Parathyroid scintigraphy with 99mTc-MIBI and 123I subtraction: a comparison with magnetic resonance imaging and ultrasonography.

The aim of this study was to evaluate the efficacy of 99mTc-MIBI and 123I subtraction scintigraphy for the detection of abnormal parathyroid glands to be referred for surgical treatment. Thirty-nine consecutive patients, including 35 primary and four secondary cases of hyperparathyroidism, were evaluated. 99mTc-MIBI/123I subtraction scintigraphy (MIBI/I) was performed on all patients, and the results were compared with delayed images of 99mTc-MIBI (D-MIBI), magnetic resonance imaging (MRI) and ultrasonography (US). The overall sensitivity of MIBI/I, MRI, US and D-MIBI was 55.9%, 43.4%, 50.8% and 39.0%, respectively. In cases of single-gland disease, the sensitivity of MIBI/I, MRI, US and D-MIBI was 62.1%, 48.3%, 55.2% and 44.8%, respectively. In cases of multi-gland disease, the sensitivity of MIBI/I, MRI, US and D-MIBI was 50.0%, 37.5%, 46.7% and 36.7%, respectively. In cases of parathyroid adenoma, the sensitivity of MIBI/I, MRI, US and D-MIBI was 71.4%, 50.0%, 71.4% and 50.0%, respectively. In cases of parathyroid hyperplasia, the sensitivity of MIBI/I, MRI, US and D-MIBI was 55.2%, 42.3%, 50.0% and 39.7%, respectively. It is concluded that 99mTc-MIBI/123I subtraction is more useful than the delayed imaging of 99mTc-MIBI, MRI and US.

A novel radiopharmaceutical for detection of malignant melanoma, based on melanin formation: 3-iodo-4-hydroxyphenyl-L-cysteine.

The aim of this study was to develop a new artificial amino acid radiopharmaceutical labelled with radioiodine for detection of malignant melanoma, based on melanin formation. By considering the affinity for tyrosinase, a starting enzyme on the branching point to melanin biosynthesis, 3-[125I]iodo-4-hydroxyphenyl-L-cysteine (125I-L-PC) was synthesized and evaluated biologically. Labelling of 125I-L-PC using the chloramine-T method was carried out conveniently and efficiently in a short period of time, with high specific activity. In a biodistribution study, 125I-L-PC showed a low accumulation in normal tissue and relative retention in B16 melanoma. A high contrast image of peripheral tumour was obtained during autoradiography. During an in vitro accumulation study, inhibition of 125I-L-PC with a tyrosinase inhibitor suggested interaction of this tracer with tyrosinase. It indicates that the uptake mechanism of 125I-L-PC to melanoma tissue was dependent on high tyrosinase activity in melanoma cells. Thus, 125I-L-PC appears to be a promising radioiodinated amino acid radiopharmaceutical for imaging malignant melanoma in relation to melanin formation, namely specific metabolism with high tyrosinase activity.

Technetium-99m tetrofosmin for parathyroid scintigraphy: a direct comparison with (99m)Tc-MIBI, (201)Tl, MRI and US.

The aim of this study was to evaluate the efficacy and role of technetium-99m tetrofosmin for the detection of abnormal parathyroid glands to be referred for surgical treatment. Twenty-eight consecutive patients, including 25 primary and 3 secondary cases of hyperparathyroidism, were evaluated. (99m)Tc-tetrofosmin/(99m)Tc-pertechnetate subtraction scintigraphy (TF/Tc) was performed on all patients, and the results were directly compared with those of (99m)Tc-methoxyisobutylisonitrile (MIBI)/(99m)Tc-pertechnetate subtraction scintigraphy (MIBI/Tc), (201)Tl/(99m)Tc-pertechnetate subtraction scintigraphy (Tl/Tc), magnetic resonance imaging (MRI) and ultrasonography (US). In cases of single-gland disease, the sensitivities of TF/Tc, MIBI/Tc, Tl/Tc, MRI and US were 63.2%, 68.4%, 57.9%, 55.6% and 63.2%, respectively. In cases of multi-gland disease, the sensitivities of TF/Tc, MIBI/Tc, Tl/Tc, MRI and US were 41.7%, 41.7%, 37.5%, 58.3% and 54.2%, respectively. In cases of parathyroid adenoma, the sensitivities of TF/Tc, MIBI/Tc, Tl/Tc, MRI and US were 68.8%, 75.0%, 68.8%, 62.5% and 75.0%, respectively. In cases of parathyroid hyperplasia, the sensitivities of TF/Tc, MIBI/Tc, Tl/Tc, MRI and US were 40.7%, 40.7%, 33.3%, 53.8% and 48.1%, respectively. It is concluded that, for the detection of abnormal parathyroid glands, (99m)Tc-tetrofosmin is as useful as (99m)Tc-MIBI and is more useful than (201)Tl.

