Thomas Leitha

Myocardial m-[123I]Iodobenzylguanidine Scintigraphy for the Assessment of Adrenergic Cardiac Innervation in Patients With IDDM: Comparison With Cardiovascular Reflex Tests and Relationship to Left Ventricular Function

Cardiac imaging using m-[123I]iodobenzylguanidine (mIBG) reflects sympathetic myocardial innervation. In patients with insulin-dependent diabetes mellitus (IDDM), the following were studied: 1) the prevalence of derangements of cardiac autonomic innervation as detected by mIBG scintigraphy in comparison with cardiovascular reflex tests and 2) the relationship between adrenergic cardiac innervation and left ventricular (LV) function. Twenty-four patients with IDDM without overt heart disease were studied after silent coronary artery disease was excluded by 201Tl scintigraphy. Cardiac innervation was evaluated by both mIBG scintigraphy (tomographic imaging) and cardiovascular reflex tests. Systolic (ejection fraction [EF] percentage) and diastolic (peak filling rate [PFR] defined as end-diastolic volumes per second [EDV/s]) LV function were determined by equilibrium radionuclide angiography at rest and during bicycle exercise. mIBG scintigraphy was also performed in 10 control subjects. All control subjects exhibited a normal myocardial mIBG distribution. Among diabetic patients, only six had normal mIBG scans (group 1), whereas 18 had evidence of regional adrenergic denervation (group 2). Reflex tests suggested cardiac autonomic neuropathy in only seven of these patients (P < 0.01 vs. mIBG). All patients had a normal EF at rest. However, group 2 showed an impaired response to exercise as indicated by a smaller increase in EF (5 ± 6 vs. 13 ± 5%, P < 0.05) and a lower PFR (5.9 ± 0.8 vs. 7.3 ± 1.2 EDV/s, P < 0.01). Myocardial mIBG scintigraphy reveals that in patients with IDDM, sympathetic myocardial dysinnervation is much more common than previously thought. Furthermore, subclinical LV dysfunction is related to derangements of adrenergic cardiac innervation.

Comparison and histopathological correlation of three parathyroid imaging methods in a population with a high prevalence of concomitant thyroid diseases

The aim of this prospective study was to evaluate the diagnostic utility of a technetium-99m sestamibi dual-phase protocol enhanced by single-photon emission tomography (SPET) and semiquantitative analysis in comparison to established preoperative staging procedures in patients with primary hyperparathyroidism. Twenty-eight (50%) out of 56 patients had superimposed thyroid disease, and 12 patients had previously undergone neck surgery. Visual and semiquantitative analysis of planar99mTc-sestamibi dual-phase imaging, SPET of the delayed phase, ultrasonography, and thallium-201 chloride-technetium-99m pertechnetate subtraction scintigraphy was further correlated with the histopathological examination of the surgical specimens.99mTc-sestamibi dual-phase imaging achieved the highest sensitivity for side localization and precise localization compared with201Tl-99mTc subtraction scintigraphy and ultrasonography, but the differences reached statistical significance only in comparison to ultrasonography. Semiquantitative analysis did not enhance sensitivity. Adenoma detection by99mTc-sestamibi dual-phase imaging was only correlated to serum calcium levels and osteocalcin, not to cell density or oxyphil cell count (SPET yielded additional information for the exact topographical localization of the parathyroid tumour in 22 (39%) patients with superimposed thyroid disease or previous neck surgery but did not enhance the overall detection rate.

