A new method for quantification of hepatobiliary scintigraphy using 99mTc-mebrofenin. A comparative study

A method based upon the application of mathematical techniques of deconvolution on the classical compartmental model for the quantitative study of liver function from hepatobiliary scintigraphy using 99mTc-mebrofenin data is proposed. The theory in which the method is based upon is presented and a comparison with a published methodology of obtaining the hepatic extraction after scintigraphic sudies has been performed using the results on 36 rats studies obtained with the two methods. A highly significant correlation between the two techniques was verified. The characteristics of the two methodologies, the proposed one based upon a theoretical approach and the other one on an empirical approximation are discussed. Comments are made on the interest and limitations of the presented technique that may be an useful tool for the evaluation of hepatic insufficiency.     

A new method for brain functional study using Tc-99m HMPAO SPECT

The distribution of 99mTc-HMPAO in brain is in proportion to regional cerebral blood flow (rCBF) and can be interpreted as functional mapping. To evaluate local changes in CBF during neuropsychological testing, we developed a new subtraction method using HMPAO and SPECT. With patients resting, 15 mCi of HMPAO was injected and the first acquisition was performed, lasting a total of 10 minutes. Soon after the end of the first scan, patients were requested to undergo Buschke's memory test or to repeat words or numbers (repetition test). During the task, an additional 15 mCi of HMPAO was injected using the same position as in the first scan, and a second acquisition was started. A functional image was made by subtracting the image in the first scan from that in the second. In two patients with transient global amnesia and two normal controls, Buschke's memory test was performed in combination with SPECT. A Relative increase in activity was seen in the thalamus, subthalamic area, hippocampus, and some cortical areas, apparently reflecting local functional change induced by the memory task. In two patients with moderate Alzheimer's disease with severe memory loss, no increase was detected in these areas. In one patient with aphasia, the repetition test with SPECT was correlated with the WADA test and dichotic listening test, and good agreement was obtained. In conclusion, our new SPECT technique is useful in detecting alterations in rCBF during mental activity and can be applied to neurophysiological studies.     

A new method for pharmacokinetic analysis of 99mTc-GSA using two-compartment and two-parameter model

Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (99mTc-GSA) is a liver scintigraphy agent which binds to asialoglycoprotein receptor in hepatocyte. Twenty-six patients with liver dysfunction were examined with 99mTc-GSA liver scintigraphy using two-compartment and two-parameter model (2C2P model). The 99mTc-GSA was assumed to move within two compartments (whole blood and liver). k1 and k2 were parameters which represented transfer rate constant from blood to liver, and from liver to blood, respectively. Two differential equations based on 2C2P model were integrated, so that k1, k2, k1/k2 and VLmg were estimated from the time-activity curves of the heart and liver. VLmg was computed as maximum amount of 99mTc-GSA binding to liver. The results were compared with the liver function tests and the conventional 99mTc-GSA indices: HH15, LHL15, and LU15. k1/k2 and VLmg values had positive correlation with the result of the serum liver function tests, Plt., T.Bil., ChE, GOT, LDH, ALP and gamma GTP. It is concluded that this new method using 2C2P model is not invasive and simplest in the 99mTc-GSA liver scintigraphies, and may be useful in evaluating liver function.     

A routine method for using sodium iodide to stabilize sodium pertechnetate [99Tcm] dispensed for the preparation of 99Tcm-exametazime.