[A new protocol of dual energy acquisition on stress 201Tl and rest 99mTc-tetrofosmin myocardial scintigraphy].

We carried out stress 201Tl (Tl) and rest 99mTc-tetrofosmin (TF) myocardial scintigraphy with dual energy acquisition in 24 patients with suspected ischemic heart disease performed coronary arteriography and elucidated the sensitivity of this method. One hour after light meal eating, TF (555 MBq) was injected intravenously at rest and after 3 minutes from injection of TF exercise or pharmacologic stress was performed. During stress Tl (111 MBq) was injected intravenously before end-point or at adequate point of pharmacologic stress. Dual energy acquisition using triple energy windows (TEW) was started after 5 minutes (early) and 4 hours (delayed) from stress. The sensitivity (Sn), specificity (Sp) and accuracy (Ac) in diagnosis of non-infarcted branches by using Tl (early)-TF (rest) and Tl (early)-Tl (delayed) were 79% vs. 53% (Sn), 78% vs. 96% (Sp) and 79% vs. 71% (Ac) respectively. Accordance of uptake score of infarcted region between TF (rest) and Tl (delayed) was 70%. In conclusion, this protocol is seemed to be useful as usual protocol for detection of myocardial ischemia and viability during about only 1 hour.

Evaluation of absorption kinetics of orally administered theophylline in rats based on gastrointestinal transit monitoring by gamma scintigraphy.

The gastrointestinal (GI) transit and absorption of orally administered theophylline, a highly absorbable drug without presystemic elimination, were investigated under fasted and fed conditions using three rats in a crossover study. To evaluate the GI transit rate for each segment in vivo, a noninvasive technique, gamma scintigraphy, was employed using a nonabsorbable compound, (99m)Tc-labeled diethylenetriamine pentaacetic acid (DTPA). Using a gamma scintigraphic technique it is possible to simultaneously evaluate the GI transit and absorption of orally administered drug in the same individual. Theophylline was simultaneously administered along with [(99m)Tc]DTPA to animals in the fasted and fed states. Each GI transit pattern, simulated using the GI transit-kinetic model with a lag time factor, was well fitted to the experimental data. Gastric emptying rate varied in each study, even under the same experimental condition. The GI transit pattern for each segment was highly variable, especially in animals in the fed state. This inconsistency in transit pattern was mainly due to the variability in gastric emptying, which was much slower in animals in the fed compared with the fasted state. However, in spite of a large variability of GI transit kinetics, the plasma concentration-time curves of theophylline were well predicted by the GI transit-absorption model using the individual GI transit parameters obtained in the study. The absorption rate of theophylline was considerably reduced in animals in the fed state, because of the reduction of gastric emptying rate. Analysis using GI transit-absorption model and gamma scintigraphic technique made it possible to estimate the variable absorption kinetics regulated by GI transit with huge variability.

The correlation between 99mTc-MIBI uptake and MIB-1 as a nuclear proliferation marker in glioma--a comparative study with 201Tl.

Technetium-99m methoxy-isobutylisonitrile (MIBI), like thallium-201 (201Tl), is a highly efficient agent for the diagnosis and monitoring of glioma tumors. Although 201Tl uptake is known to be partly associated with proliferative activity, little is known about the correlation between MIBI uptake and proliferation activity in gliomas. The current study was performed to assess the correlation between MIBI uptake and proliferative activities in gliomas, estimated by the monoclonal antibody to Ki-67 antigen (MIB-1) staining method. By comparing the results with those of 201Tl, we determined which tracer would be suitable for estimating proliferative activities. Twenty-four presurgical glioma patients (six with low-grade gliomas, five with anaplastic astrocytomas, and 13 with glioblastomas) were given MIBI and 201Tl SPECT. Early (10 min after injection) and delayed images (3 h after injection) were obtained for both MIBI and 201Tl scintigraphy. SPECT parameters, early ratio (ER), delayed ratio (DR), and retention index (RI) were obtained in both radiopharmaceuticals. All patients underwent subsequent surgical excision, and the specimens were immunostained for MIB-1. The proliferative activity was measured as a percentage positive nuclear area for MIB-1 (MI; MIB-1 index). To evaluate the relationship between the proliferative activity and SPECT parameters, we performed a correlation analysis. MI correlated with the MIBI uptake ratio (r = 0.75 for ER, and r = 0.7 for DR). Both DR and RI of 201Tl also correlated with MI, but weakly (r = 0.6 for DR, and. r = 0.59 for RI). There was no significant correlation between the MIB-1 index and the other parameters. MIBI-uptake parameters demonstrated a stronger positive correlation with the MIB-1 index than that of 201Tl. With the use of MIBI SPECT, we can estimate the proliferative activity of glioma noninvasively.

