Functional Brain Imaging in Cornelia de Lange Syndrome: Case Report and Literature review.

Functional brain imaging with brain single photon emission computer tomography (Brain SPECT) has been used for many years in the evaluation of multiple neuro-degenerative and neuro-developmental disorders. Brain SPECT is a nuclear medicine tomographic study performed with a lipophilic radiopharmaceutical labeled with 99mTc-pertechnetate. It is a cerebral perfusion agent that depicts the global and regional perfusion patterns in the cortical gray matter and subcortical structures. Cornelia de Lange syndrome (CdLS) is a rare neuro-developmental and genetic condition, associated to several malformations. There are a limited number of cases reported in the medical literature and few of them report neuro-radiological and/or neuro-pathologic abnormalities. We report a case of a 15 year old patient, clinically diagnosed at birth with CdLS, who presents limited anatomical findings on Computed Tomography and Magnetic Resonance Imaging. To the best of our knowledge, this is the first report of the Brain SPECT findings in this syndrome.

Leukocyte-technetium-99m uptake in Crohn's disease: does it show subclinical disease?

AIM: To evaluate inflammatory activity in patients with Crohn's disease (CD) using technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) granulocyte scintigraphy. METHODS: Twenty patients (7 male and 13 female) with CD and five healthy volunteers were selected for 99mTc-HMPAO granulocyte scintigraphy. The Crohn's Disease Activity Index (CDAI), blood tests and C-reactive protein (CRP) of each patient were performed 7 d before the scintigraphic images. The leukocytes were labeled according to the International Society of Radiolabeled Blood Elements (ISORBE) consensus protocol and the scintigraphic images, including single photon emission computed tomography, were obtained 30 min and 2 h after injection of the radiolabeled leukocytes. RESULTS: The labeling yield of the leukocytes with the lipophilic complex 99mTc-HMPAO was 55.0% +/- 10%. Six of the 20 patients (30%) presented congruent results for the three parameters investigated (CDAI, Scintigraphic Index and CRP). On the other hand, 14 patients (70%) did not show congruent results. There was no significant correlation between the indices analyzed according to the Spearman test (P > 0.05, n = 20). CONCLUSION: The results suggest that 99mTc-HMPAO-labeled leukocyte scintigraphy could be important for determining inflammatory activity in CD even in the absence of clinical symptoms.

Biodistribution study and identification of inflammatory sites using nanocapsules labeled with (99m)Tc-HMPAO.

PURPOSE: To evaluate the ability of polymeric nanocapsules (NCs) radiolabeled with technetium-99m D,L-hexamethylpropyleneamine oxime (Tc-HMPAO) to identify inflammatory process in an experimental model. METHODS: NCs were prepared by interfacial deposition of preformed biodegradable polymer [poly (D,L-lactic acid) (PLA) and PLA-PEG (polyethyleneglycol)] followed by a solvent displacement. The size and homogeneity, and zeta potential of the NC preparations were determined in a Zetasizer by photon correlation spectroscopy and laser Doppler anemometry, respectively. The NCs radiolabeled with Tc-HMPAO were administered intravenously to Wistar male rats bearing a focal inflammation induced by subplantar injection of carrageenan in the right foot. At preestablished time intervals, the animals were anesthetized, tissues were removed and radioactivity was determined using an automatic scintillation apparatus. RESULTS: The average diameter calculated by photon correlation spectroscopy varied from 216 to 323 nm. The biodistribution studies showed a greater uptake of the PEG surface-modified Tc-HMPAO-NC by the inflamed paws when compared with the respective controls. There was no significant difference in the uptake of conventional Tc-HMPAO-NC and of free Tc-HMPAO by inflamed and control paws. These results indicate that the PLA-PEG Tc-NC showed a higher uptake in inflammation compared with free complex and may be useful as a radiotracer to identify these foci.

PLA-PEG nanocapsules radiolabeled with 99mTechnetium-HMPAO: release properties and physicochemical characterization by atomic force microscopy and photon correlation spectroscopy.

The present work describes the preparation, characterization and labelling of conventional and surface-modified nanocapsules (NC) with 99m Tc-HMPAO. The size, size distribution and homogeneity were determined by photon correlation spectroscopy (PCS) and zeta potential by laser doppler anemometry. The morphology and the structural organization were evaluated by atomic force microscopy (AFM). The stability and release profile of the NC were determined in vitro in plasma. The results showed that the use of methylene blue induces significant increase in the encapsulation efficiency of 99m Tc-HMPAO, from 24.4 to 49.8% in PLA NC and 22.37 to 52.93% in the case of PLA-PEG NC (P<0.05) by improving the complex stabilization. The average diameter of NC calculated by PCS varied from 216 to 323 nm, while the average diameter determined by AFM varied from 238 to 426 nm. The AFM analysis of diameter/height ratios suggested a greater homogeneity of the surface-modified PLA-PEG nanocapsules compared to PLA NC concerning their flattening properties. The in vitro release of the 99m Tc-HMPAO in plasma medium was faster for the conventional PLA NC than for the surface-modified NC. For the latter, 60% of the radioactivity remained associated with NC, even after 12h of incubation. The results suggest that the surface-modified 99m Tc-HMPAO-PLA-PEG NC was more stable against label leakage in the presence of proteins and could present better performance as radiotracer in vivo.

