Functional imaging studies of cognition using 99mTc-HMPAO SPECT: empirical validation using the n-back working memory paradigm.

PURPOSE: Functional activation protocols are widely applied for the study of brain-cognition relations. Only few take advantage of the intrinsic characteristics of SPECT, particularly those allowing cognitive assessment outside of the camera, in settings close to the standard clinical or laboratory ones. The purpose of the study was to assess the feasibility of a split-dose activation protocol with (99m)Tc-HMPAO using low irradiation dose. MATERIALS AND METHODS: A two-scans protocol was applied to 12 healthy young volunteers using 270 MBq of (99m)Tc-HMPAO per scan, with each image associated to a particular experimental condition of the verbal n-back working memory task (0-back, 2-back). Subtraction method was used to identify regional brain activity related to the task. RESULTS: Voxel-wise statistical analysis showed left lateralized activity associated with the 2-back task, compared to the 0-back task. Activated regions, mainly prefrontal and parietal, were similar to those observed in previous fMRI and (15)O-PET studies. CONCLUSION: The results support the use of (99m)Tc-HMPAO SPECT for the investigation of brain-cognition relations and demonstrate the feasibility of optimal quality images despite low radiopharmaceutical doses. The findings also acknowledge the use of HMPAO as a radioligand to capture neuro-energetic modulations linked to cognitive activity. They encourage extending the application of the described activation protocol to clinical populations.

Database of normal human cerebral blood flow measured by SPECT: I. Comparison between I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD as referred with O-15 labeled water PET and voxel-based morphometry.

OBJECTIVES: Three accumulative tracers, iodine-123-labeled N-isopropyl-p-iodoamphetamine (I-123-IMP), technetium-99m-labeled hexamethylpropyleneamineoxime (Tc-99m-HMPAO), and technetium-99m-labeled ethyl cysteinate dimer (Tc-99m-ECD) are widely used to measure cerebral blood flow (CBF) in single-photon emission computed tomography (SPECT). In the present study, normal regional distribution of CBF measured with three different SPECT tracers was entered into a database and compared with regional distribution of CBF measured by positron emission tomography (PET) with H2(15)O. The regional distribution of tissue fractions of gray matter determined by voxel-based morphometry was also compared with SPECT and PET CBF distributions. METHODS: SPECT studies with I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD were performed on 11, 20, and 17 healthy subjects, respectively. PET studies were performed on 11 healthy subjects. Magnetic resonance (MR) imaging studies for voxel-based morphometry were performed on 43 of the 48 subjects who underwent SPECT study. All SPECT, PET, and MR images were transformed into the standard brain format with the SPM2 system. The voxel values of each SPECT and PET image were globally normalized to 50 ml/100 ml/min. Gray matter, white matter, and cerebrospinal fluid images were segmented and extracted from all transformed MR images by applying voxel-based morphometry methods with the SPM2 system. RESULTS: Regional distribution of all three SPECT tracers differed from that of H2150 in the pons, midbrain, thalamus, putamen, parahippocampal gyrus, posterior cingulate gyrus, temporal cortex, and occipital cortex. No significant correlations were observed between the tissue fraction of gray matter and CBF with any tracer. CONCLUSION: Differences in regional distribution of SPECT tracers were considered to be caused mainly by differences in the mechanism of retention of tracers in the brain. Regional distribution of CBF was independent of regional distribution of gray matter fractions, and consequently the blood flow per gray matter volume differed for each brain region.

Methylene blue-enhanced stability of (99mTc)HMPAO and simplified quality control--a comparative investigation.

(99mTc)HMPAO is a radiopharmaceutical used for SPECT imaging of regional cerebral perfusion and for labeling cellular blood elements. The addition of methylene blue enhanced the stability of lipophilic (99mTc)HMPAO complex up to 3 h after reconstitution, 86.9+/-4.2% compared to 49.8+/-8.9% for the non-stabilised complex and persists over time (86.2+/-3.5% after 15 min compared to 78.2+/-4.0% after 3 h). The method widely used for estimation of radiochemical purity is a standard chromatographic procedure which is quite time-consuming taking about 30 min. Comparison of the more rapid and simple solvent extraction method with octanol, which needs only about 10 min to complete. showed a good correlation with the chromatographic method (84.4+/-4.4% compared to 89.1+/-4.3%). Using ethyl acetate as solvent instead of octanol gave a slightly higher extraction rate of the lipophilic complex (91.5+/-5.5% compared to 89.1+/-4.3%). Further, the ethyl acetate extraction method results in an overestimation, extracting partly secondary complex. It is confirmed, that the stability of the lipophilic (99mTc)HMPAO complex can be increased with methylene blue. The octanol extraction method, using higher extraction volume (up to 3 ml), is recommended as a fast and efficient approach for the quality control in daily clinical routine.

Validation of a column method for technetium-99m exametazime quality control.

OBJECTIVE: The purpose of this study was to investigate if an octadecyl (18C) minicolumn could be applied successfully for quality control of 99mTc exametazime (HMPAO). METHODS: The 18C column system using saline eluent was validated against the Whatman 17 method in calculating the percent radiochemical purity of 99mTc-HMPAO. The behavior of 99mTc-pertechnetate (99mTc04-) and hydrolyzed-reduced 99mTc (99mTc02) on the column was examined, as well as method reproducibility. RESULTS: The column method is reproducible and yields results that are highly comparable to the Whatman 17 method. Technetium-99m-pertechnetate is associated with the eluent, and some 99mTc02 is retained by the column but this level is insignificant to the final patient dose. CONCLUSION: The minicolumn system is safe, simple, rapid and reliable for the quality control analysis of routine 99mTCHMPAO preparations.