[Reevaluation of 201Tl-SPECT for patients with solitary pulmonary nodule--comparison study with biopsy method and tumor marker measurement].

We compared the differential diagnostic capabilities of 201Tl-SPECT and biopsy methods and serum tumor marker in 125 patients with solitary pulmonary lesions composed of 87 lung cancer and 38 benign lesions. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of 201Tl-SPECT were 76%, 95%, 97%, 63%, and 82%, respectively. These parameters are similar in biopsy methods. Although sensitivity improved to be 85% by the combination with tumor marker methods, both specificity and accuracy deteriorated to be 55% and 76%. Using combination method with 201Tl-SPECT and biopsy, sensitivity, NPV and accuracy improved to be 84%, 70% and 85%. Based on its high PPV value, 201Tl-SPECT could be useful when biopsy method could not prove lung cancer or in case whose biopsy is considered to be invasive. Because of the lower NPV value owing to false negative cases in some adenocarcinoma, negative 201Tl-SPECT case should be followed up carefully.

[Evaluation of technetium-99m-MIBI scintigraphy in metastatic differentiated thyroid cancer--comparison study with 131I and 201Tl].

Detectability of metastasis in differentiated thyroid cancer using technetium-99m-methoxyisobutyl isonitrile (99mTc-MIBI) was compared with that of 131I and 201Tl. Forty patients after total thyroidectomy were evaluated. The scan results were compared with those of 131I and 201Tl whole body scintigraphy per patient. The positive rate was 68% in 99mTc-MIBI, 84% in 131I, 60% in 201Tl respectively. As to the lymph node metastasis, the positive rates were 56% in 99mTc-MIBI, 78% in 131I, 39% in 201Tl. In lung metastasis, the positive rate was 46% in 99mTc-MIBI, 82% in 131I and 55% in 201Tl. Serum thyroglobulin (Tg) was significantly higher in 201Tl and/or 99mTc-MIBI positive group compared to that of negative group independent of 131I scan results. Although the detectability of both 99mTc-MIBI and 201Tl were inferior to that of 131I, 9 to 22% of metastasis were detected only by these radiopharmaceuticals. Both 99mTc-MIBI and 201Tl, therefore, should be used in cases with high serum Tg even with negative 131I uptake. Basing on the fact there was no prominent difference between 99mTc-MIBI and 201Tl in the detectability of metastasis, 99mTc-MIBI might be more suitable tracer because of better quality image.

A new radiopharmaceutical for the cerebral dopaminergic presynaptic function: 6-radioiodinated L-meta-tyrosine.

Geometric isomers of radioiodinated L-meta-tyrosine, 6-[I-125]iodo-and 4-[1-125]iodo-L-meta-tyrosine (6-I-L-mTyr, 4-I-L-mTyr) were separated by high-performance liquid chromatography . Both 6-I- and 4-I-L-mTyr had high energy-dependent brain accumulation. 6-I- and 4-I-L-mTyr were also metabolically stable and were rapidly excreted through the urine. 6-I-L-mTyr had a predilection for the cerebral aromatic L-amino acid decarboxylase (DOPA decarboxylase), the final enzyme of dopamine biosynthesis. 6-Radioiodinated L-mTyr is a new radiopharmaceutical that can be both useful in assessing cerebral amino acid transport mechanism and quantifying metabolically active DOPA decarboxylase.

rCBF in neurodegenerative diseases as estimated by the autoradiographic (ARG) method and delayed I-123-IMP studies.