Clinical manifestations and diagnostic approach to metastatic cancer of the mandible

In a 12-month period, metastatic cancer was diagnosed in eight patients. Six of them presented with pain mimicking toothache, temporomandibular joint disorders or trigeminal neuralgia, while two showed osteopenic bone lesions in the panoramic radiography, and perimandibular swelling. Anesthesia of the lower lip was the only common clinical feature. In seven of the eight patients, a whole body bone scintigraphy and single photon emission computed tomography (SPECT) of the skull in combination with a whole body and SPECT anti-granulocyte (Tc-99m MAK 250/183) bone marrow scintigraphy was performed. One patient did not have combined scintigraphy performed secondary to severe systemic illness. In six of the seven, the results were conclusive for a metastatic bone lesion. Biopsies confirmed three patients to have a previously unrecognized primary cancer, one patient to have previously unrecognized recurrent cancer, and three patients to exhibit new metastatic spread of an already diagnosed cancer. Histology revealed breast, lung, renal cancer and a malignancy of inconclusive origin. In the remaining patient, combined scintigraphy suggested osteomyelitis, yet biopsy revealed a prostate cancer metastasis with acute inflammatory cell infiltration. Thus, the scintigraphy pattern of a hot spot in the bone scan and a cold lesion in the bone marrow scintigraphy is highly suggestive of a mandibular metastasis, if accompanied by anesthesia of the lower lip.

Pattern recognition in five-phase bone scintigraphy: diagnostic patterns of reflex sympathetic dystrophy in adults

The objective of this study was to assess qualitative and quantitative patterns of tracer accumulation to increase the diagnostic utility of bone scintigraphy in reflex sympathetic dystrophy (RSD). Of 120 patients with high clinical suspicion for RSD, 96 were confirmed as having RSD during follow-up, while the remaining 24 were used as controls. Clinical parameters were measured and correlated to five activity ratios (0–30 s, 0.5–5 min, 5–15 min, 3 h, 24 h) and five scintigraphic signs. Monitoring three dynamic phases revealed different tracer kinetics of potential diagnostic utility; however, the 24-h bone phase offered no additional diagnostic contribution and can be omitted. Quantification provided objective parameters for the duration of symptoms, pain and impairment of movement but not for surface temperature differences, swelling and impairment of physical force. It is of limited use for diagnosis except for the exclusion of disease. Discriminant analysis revealed the combination of three signs (diffuse uptake in carpus/tarsus+diffuse uptake in all small joints+increased activity ratio in the late blood pool phase) to be the pattern with the highest diagnostic accuracy independent of localisation, sex, age and precipitating factors. It is concluded that the scintigraphic confirmation of RSD is based on lateralisation in the late blood pool phase and the described pattern in the early bone phase.

Concomitant hyperparathyroidism and nonmedullary thyroid cancer, with a review of the literature.

Purpose Primary hyperparathyroidism and concomitant thyroid cancer is a rare and complicated setting for diagnostic imaging. Materials and Methods The authors report the accidental finding of primary hyperparathyroidism in a patient with rapid enlargement of a thyroid nodule and the results of a literature review. Results Tl-201–Tc-99m subtraction scintigraphy correctly revealed the malignant nature of a large cold thyroid nodule and mediastinal parathyroid hyperplasia. In contrast, high-resolution ultrasound indicated a retrothyroidal hyperplastic parathyroid gland. Surgery followed the findings of the preoperative ultrasound and intraoperative biopsy, yet hyperparathyroid disease persisted. Repeated scintigraphy confirmed an ectopic parathyroid gland, which was resected from a paraesophageal location. Subsequently, hormone and calcium levels returned to normal and remained normal during a follow-up period of 3 years. A literature review revealed a prevalence of approximately 3% of nonmedullary thyroid cancer, which was found in patients operated on for primary hyperparathyroidism. Previous neck irradiation, especially in childhood, appears to be a risk factor for the development of both nonmedullary thyroid carcinoma and for primary hyperparathyroid disease. Conclusions This case illustrates the need for clinical awareness of concomitant hyperparathyroidism and nonmedullary thyroid cancer and is substantiated with published case reviews. The preoperative scintigraphic localization of hyperfunctioning parathyroid tissue, although not advised as a routine procedure, may provide diagnostic information in addition to high-resolution ultrasound and intraoperative biopsy. In addition, scintigraphy can be useful even in the technically difficult setting of concomitant thyroid cancer.

