3β‐(4‐idiophenyl)tropane (β‐CIT) and 123I‐Iodobenzamide (IBZM) as pre‐ and postsynaptic ligands. Symptoms were unilateral in five patients and bilateral but asymmetric in 10 patients. Patients with bilateral symptoms had significantly lower 18‐hour striatal/cerebellar β‐CIT binding ratios (3.59 ± 0.79) than hemiparkinsonian patients (5.76 ± 1.48, p < 0.05) reflecting more advanced disease in this subgroup. Patients with bilateral parkinsonism were also found to have a significant side‐to‐side difference in striatal β‐CIT binding with more marked reduction contralateral to the presenting limb (18‐hour striatal/cerebellar ratio: 4.13 ± 0.78 [ipsilateral] versus 3.59 ± 0.79 [contralateral], p < 0.05). Dopamine D2 receptor binding as measured by IBZM was significantly elevated contralateral to the affected side in hemiparkinsonian patients (striatal/cerebellar ratio: 2.42 ± 0.90 [contralateral] versus 2.19 ± 0.80 [ipsilateral], p < 0.05). This asymmetric upregulation was absent in the patients with bilateral parkinsonism (striatal/cerebellar ratio: 1.85 ± 0.43 [contralateral to more severely affected side] versus 1.83 ± 0.34 [ipsilateral], p > 0.05). Our data suggest that postsynaptic dopamine receptor upregulation contralateral to the presenting side occurs in untreated unilateral PD and disappears in untreated bilateral (asymmetric) PD despite a greater loss of dopamine transporter function. Combined β‐CIT and IBZM SPECT studies may be helpful to monitor the progression of nigrostriatal dysfunction in early PD.

Evaluation of Striatal Dopamine Transporter Function in Rats by in Vivo β-[123I]CIT Pinhole SPECT

Striatal dopamine transporter (DAT) function was evaluated in rats by in vivo SPECT-MRI coregistration using the radioligand 2-beta-carbomethoxy-3-beta-(4-[123I]iodophenyl)tropane (beta-[123I]CIT). The reconstructed transaxial resolution of 3.5 mm full width at half-maximum and the system sensitivity of 0.081 c/s/kBq using a 2.0-mm pinhole collimator aperture provided adequate spatial detail and sufficient sensitivity for imaging striatal beta-[123I]CIT uptake. SPECT images, coregistered onto a MRI template, showed high accuracy in the coronal and transverse planes (maximum mismatch of 1.3 mm). Following estimation of the in vivo binding equilibrium of beta-[123I]CIT in the healthy rat striatum, we evaluated the 6-hydroxydopamine-induced loss of striatal DAT function using beta-[123I]CIT SPECT and MRI coregistration and correlated these findings with dopaminergic cell counts in the substantia nigra pars compacta using TH immunohistochemistry. A subtotal unilateral DAT deficit was detected by beta-[123I]CIT SPECT in all animals which correlated significantly with the cell counting of the remaining dopaminergic neurons. beta-[123I]CIT pinhole SPECT provides a powerful and widely available tool for in vivo investigations of rat striatal DAT function. In contrast to classical autoradiography, the present method will be helpful in imaging dynamic changes of neurotransmission in the CNS by virtue of serial study designs. Depending on SPECT ligand availability, a wide range of other CNS receptors may be imaged as well using the presented in vivo technique.

Peptide targeted imaging of cancer.

After the discovery of several specific peptide receptors in a variety of cancer types more than 10 years ago, radiolabeled peptide analogs with adequate stability, receptor binding properties, and biokinetic behavior were introduced for imaging of neuroendocrine tumors, several adenocarcinomas, lymphoma, and melanoma. Although initially 123I or 111In were used for labeling, recent efforts have also concentrated on 99mTc or PET-radionuclides (18F,68Ga), as they result in better image resolution with lower radiation dose to patients. Scintigraphy with labeled somatostatin analogs (99mTc, 111In,18F,68Ga), with 123I-labeled vasoactive intestinal peptide, and recently 99mTc-bombesin/GRP-or-111In gastrin analogs, have shown a mean sensitivity of greater than 85% to localize deposits of tumors, with appropriate receptor expression frequently scarcely visible with other imaging procedures. Moreover, these observations introduced peptide-targeted metabolic radiotherapy for metastatic cancers. This development has produced a considerable amount of preclinical studies to broaden the impact of labeled peptide ligands on the management of cancer.