A total of 24 patients with a mean age of 45.8 +/- 20.8 were included in the study. The patients were grouped as Control (C), Degenerative Syndromes (DS), Degeneration Associated with External Factors (DEF), Degeneration Associated with Focal Neurologic Lesion (DFN) and Demyelinating Disease (DM). Imaging started 15 minutes for early and 4 hours for delayed scans after i.v. infusion of I-123 IMP. The rCBF was calculated by the IMP autoradiographic (ARG) method. The wash-out ratio (WR) was calculated as the ratio of the Delay/Early count. In the rCBF of the various areas of the brain, significant differences were noted between various disease groups. No correlation was noted between rCBF and WR (r = -0.50). The WR of patients grouped according to various disease processes did not show a significant difference between various areas of the brain. In conclusion, the rCBF was effective in separating both various areas of the brain and disease entities. WR from a delayed study is less useful in neurodegenerative diseases.

The usefulness of Tc-99m MIBI for evaluating brain tumors: comparative study with Tl-201 and relation with P-glycoprotein

PURPOSE: This study was undertaken to determine the usefulness of Tc-99m methoxyisobutylisonitrile (MIBI) in brain tumors compared with TI-201 imaging. The authors evaluated the correlation between MIBI uptake and the presence of P-glycoprotein, and also the relation between MIBI uptake in response to combined radiotherapy and chemotherapy in glioblastoma. MATERIALS AND METHODS: Thirty-four brain tumors composed of 15 glioblastoma multiforme (GBM), 5 anaplastic astrocytomas, 5 low-grade astrocytomas, and 9 metastases were evaluated. Early and delayed images were obtained for MIBI and Tl-201 scintigraphy. P-glycoprotein status in all GBM, 2 anaplastic astrocytomas, 2 low-grade astrocytomas, and 2 metastases were evaluated immunohistochemically. Patients with GBM were divided into an effective and a noneffective group according to the change in tumor size. MIBI uptake indices were compared for these two groups. RESULTS: Both radiopharmaceuticals accumulated in all GBM and anaplastic astrocytomas. In low-grade astrocytomas, only one case showed tracer uptake. In metastasis, two cases showed high uptake on early images and marked washout on delayed images. Uptake ratio values (early uptake ratio and delayed uptake ratio) in all tumors were significantly higher in MIBI than in Tl-201. Immunohistochemical studies showed that the metastases were positive for P-glycoprotein but the GBM were not. In low-grade astrocytomas, a few cells were positively stained. In relation to the therapeutic outcome of GBM, both the early and delayed uptake ratios of MIBI were significantly greater in the noneffective group. CONCLUSIONS: Although diagnostic ability was comparable in MIBI and Tl-201, the imaging quality was better in MIBI. Both radiopharmaceuticals are useful in differentiating low-grade glioma from high-grade glioma. MIBI delayed imaging could also reflect the presence of P-glycoprotein. Intense MIBI uptake was also predictive of a poor clinical outcome in GBM.

Retention of Tc-99m ECD in delayed SPECT of the brain.

We determined the effect of retention on the changes in regional biodistribution of Tc-99m ECD in the brain. A total of 14 cases, 7 normal volunteers and 7 patients with various diagnoses but with very minimal radiologic findings or none were included in the study. SPECT images were taken at 30 min, 1, 2, 3, 4 and 6 hrs after an intravenous injection. Retention rates were calculated in various regions and were corrected according to the time decay of technetium. There was a tendency for the retention rate to increase up to three hours of imaging and then a decrease was noted in most regions of the brain. In the thalamus, increasing retention was noted. In conclusion, Tc-99m ECD retention in the different regions of the brain varies with time. These differences should always be considered when planning and interpreting SPECT quantitative studies.

Brain uptake of iodinated L-meta-tyrosine, a metabolically stable amino acid derivative.

The possibility of using L-meta-tyrosine (L-mTyr) with high metabolic stability and amino acid transport affinity was evaluated. mTyr was first separated into D- and L-isomers with high-performance liquid chromatography and both were labelled with non-carrier-mediated 125I. Biodistribution and pharmacological studies of radioiodinated mTyr in mice and rats were then performed. 125I-L-mTyr showed greater accumulation in the brain and the pancreas. It accumulated in the brain stereospecifically in the in vivo studies and by the L-tyrosine competitive energy dependent transport system in the in vitro studies. It was resistant to deiodination, appeared to have no retention mechanism and was rapidly excreted. 123I-L-mTyr has the potential of an amino acid transport marker, especially in the brain and the pancreas.

Relationship between extraosseous accumulation in bone scintigraphy with 99Tcm-HMDP and histopathology.