When preparing 99Tcm-exametazime, it is important to use sodium 99Tcm-pertechnetate that is less than 2 h old. The addition of sodium iodide (NaI) to 99Tcm-pertechnetate is known to extend this time to 6 h. This paper describes a technique for implementing this in routine practice. Sterile kits consisting of 440 micrograms NaI and 1.0 ml sodium chloride injection in a vial with a nitrogen atmosphere were prepared and stored at room temperature, 4 degrees C and -22 degrees C. Titrimetric analysis of iodide showed that under each storage condition, kits were stable for 8 weeks. To determine the effectiveness of the kits, the radiochemical purity (RCP) of 99Tcm-exametazime was measured by high-performance liquid chromatography (HPLC). The validity of this technique was determined by simultaneous analysis with the conventional thin-layer/paper chromatography (TLC/PC) technique on 24 occasions, over a range of RCP (94.5-54.6%). Radiochemical purities measured by HPLC and TLC/PC were 81.2 +/- 10.2 and 81.5 +/- 10.5%, respectively, and did not differ significantly (P greater than 0.30). The correlation between the techniques was high (r = 0.98). 99Tcm-exametazime was prepared using 1 h-old 99Tcm-pertechnetate, 6 h-old 99Tcm-pertechnetate and 6 h-old 99Tcm-pertechnetate dispensed in a NaI kit. At the recommended expiry time for this radiopharmaceutical, i.e. 30 min after preparation, RCPs were found to be 88.4 +/- 2.4, 80.9 +/- 2.0 and 89.3 +/- 3.0%, respectively (n = 5 for each technique).(ABSTRACT TRUNCATED AT 250 WORDS)     

Brain perfusion SPECT imaging before and during the acetazolamide test using 99mTc-HMPAO

A new method using brain perfusion 99mTc-HMPAO SPECT imaging was developed for evaluating cerebral perfusion reserve by the acetazolamide test with a short period. The first SPECT study was carried out for 13.5 min to obtain SPECT images at the resting state after 3 min postinjection of 555 MBq (15 mCi) of 99mTc-HMPAO. At the same time as the start of the first SPECT study, 1 g of acetazolamide was intravenously injected. Immediately after the stop of the 1st SPECT study, 925 MBq (25 mCi) of 99mTc-HMPAO from the same vial as in the first study was additionally injected. Three minutes later the second SPECT study was carried out for 10 min. After reconstruction the tomographic images in the first study were subtracted from the images in the second study to obtain those during the acetazolamide test after correction of the time differences in data acquisition between the two studies. This subtraction technique gives independent brain perfusion SPECT images before and during the acetazolamide test. Besides, the regional flow changes during the test were quantitatively analyzed. In conclusion this method seems to be practically useful for evaluating regional brain perfusion before and during drug treatments as a consecutive study with a short period of approximately 30 min.     

Cerebrovascular reactivity to acetazolamide in alert patients with cerebral infarction: usefulness of first-pass radionuclide angiography using 99m Tc-HMPAO in monitoring cerebral haemodynamics

Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were studied in 75 patients with cerebral infarction. All patients were alert with the symptoms of hemiparesis and/or aphasia, and were divided into two groups: 42 patients had occlusion or stenosis of >75% at the internal carotid artery or main trunk of middle cerebral artery; and 33 patients did not. Hemispheric mean CBF was measured by performing first-pass radionuclide angiography using 99mTc-hexamethylpropylene amine oxime. CVR was measured as the percentage change from the baseline mean CBF value after the administration of 500 mg acetazolamide. The CVR in both groups was significantly impaired (5.2+/-6.3%, P<0.001 and 7.7+/-6.1%, P<0.01, respectively) compared with normal controls (14.7+/-3.3%), although the mean CBF was not significantly reduced compared with age-matched controls. In the 12 patients with unilateral carotid occlusion, five patients with good collateral flow via the anterior communicating artery showed preserved CVR (11.0+/-7.8%), but those without did not (1.6+/-7.0%). CVR is impaired in alert patients with cerebral infarction, although the mean CBF is not reduced, and good collateral flow via the anterior communicating artery in patients with carotid occlusion may be a sign of well-preserved haemodynamic status.     

A new method for radiolabeling of Gelfoam particles with 99mTc

Embolization of the spleen and other organs using Gelfoam has recently gained acceptance as a therapeutic procedure. A simple non-invasive determination of the placement of Gelfoam particles is needed and this requires labeling Gelfoam with radionuclides. We have developed a simple, reliable reproducible, and inexpensive method of labeling Gelfoam with 99mTc using commercial sulfur colloid kits. Optimal reaction conditions include room temperature incubation for 60 min at 12 rpm rotation. In vitro stability indicated no loss of 99mTc activity up to 3 h post labeling. Imaging of intra-arterially placed 99mTc Gelfoam at 1 h and 24 h in animals and humans has consistently produced well-defined images of the radioemboli.     