Does 99mTc-Sestamibi in High-Grade Malignant Brain Tumors Reflect Blood–Brain Barrier Damage Only?

(99m)Tc-Sestamibi (MIBI) has been successfully applied in recurrent glioblastoma. The aim of this study was to evaluate the incremental diagnostic information of MIBI as a tumor-avid radiopharmaceutical compared with (99m)Tc-pertechnetate ((99m)Tc) as sole indicator of the integrity of the blood-brain barrier. Twenty-five patients with confirmed recurrent brain tumors were included. MIBI SPET was performed 10 min after injection of 555 MBq MIBI intravenously with a triple-headed gamma camera equipped with LE-UHR-PAR collimators over 360 degrees (3 degrees /step) and stored in a 128(2) matrix. Identical acquisition parameters were used for (99m)Tc SPET, which was acquired 3 h after injection of 740 MBq (99m)Tc. Normalized tumor uptake (NU) was calculated from attenuation-corrected transaxial slices. In addition, tumor/plexus, tumor/nasopharynx, and tumor/parotid gland ratios were assessed in both studies. No statistically significant differences were detected for the mean NU of tumor tissue with MIBI (0.26 +/- 0.10) and (99m)Tc (0.39 +/- 0. 33) and for the tumor/nasopharynx and tumor/parotid gland ratios; only the tumor/plexus ratio was significantly higher for (99m)Tc than for MIBI (p < 0.05). In conclusion, our data indicate that MIBI scintigraphy in brain tumors at 10 min postinjection reveals no additional visual information over that provided by the conventional (99m)Tc-pertechnetate brain scan, and in addition, tracer retention reflects primarily blood-brain barrier damage.

Three-phase bone scintigraphy of hydroxyapatite ocular implants

Hydroxyapatite ocular implants are replicas of lamellar bone tissue derived from the exoskeleton of a reef-building coral by a hydrothermal chemical exchange reaction. Attached to the eye muscles, they act as a passive framework for fibrovascular ingrowth and can be drilled to hold the visible part of the artificial eye and allow synchronous eye movement. Fibrovascular ingrowth has to be confirmed by bone scintigraphy before the drilling procedure. This study monitored the vascular ingrowth into the implant in ten patients over 12 months to establish a clinically feasible imaging protocol. Tracer accumulation was monitored visually and quantitatively in dynamic and single-photon emission tomography (SPET) scans after the intravenous administration of 600 MBq of99mTc-DPD. The implants showed no tracer accumulation in the arterial or blood pool phase. Accordingly, dynamic scintigraphy can be omitted from the imaging protocol. Delayed tracer accumulation appeared no earlier than 2 and no later than 6 months after surgery. Planar scintigraphy is not recommended as high-resolution SPET is necessary to separate the implant from the surrounding bone. We conclude that imaging can be confined to high-resolution SPET 3 h after tracer injection, no earlier than 3 months after surgery. The vascularized hydroxyapatite orbital implant is an important in vivo model for bone-seeking agents to study their uptake kinetics independently of any soft tissue and bone disease. Our results provide evidence that in normal bones the chemical adsorption of99mTc-DPD into the crystalline structure of hydroxyapatite is the only quantitatively relevant uptake mechanism.

Is early sestamibi imaging in head and neck cancer affected by MDR status, p53 expression, or cell proliferation?