We assessed the relationship between 99Tcm-HMDP extraosseous accumulation (EOA), the histopathology of primary lesions and various laboratory findings. In 155 of 4824 patients, 163 EOA were noted. Of these, 33.7% were in the abdomen, 27.6% in the chest, 22.7% in the extremities, 9.8% in the pelvic area and 6.1% in the head and neck area. We found that 72.4% of EOA were due to malignant processes and 27.6% to benign processes. In the abdomen, 36.6% of the EOA were due to hepatocellular carcinoma and intestinal carcinoma. In the chest, 46.7% of EOA were a result of breast carcinoma. In the extremities, 28.7% of the EOA were due to sarcoma. The mean white blood cell count was elevated (8.0 +/- 6.3 x 10(3)) in patients with malignant processes. The mean serum haemoglobin and haematocrit in benign and malignant processes, for both males and females, were below normal values. All other laboratory findings were within normal limits. Significant differences in serum haemoglobin and haematocrit were noted between male and female patients with benign processes (P = 0.04 and P = 0.04, respectively). No other significant differences between benign and malignant processes were noted. Therefore, EOA is more frequently associated with malignant processes of primary lesions and is often accompanied by leukocytosis and anaemia.

Gallium-67 scintigraphy in the treatment and prognosis of acute adult T-cell lymphoma.

The case of a 77-year-old male patient who complained of left upper quadrant pain and progressive vomiting. Laboratory examination showed extremely high lactic acid dehydrogenase (LDH) and adult T-cell leukemia antibody (ATLA). The anatomical studies CT, MRI, US and upper GI series substantiated an omental lymphadenopathy which was causing a circumferential compression of portions of the duodenum and jejunum. Gallium-67 citrate (Ga-67) scintigraphy showed high uptake at LUQ. Ultrasound guided biopsy failed to confirm the diagnosis. Irradiation was performed. Ga-67 scintigraphy had a contributory role in clinical subtyping of the disease, planning of treatment, posttreatment assessment and prognostication of adult T-cell lymphoma.

[Evaluation of brain tumor by 99mTc-MIBI: comparison study with 201Tl and predictivity of therapeutic effect].

We compared the detectability of 99mTc-MIBI and 201Tl-chloride for brain tumor in relationship with histopathology. We also evaluated correlation between therapeutic effect using ACNU, Cisplatine and the degree of MIBI tumor uptake. The subjects were 31 brain tumor histologically confirmed by operation or biopsy. Dual-isotope SPECT technique was performed at both 20 min and 180 min after tracer injection. A tumor to normal lung ratio on both early (ER) and delayed image (DR) and retention index (RI) were calculated. The positive rates of 99mTc-MIBI (90.3% and 77.4%) were comparable to that of 201Tl (90.3% and 80.6%). In the relationship with histopathology, both MIBI and Tl accumulated in 100% of glioblastoma (GBM), metastasis (meta), anaplastic astrocytoma and 25% of low grade astrocytoma on both early and delayed images. On semiquantitative analysis, there were no statistical significance among GBM, meta and anaplastic astrocytoma of ER, DR, RI in the both radiopharmaceuticals. However, both ER and DR in GBM tended to be higher than those of anaplastic astrocytoma. In spite of intense MIBI uptake, GBM patients died within six months except one patient. We concluded that MIBI can be helpful in detecting brain tumor as Tl. MIBI also might be useful in estimating the degree of malignancy in glioma. However, intense MIBI uptake did not mean favorable therapeutic effect in patients with GBM treated with ACNU and Cisplatine.

Application of SPET using technetium-99m sestamibi in brain tumours and comparison with expression of the MDR-1 gene: is it possible to predict the response to chemotherapy in patients with gliomas by means of 99mTc-sestamibi SPET?