Management of Hyperparathyroidism in an Endemic Goiter Area

Abstract. In an endemic goiter area patients with hyperparathyroidism (HPTH) frequently also have thyroid abnormalities. In a retrospective study of 95 patients with HPTH we assessed the diagnostic accuracy of imaging techniques (ultrasonography or radionuclide scanning) for preoperative localization of parathyroid adenomas. Altogether 86% of our patients had goiter, requiring thyroid resections in 37%. For 19 patients the parathyroid exploration was the second or third cervical operation, most of them due to goiter. We found that the overall rate of transient and permanent recurrent nerve paralysis is considerably increased in patients with previous neck surgery (26% vs. 7%). The combination of ultrasonography and radionuclide scanning can lead surgeons to the site of parathyroid lesions responsible for HPTH in 85% of cases, although frequent nodular goiters can produce pitfalls for correct imaging in iodine-deficient countries. In endemic goiter areas preoperative localization studies can be recommended in patients with primary HPTH—for evaluation of thyroid pathology possibly leading to resection or its accuracy in localizing parathyroid adenomas. These studies also seem justified in patients with previously unsuccessful neck explorations for HPTH.

A simple two-strip method to determine the radiochemical purity of technetium-99m mercaptoacetyltriglycine

Technetium-99m mercaptoacetyltriglycine (MAG3) has been used extensively as a renal function agent for several years. Radioimpurities in the MAG3 kit preparation are not only concentrated and excreted in the kidneys. Therefore proper quality control for renal studies is even more important to make possible a rapid and adequate interpretation of diagnostic studies. The standard method to determine the radiochemical purity is high-performance liquid chromatography (HPLC), which is time consuming and expensive. We set up a new simple thin-layer chromatography (TLC) method based on instant thin-layer silica gel strips as statitionary phase for checking the main impurities, free pertechnetate and reduced hydrolysed 99mTc-colloid. Comparison of TLC and HPLC results showed no significant differences (t-test, P<0.05); the correlation between the results obtained with the two methods in respect of the free pertechnetate content was excellent (r=0.99913). The TLC method was also efficient in determining the percentage of 99mTc-colloid. The main impurity found in 37 routine preparations was free pertechnetate; the mean radiochemical purity was 97.95%. The time required to perform the analysis was less than 20 min. The new TLC system is a cheap, simple, fast, reliable and accurate method for the quality control of the MAG3 kit preparation, and is especially suitable for routine use.

Technetium-99m human immunoglobulin scintigraphy in psoriatic arthropathy: first results

Standard bone scintigraphy [using technetium-99m methylene diphosphonate (MDP)] is widely held to be the most sensitive method for the early detection of psoriatic arthropathy. Preliminary results of this study reveal that 99mTc human immunoglobulin (HIG) scintigraphy demonstrates a typical premature pattern of extradermal psoriatic disease in digits indicative of the early stage of psoriatic arthritis. This pattern was also found in a rare case of psoriatic arthropathy without skin lesions. 99mTc-HIG scintigraphy appears to reveal the initial inflammatory characteristics of later bone lesions. In the advanced stage of psoriatic arthritis, 99mTc-MDP and 99mTc-HIG scans were found to be equally sensitive in the detection of the affected joints. Thus 99mTc-HIG scintigraphy seems to be useful in the early detection of psoriatic arthropathy and also in advanced psoriatic arthritis, as well as for the detection of psoriatic arthropathy without skin lesions.