SPECT evaluation of brain perfusion reserve by the acetazolamide test using Tc-99m HMPAO

This report describes a new approach to the evaluation of brain perfusion reserve using Tc-99m HMPAO SPECT. Consecutive brain Tc-99m HMPAO SPECT studies before and after acetazolamide (Diamox) administration were performed within 30 minutes on 19 patients with significant vascular occlusive lesions. Thirteen patients showed decreased perfusion reserve and four patients maintained perfusion reserve in the affected vascular territories after Diamox administration, providing additional information to baseline Tc-99m HMPAO SPECT in 17 (89%) patients. Although flow augmentation post-Diamox was underestimated, possibly due to the nonproportionality of Tc-99m HMPAO activity to true blood flow, significant changes in the brain perfusion pattern were both visually and quantitatively determined using an image subtraction technique. This consecutive Tc-99m HMPAO SPECT technique seems to be of practical use for the evaluation of brain perfusion reserve and for the improvement of the sensitivity of detecting pathologic areas.     

Quantitative measurement of regional cerebrovascular reactivity to acetazolamide using 123I-N-isopropyl-p-iodoamphetamine autoradiography with SPECT: validation study using H2 15O with PET.

A simplified technique using (123)I-N-isopropyl-p-iodoamphetamine ((123)I-IMP) autoradiography (ARG) with SPECT has been proposed recently for quantifying regional cerebral blood flow (rCBF). To validate the accuracy of (123)I-IMP-ARG for quantifying regional cerebrovascular reactivity (rCVR) to acetazolamide, we compared rCVR determined using (123)I-IMP-ARG with that determined using H(2)(15)O PET. METHODS: Thirty-nine patients with chronic stenoocclusive disease in a unilateral major cerebral artery underwent SPECT and PET studies before and after intravenous administration of acetazolamide. The rCBF images in the 4 conditions in each patient were calculated according to the ARG method. The same standard input function and the same distribution volume of 35 mL/mL were used in the calculation of rCBF images using the (123)I-IMP-ARG method at resting state and with acetazolamide challenge. One large cortical region of interest (ROI) for a unilateral middle cerebral artery territory was bilaterally determined on each standardized summed rCBF image. On the basis of the rCBF values in each ROI, rCVR to acetazolamide was calculated as follows: rCVR (%) = ([acetazolamide challenge rCBF - resting rCBF]/resting rCBF) x 100. RESULTS: Significant correlation was observed between rCVR values obtained using (123)I-IMP-ARG and H(2)(15)O PET methods in the 78 ROIs examined in the 39 patients (r = 0.820; P < 0.0001). When a rCVR lower than the mean - 2 SD of values obtained in healthy volunteers (18.4% for (123)I-IMP-ARG and 18.2% for H(2)(15)O PET) was defined as reduced, and when the H(2)(15)O PET method was assumed to represent the true determinant of rCVR, (123)I-IMP-ARG was 90% sensitive and 92% specific and displayed an 87% positive predictive value for detecting patients with reduced rCVR. CONCLUSION: These findings demonstrate that (123)I-IMP-ARG methods accurately quantify rCVR and can adequately define subgroups of patients with reduced rCVR.     

A new electrophoretic method for determining ligand: technetium stoichiometry in carrier free 99mTc-radiopharmaceuticals.

An electrophoretic procedure is outlined for the determination of the number of ligands bound to technetium-99m radiopharmaceuticals. The approach involves use of ligands that will complex technetium in a similar fashion but that differ in charge. This approach was applied experimentally to dimercapto ligands in which the ligating sulfur atoms are separated by a flexible three-carbon chain (1,3-dimercapto compounds). Two such ligands studied are 1,3-dimercaptopropane (DMP) and dihydrothioctic acid (DHTA). The Tc compound of DHTA migrates much farther on electrophoresis than the Tc complex of DMP. However, when TcO4- is reduced by SnCl2 or NaBH4 in the presence of equimolar quantities of DHTA and DMP, a new compound is formed being twice as abundant as either the TcDMP or the TcDHTA compound and migrating an intermediate distance. The formation of this new complex and the 1:2:1 distribution indicates that two 1,3-dimercapto compounds are attached to the Tc-center in all three compounds.     