Technetium-99m sestamibi (MIBI) is thought to be passively taken up by metabolically active tumour cells and effluxed from them by P-glycoprotein (Pgp). This 170-kDa membrane-bound protein, encoded by the MDR-1 gene, acts as an energy-dependent efflux pump for several antineoplastic agents, resulting in multidrug resistance. For this reason, it is of interest whether the tumour's response to chemotherapy can be predicted by MIBI single-photon emission tomography (SPET). In this study, MIBI SPET was compared with thallium-201 (Tl) SPET using magnetic resonance imaging as a guide in 16 patients with untreated brain tumours [ten glioblastomas (GBs), two anaplastic astrocytomas (AAs), two low-grade gliomas (LGASs) and two metastatic brain tumours) and in four patients who had received treatment for with brain tumours (two GBs, two AAs). In addition, we investigated the expression of the MDR-1 gene and its product Pgp in the same patients, and compared the results with MIBI SPET findings. MIBI, as well as Tl, was highly accumulated and retained in the enhanced region of malignant gliomas. In addition, MIBI SPET yielded sharp and well-contrasted images, and the margin of the tumour was more clearly defined than with Tl SPET due to a good signal-to-noise ratio. Follow-up MIBI SPET in patients who had received therapy showed marked uptake in a patient with malignant transformation, who deteriorated clinically. Patients with no uptake on MIBI SPET showed no sign of recurrence. Semiquantitative analysis of untreated patients showed a relationship between the early uptake index (UI, ratio of average count/pixel in the lesion to that in the contralateral area on early images) and the degree of malignancy (early UI = 1.08+/-0.06 in LGASs, 4.10+/-0.84 in AAs, 5.71+/-3.47 in GBs, and 7.52+/-1.52 in metastatic brain tumours). The retention index (RI, ratio of delayed to early UI) of MIBI was significantly lower than that of Tl in metastatic brain tumours (P<0.05), but not in malignant gliomas. Histological and biological investigation of gliomas showed that the MDR-1 gene and its product Pgp were expressed only in normal endothelial cells and not in tumour cells or proliferating endothelial cells; Pgp tended to decrease as the degree of malignancy rose. Hence, the presence of Pgp and the grade of malignancy were inversely related in gliomas. By contrast, immunohistochemical study showed strong accumulation of Pgp in metastatic brain tumour cells. These histopathological findings and MIBI SPET findings are compatible with experimental data; MIBI was washed out by Pgp. The main cause of chemoresistance is probably not an increasing drug efflux by Pgp in gliomas. Thus, MIBI SPET is useful for detecting the active lesions, but may not be useful for predicting the response to chemotherapy in gliomas.

123I-MIBG myocardial scintigraphy in diabetic patients: relationship with 201Tl uptake and cardiac autonomic function.

PURPOSE: To investigate the influence of diabetic myocardial damage (suspected myocardial damage; SMD) diagnosed by 201Tl-SPECT and diabetic cardiac autonomic neuropathy (AN) on myocardial MIBG uptake in patients with non-insulin-dependent diabetes mellitus (NIDDM). SUBJECTS AND METHODS: Eighty-seven diabetic patients divided into four subgroups: 23 with SMD (+) AN (+); 19 with SMD (+) AN (-); 27 with SMD (-) AN (+); 18 with SMD (-) AN (-), and 10 controls were studied. Both planar and SPECT images were taken at 30 minutes (early) and 3 hours (delayed) after 123I-MIBG injection. The heart to mediastinum uptake ratio (H/M) and washout ratio of 123I-MIBG (WR) were obtained from both planar images. On SPECT images, the total uptake score (TUS) was obtained by the 5 point score method by dividing the myocardium into 20 segments on visual analysis. Similarly, the difference between the 201Tl image and the 123I-MIBG image in TUS was taken as the difference in the total uptake score (delta TUS) representing cardiac sympathetic denervation without SMD. RESULTS: On both early and delayed planar images, the mean H/M value in the subgroups of diabetic patients was significantly lower in the SMD (+) AN (+) group than in the control group, but among those subgroups, there was statistically significant difference between the SMD (+) AN (+) and SMD (-) AN (-) groups only on the delayed images. Regarding the WR value, there was no statistically significant difference among subjects. On SPECT image analysis, the diabetic subgroup with AN or SMD had statistically significant lower values for TUS than those of the control group. Among diabetics, there was a statistically significant differences between SMD [+] AN [+] and SMD [-] AN [-] on both early and delayed images. Similarly, the SMD [+] AN [-] group also had significantly lower values than those of SMD [-] AN [-] on early images. Regarding delta TUS, there was a statistically significant differences between AN [+] subgroups and controls. Similarly, the mean value for delta TUS was much higher in AN [+] subgroups than in AN [-] subgroups with or without SMD in diabetes mellitus. CONCLUSION: 123I-MIBG myocardial uptake is affected by both SMD and cardiac autonomic neuropathy. Based on the finding that delta TUS was much higher in AN [+] subgroups and there was no statistically significant difference between SMD [+] AN [+] and SMD [-] AN [+] subgroups, a decrease in myocardial 123I-MIBG uptake might progress independently of SMD.