Surgical therapy for primary hyperparathyroidism in patients with previous thyroid surgery

BACKGROUND In patients with primary hyperparathyroidism (HPTH) and previous thyroid operations, complications of parathyroidectomy are more frequent than in patients undergoing initial neck surgery. The aim of this study was to investigate the value of preoperative imaging with regard to its influence on the surgical strategy. METHODS We retrospectively analyzed 17 patients with primary HPTH and previous thyroid surgery. Preoperatively 16 patients underwent sonography and/or scintigraphy. RESULTS Sonography had an overall accuracy to correctly localize enlarged parathyroid glands of 80%, and scintiscanning had overall accuracy of 78.6%. The accuracy of localization was increased up to 84.6% if both diagnostic procedures were applied. In patients with normal thyroid residues the accuracy of sonography was 85.7%, and it was 100% if scintiscanning was used. CONCLUSIONS Preoperative localization techniques in patients with primary HPTH and previous thyroid surgery have high accuracy. This allows for an imaging-directed operative strategy, thus preventing unnecessary bilateral neck explorations, which carry a high risk of recurrent laryngeal nerve injury.

Failure of labelling of anti-granulocyte antibody

Radiolabelled monoclonal anti-granulocyte antibodies (MAbs) have been used for imaging infection for several years [1-3] and recently also for bone marrow imaging [4]. For routine use the label of choice is technetium-99m (140 keV, 6-h half-life), which is available on a daily basis from a molybdenum-99 generator. MAbs can be labelled with 99mTc in the hospital in a simple procedure using generator eluate and a commercially available instant kit. Due to the protocol used in our department, preparation of the kit and injection for bone marrow imaging are done in the morning (about 8.00-9.00 a.m.) with acquisition 3 h p.i., while preparation and injection for inflammation images are done in the afternoon (about 4.00-5.00 p.m.) with acquisition 16 h p.i. When checking the radiochemical purity of the in-house preparation a poor labelling efficiency was found, especially in the afternoon. This observation led us to look for the reason for this phenomenon. The kit for labelling the MAb BW 250/183 with 99mTc was supplied by Behring Diagnostika (Scintimun Granulozyt, Behring Diagnostika). The kit was labelled according to the instructions given on the package insert [5]. 99mTc-pertechnetate was eluted from a TECEGEN-S generator (Behring Diagnostika), a so-called wet generator, with reference activity of 20 or 8 GBq. The radiochemical purity of 63 proparations was determined by a method suggested by the preducer. Thin-layer chromatography (TLC) was performed using ITLC-SG strips (Gelman-Sciences Inc.) and physiological saline as the developing solvent. In this system the antibody shows an Rf value of 0, the impurities (mainly free pertechnetate) values of 0.9-1.0. The amount of impurity was determined with a TLC scanner. The radiochemical purity was checked prior to injection and if it was lower than 95% the preparation was not used. Out of 63 preparations, 22 were made using generator eluate 6-8 h old, six of them from a generator which had been eluted for the first time (new generator). The remaining 41 were made with an eluate less than 2 h old, six of them from a new generator. Nine preparations showed a radiochemical purity lower than 95%. Only preparations made with an eluate from a generator which had been eluted in the previous 24 h (old generator) and which was not older than 2 h gave an acceptable radiochemical purity. The producer gives no limitation for the generator eluate used for labelling the MAb BW 250/183. Our results show clearly that there is a correlation between the kind of generator eluate used and the radiochemical purity of the final product. The reason might be different amounts of peroxides or the amount of 99Tc in generator eluates [6] combined with the small amount of tin in these kits (24 gg in the final vial). We suggest that this kit should be labelled with generator eluate less than 2 h old from a generator that has been eluted in the last 24 h. This might also be advisable for other antibodies labelled with 99mTc with a similar kit formulation, e.g. MAb BW 431/26 (Anti-CEA MAb).