Assessment of cerebral perfusion and cerebrovascular reserve in insulin-dependent diabetic patients without central neurological symptoms by means of 99mTc-HMPAO SPET with acetazolamide.

The detection of subclinical abnormalities in cerebral blood flow could be of great value in identifying diabetic patients at risk of stroke. The aim of this study was to assess the contribution of semiquantified post-acetazolamide technetium-99m hexamethylpropylene amine oxime single-photon emission tomography (99mTc-HMPAO SPET) in 15 diabetic patients with no clinical history of central neurological disease. After baseline 99mTc-HMPAO SPET, a second SPET scan was acquired after activation of the cerebrovascular reserve (CVR) with an injection of 1 g of acetazolamide (post-ACZ SPET). Semiquantitative analysis was made in 16 regions of interest (ROIs) drawn for each of the three supratentorial slices selected, and in two ROIs in the infratentorial slice. The CVR was calculated in each ROI by subtracting the decay-corrected baseline images from those obtained in the post-ACZ SPET and expressed as the percent increase in the average counts between the two scans. Baseline perfusion and CVR values in the study group were compared with the corresponding values in a control group. Of 750 cortical ROIs studied, 332 showed a decreased CVR (44.3%). The baseline perfusion SPET study showed hypoperfusion in 65 ROIs (8.6%) and hyperperfusion in 56 (7.4%). Of the 65 hypoperfused regions, 66.2% had a normal CVR and 33.8% had a decreased CVR, whereas of the 56 hyperperfused regions, 51.8% had a CVR within normal limits and 48.2% showed a decreased CVR. In conclusion, in comparison with baseline 99mTc-HMPAO SPET, the ACZ activation test provided additional information in the study of cerebrovascular impairment, and allowed characterisation of the subclinical abnormalities in the population studied. The technique may therefore prove useful in evaluating future preventive strategies for stroke in diabetic patients.     

A new approach in radionuclide imaging to ureteric peristalsis using 99Tcm-MAG 3 and condensed images.

A new method for the evaluation of ureteric peristalsis is described. Standard, dynamic renal scintigraphy was carried out using 99Tcm-MAG 3 in 59 patients. Time-activity curves and condensed images over the ureter area were created simultaneously. A six-grade scale (O-V) was chosen for the classification of ureteral function. The results obtained were compared with parameters of renographic curves and other clinical findings. In a group of 13 patients, two different renal radiopharmaceuticals were used: 131I-OIH and 99Tcm-DTPA. The results show that the new method is suitable for the assessment of ureteral disorders, and has some advantages compared with previously described methods. 99Tcm-MAG 3, with a better target-to-background ratio compared to 131I-OIH and 99Tcm-DTPA, is the most suitable radiopharmaceutical for this purpose.     

Sequential 99mTc-hydrazinonicotinamide-annexin V imaging for predicting response to chemotherapy.

This study was undertaken to evaluate changes in relative (99m)Tc-hydrazinonicotinamide (HYNIC)-annexin V tumor uptake over time in patients undergoing chemotherapeutic treatment at baseline and at 5-7 h and 40-44 h after treatment initiation. Imaging results are related to clinical outcomes, as assessed with response evaluation criteria in solid tumors (RECIST). METHODS: We prospectively included 20 patients (11 men and 9 women; mean age, 59.8 y; range, 22-75 y) scheduled for chemotherapy (n = 19) or bisphosphonate treatment (n = 1). Curable disease was present in 5 patients. The other patients had metastatic disease and were treated in a palliative setting. Three of the 20 enrolled patients were excluded from analysis: 1 patient ultimately refused the proposed chemotherapy treatment; because of difficulties with the labeling procedure, 1 patient did not receive a pretreatment scan; and 1 patient presented with an allergic reaction (rash and nausea) to the (99m)Tc-HYNIC-annexin V formulation. The remaining 17 patients underwent 3 scintigraphic scans with (99m)Tc-HYNIC-annexin V: before treatment and 5-7 h and 40-44 h after treatment initiation. The tumor response was evaluated with RECIST and related to observed changes in the ratios of tumor activity to background activity for the largest known lesion; values exceeding 25% the baseline value on either the 5- to 7-h scan or the 40- to 44-h scan were considered significant. RESULTS: With the proposed sequential imaging protocol and a 25% change threshold, responders to treatment could be separated from nonresponders with a 94% accuracy (16/17 patients). CONCLUSION: Sequential (99m)Tc-HYNIC-annexin V imaging may allow for assessment of the response to chemotherapy within 3 d after treatment initiation.     