Biodistribution study and identification of inflammation sites using 99mTc-labelled stealth pH-sensitive liposomes.

PURPOSE: To investigate the biodistribution and the ability of stealth pH-sensitive liposomes radiolabelled with 99mTc to identify inflammatory regions in a rat focal inflammation model. METHODS: Preformed glutathione-containing stealth pH-sensitive liposomes were labelled with 99mTc-hexamethylpropylene amine oxime (99mTc-HMPAO). The 99mTc-HMPAO radiolabelled stealth pH-sensitive liposomes (99mTc-SpHL) were administered intravenously in Wistar male rats with inflammation induced by injection subplantar of carrageenan in the right foot. At pre-established time intervals the animals were anaesthetized and tissues were removed and analysed for 99mTc content using an automatic scintillation apparatus. Scintigraphic imaging was also performed after 2, 4 and 8 h of intravenous injection of 99mTc-SpHL. RESULTS: The 99mTc-SpHL was significantly taken up by the spleen (19.21+/-2.98%ID/g at 30 min post-injection). Low radioactivity levels were found in the liver, lungs, and kidney. Moreover, the 99mTc-SpHL uptake was significantly higher in the inflamed foot when compared to the respective control (0.386+/-0.059 and 0.215+/-0.018%ID/g at 2 h post-injection, respectively). As early as 30 min after administration of 99mTc-SpHL, the focus of inflammation could be visualized scintigraphically. The value of the inflammatory and non-inflammatory site radioactivity counting ratio was greater than 5. CONCLUSION: This result indicates that the 99mTc-SpHL presents a high tropism for inflammatory regions and may be useful as a radiopharmaceutical to identify these foci.

SPECT findings in mentally retarded autistic individuals.

The authors examined specific deficits of cerebral blood perfusion in autistic patients as measured with [(99m)Tc]HMPAO single-photon emission computed tomography (SPECT). The study, conducted in an outpatient clinic setting, included a consecutive series of 30 patients with autism and 14 patients with mental retardation but no autism comparable in chronological age, mental age, height, weight, and head circumference. All participants were examined with a comprehensive psychiatric and neuropsychological battery and received a [(99m)Tc]HMPAO SPECT scan. Autistic patients had significantly lower perfusion than the control group in the following brain regions: right temporal lobe (basal and inferior areas), occipital lobes, thalami, and left basal ganglia. The study demonstrated significant perfusion deficits in specific brain areas of moderately to severely mentally retarded autistic patients.

SPECT in Alzheimer's disease: features associated with bilateral parietotemporal hypoperfusion.

OBJECTIVE: To investigate why bilateral parietotemporal hypoperfusion, the typical SPECT pattern of Alzheimer's disease (AD), occurs in some but not in all patients with probable AD. METHODS: We reviewed the SPECT scans of 220 patients presenting with cognitive impairment. Among them, 104 patients fulfilled NINCDS-ADRDA criteria for probable AD, 48 (32 women) with early onset (before age of 65) and 56 (40 women) with late onset of the symptoms. Dementia severity was assessed by the Mini-Mental State Examination. The SPECT scans were classified by visual inspection blind to clinical diagnoses. RESULTS: Bilateral parietotemporal hypoperfusion was more frequent in patients with severe AD, in those with early onset of the symptoms, and in men. Duration of symptoms, type of gamma-camera or radiopharmaceutical agent used were not associated with this SPECT pattern. CONCLUSION: These findings may be useful in the clinical setting and point to heterogeneity of AD according to age at onset.

[Biodistribution of 99mTC-HMPAO in healthy rats and B16 melanoma carriers]. / Biodistribución de 99mTc-HMPAO en ratones sanos y portadores de melanoma B16.

Scintigraphic studies carried out in melanoma patients have demonstrated that the 99mTc-HMPAO complex makes it possible to locate the lesion. A biodistribution and pharmacokinetic study of the 99mTc-HMPAO complex was carried out in B16-melanoma tumor healthy and carrier mice after an intravenous injection. Radioactivity was measured in the liver, kidneys, spleen, stomach, brain, blood and tumor. It was seen that at 15 minutes of the injections, 40% of the total activity distributed in the animal body was recorded in the tumor. An interesting effect observed is an increase in the tissue distribution curves in both experimental groups at 1-2 hours post-injection. According to the seriated imaging study results with 99mTc-HMPAO in B16 melanoma bearing mice, the best image is obtained 10-30 minutes after the injection.