A consensus has emerged that early imaging (within 20 min post-injection [p.i.] of sestamibi) has the highest diagnostic yield. Tc-99m-sestamibi uptake has been associated with P-glycoprotein-mediated multi-drug resistance (MDR), tumor vascularization, invasiveness, and cell proliferation. The aim of this study was to assess whether these parameters affect tumor uptake in current imaging protocols. Twenty-three patients with squamous cell carcinoma (SCC) of the mouth floor who were scheduled for surgery were imaged 5 min. p.i. with a triple-head gamma camera (360 degrees, 3 degrees/step SPECT, UHRPAR collimators). Tumor:nontumor tissue (TBR), tumor:gingiva (TGR), tumor:salivary gland (TSR), and tumor:nuchal muscle ratios (TNR) were calculated based on the cts/pix values of ROIs in the axial slices. The expression of the MDR gene was determined histochemically from biopsies. Cell proliferation was quantitated by the histochemical analysis of the Ki-67 protein (Ki-67 index); additionally, the p53 tumor suppressor gene (p53 index), a posttranslational stabilizer of the cell cycle at the G1 stage, was assessed. No significant differences were found for the uptake indices between MDR+ and MDR- tumors. Moreover, no significant correlation between sestamibi uptake and the Ki-67 and p53 indices could be demonstrated. The diagnostic information content of currently applied imaging protocols for sestamibi in SCC of the mouth floor is not affected by tumor-specific properties.

Technetium-99m labelled LDL as a tracer for quantitative LDL scintigraphy

The goal of the present study was to optimize technetium-99m labelling of low-density lipoprotein (LDL) and to investigate the in vitro and in vivo properties of the tracer to determine whether its application for quantitative scintigraphy of hepatic LDL receptor activity is feasible. LDL labelled with iodine-125 by the iodine monochloride method was used as a reference tracer. Comparison of different assessments of radiochemical purity [trichloro-acetic acid precipitation (%ppTCA), paper chromatography, size-exclusion chromatography and chloroform-methanol extraction] exhibited %ppTCA to be superior as a parameter of tracer quality. In spite of a high radiochemical purity immediately after labelling, modifications of 99mTc labelling of LDL did not overcome the poor long-term stability of the tracer. Subsequent dialysis in phosphate buffer over about 3 h sufficiently increased the long-term stability in vitro and in vivo. The competitive recognition of dialysed 99mTc-LDL and 125I-LDL with native LDL by high-affinity binding sites was demonstrated in human hepatoma cells (HepG2) and human fibroblasts. Biodistribution data of simultaneously injected 99mTc-LDL and 125I-LDL in New Zealand White rabbits showed a high uptake of both tracers in tissues with high LDL receptor activity, yet 99mTc-LDL uptake exceeded 125I-LDL uptake by two- to sevenfold. In contrast to 125I-LDL, 99mTc-LDL showed a higher unspecific uptake into the bone marrow and the spleen, suggesting an additional uptake mechanism probably via the scavenger pathway. Curve deconvolution of plasma clearance in five female New Zealand White rabbits and five male hyperlipidaemic patients again showed a marginally different biokinetic behaviour of 99mTc-LDL and 125I-LDL. It is concluded that dialysis of 99mTc-LDL substantially increases long-term stability, which is essential for quantification purposes, and that the dialysed tracer has retained its biological integrity as it is recognized by the LDL receptor in vitro. It remains to be determined to what extent the estimation of hepatic LDL receptor activity by quantitative 99mTc-LDL scintigraphy is influenced by the different biokinetic behaviour of 99mTc-LDL and 125I-LDL.

Does Dyspnoea during dipyridamole cardiac stress testing indicate bronchospasm and is the pretest clinical history predictive of this side-effect?

This study investigates the acute effects of intravenous dipyridamole (0.7 mg/kg) on pulmonary airflow in relation to clinical paramaters suggestive of chronic obstructive pulmonary disease (COPD) in order to assess predictive and causative factors of dyspnoea during cardiac stress testing. Mild pulmonary airflow obstruction was noted in all patients, but reached statistical significance only in small airways (FEF75–85%: −7%;P=0.034). The changes in pulmonary function parameters were independent of the clinical history. Dyspnoea under dipyridamole stress testing occurred in parallel with angina, yet was not associated with ischaemic or non-ischaemic left ventricular dysfunction. These data do not support the use of dipyridamole stress testing in asthmatics, but show that (1) the acute effects of a diagnostic dose of dipyridamole on pulmonary airflow are mild even in patients with a history suggestive of COPD and (2) dyspnoea during dipyridamole testing is not necessarily indicative of bronchospasm.