18F-FDG PET and 99mTc-sestamibi scintimammography for monitoring breast cancer response to neoadjuvant chemotherapy: a comparative study.

Presurgical neoadjuvant chemotherapy has shown promise in the treatment of locally advanced breast carcinoma (LABC). Response assessment by clinical examination and mammography is difficult. This study evaluated and compared fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and technetium-99m sestamibi scintimammography (SMM) as potential methods for the early assessment of tumour response to neoadjuvant chemotherapy in patients with LABC. Seven patients underwent PET and SMM [planar and single-photon emission tomography (SPET)] before beginning chemotherapy, after the first and second cycles of chemotherapy and after completing chemotherapy prior to surgery. PET and SMM results were evaluated visually and semi-quantitatively by calculating standardised uptake values (SUV) and tumour/lung ratios in the initial and subsequent studies. The findings were correlated with the initial clinical and mammographic findings and the final histopathological diagnoses. There was a highly significant correlation between SUVmean, SUVmax and the tumour/lung ratio determined with SMM-SPET in the studies performed before and during neoadjuvant chemotherapy. All three patients with complete remission showed decreasing FDG and sestamibi uptake as early as 8 days after therapy. In the presurgical study, increased sestamibi and FDG uptake was no longer evident. Three patients had partial remission with clearly reduced but persisting focal FDG and sestamibi uptake after neoadjuvant therapy. One patient who did not respond to therapy had unchanged intense tracer uptake during chemotherapy that was evident with both techniques. An early decline in glucose metabolism or sestamibi uptake 8 days after beginning therapy did not necessarily predict complete tumour remission in the further course of chemotherapy. On the other hand, increased tracer uptake after the first cycle did not exclude a partial tumour response. After the second chemotherapeutic cycle both techniques were able to distinguish between complete and partial/no response. There was a good correlation between preoperative FDG and sestamibi uptake and the histopathologically determined tumour size. However, small residual invasive tumours in patients with clinically complete remission could not be visualised with either technique. The preliminary data demonstrate that sestamibi SMM is as useful as FDG-PET for the monitoring of tumour response to neoadjuvant chemotherapy.     

Evaluation of delayed appearance of acetazolamide effect in patients with chronic cerebrovascular ischemic disease: feasibility and usefulness of SPECT method using triple injection of ECD.

The purpose of this study was to verify the feasibility and usefulness of a new SPECT method, called triple injection of (99m)Tc-ethylcysteinate dimer (TIE), in evaluation of the delayed or poor appearance of acetazolamide (ACZ) effects in patients with chronic cerebral ischemic disease. METHODS: Three equal-volume splits of (99m)Tc-ethylcysteinate dimer were intravenously administered, and 1,000 mg ACZ were used as a vasodilator. A middle cerebral artery territory in the lateral ventricle was used as a region of interest. The data at rest and at 7.5 and 20 min after ACZ challenge (ACZ 7.5 and ACZ 20, respectively) were obtained by dynamic SPECT, and a time response curve to ACZ was obtained through the relative ratio of regional counts to the data at rest, not through regional cerebral blood flow. Nine cases of complete occlusion of the internal carotid artery (IC) and 6 cases of severe IC stenosis were analyzed. RESULTS: In 12 healthy volunteers (24 cerebral hemispheres) using a placebo (negative control), the values at rest and at rest 7.5 and rest 20 (corresponding to ACZ 7.5 and ACZ 20, respectively) were 100%, 100.4% +/- 2.8%, and 99.6% +/- 3.6%, respectively, indicating the accuracy of the TIE method. In a positive control using 24 normal cerebral hemispheres, prompt maximal vasoreactivity at ACZ 7.5 (124.5% +/- 8.0%) was confirmed, as was continuous vasoreactivity until ACZ 20 (130.1% +/- 12.8%). The values between ACZ 7.5 and ACZ 20 were not statistically different. Patients with complete IC occlusion exhibited a poor response at ACZ 7.5 despite a normal response at ACZ 20 (delayed response). Furthermore, in patients with severe IC stenosis, restoration of cerebrovascular reactivity after carotid endarterectomy was confirmed not only at ACZ 20 but also at ACZ 7.5. CONCLUSION: The TIE method using SPECT may be a potentially useful and sensitive strategy in clinical evaluation of the delayed or poor appearance of ACZ effects in patients with chronic cerebrovascular ischemic disease.     

New preparation method for 99mTc-phytate.

A new method is described in which Pt-Sn or Sn-Sn electrodes are used to activate 99mTcO4-. The 99mTc is incorporated into phytic acid by stannous ion released from a tin anode by the corrosive reaction. The most suitable pH for labeling phytic acid by this method was below 5 and the 99mTc-phytate formed could be precipitatedd with Ca+2 at a pH above 3.5. Though 99mTc-phytate is soluble in aqueous solution, it forms an insoluble species with Ca+2 in vivo and is trapped in the reticuloendothelial system. More than 93% of the 99mTc-phytate localized in the liver of mice; here its biologic half-time is about 112 hr. The 99mTc-phytate prepared by this method promises to be useful as a liver-scanning agent. Since our method does not require an applied electric potential, it appears to be one of the most convenient methods for labeling compounds with 99mTc.     

A new semiquantitative method for comparing brain tumor uptake of Tc-99m sestamibi and TI-201.

PURPOSE: We describe a new method for measuring brain tumor uptake of TI-201 and Tc-99m sestamibi (MIBI) that permits the semiquantitative comparison of tracer uptake to yield comparable "tumor bulk" ratios. We tested this method in patients treated recently and remotely with chemotherapy to determine if this method could identify differences between these two patient groups. METHODS: Eleven patients with high-grade astrocytoma underwent TI-201 and Tc-99m MIBI SPECT. Each patient received 5 mCi TI-201 intravenously followed by SPECT using a dual-head gamma camera. This was immediately followed by an intravenous injection of 20 mCi Tc-99m MIBI and repeated SPECT. Four patients had recent therapy (from 1 day to 6 weeks before SPECT) and seven had remote treatment (>1 year before SPECT). Regions of interest were outlined in the tumor area using a computer-automated program to include all counts above background activity. Tumor activity counts were obtained from this region of interest. The tumor region of interest was mirrored to the contralateral uninvolved cerebral hemisphere to obtain background control count activity. A hypothetical volume of the number of pixels with background count activity necessary to constitute the tumor count activity (tumor bulk) was calculated using the ratio of total tumor counts (Ct), subtracting background (Cb), and dividing by the average counts per pixel in the control region (Cab). This was multiplied by the number of pixels (P), the pixel volume (Vp), and summed over all sections (i) involved with tumor. This method yields the equation tumor bulk = RESULTS: The mean Tc-99m MIBI to TI-201 tumor bulk ratio was 1.03 (range, 0.81 to 1.12) in four patients who had recently received chemotherapy. The mean Tc-99m MIBI to TI-201 tumor bulk ratio was 1.55 (range, 1.46 to 1.64) in seven patients who had remote therapy. The difference in the Tc-99m MIBI to TI-201 tumor bulk ratio between the two groups was significant (P = 0.0001). Patients who received recent chemotherapy had relatively lower Tc-99m MIBI uptake compared with TI-201. In remotely treated patients, uptake of the Tc-99m MIBI was greater compared with TI-201. CONCLUSION: This method allows semiquantitative comparison of different tracer uptake values independent of tracer dose and reduces the variability in drawing a region of interest when measuring tumor uptake. Among the patients studied, those who had recent chemotherapy showed a low Tc-99m MIBI to TI-201 ratio. This method of measuring "tumor bulk" can provide a useful index of viable tumor size in evaluating early tumor response and during ongoing chemotherapy.