Metastatic squamous carcinoma in the neck: an anatomical and physiological study using CT and SPECT 99Tcm (V) DMSA.

Technetium-99m (99Tcm) (V) dimercaptosuccinic acid (DMSA) is a new tumour imaging agent that has been used to image squamous cell carcinoma (SCC) of the head and neck. This study has been undertaken to compare clinical examination with computed tomography (CT) (anatomical) and SPECT 99Tcm (V) DMSA (physiological) imaging in the evaluation of metastatic SCC of the neck. Twenty-five patients with head and neck cancer were studied. Computed tomography was as sensitive but more accurate than clinical examination in predicting the presence of cancer. SPECT 99Tcm (V) DMSA was inferior to both techniques in identifying metastatic disease. There is no role for SPECT 99Tcm (V) DMSA imaging in the management of patients with SCC metastatic to the neck. Combined imaging with CT offered no advantages over anatomical imaging with CT alone. There is no role for CT in the routine evaluation of the clinically N0 neck and the role of CT of the neck in the management of patients with metastatic SCC is discussed.     

99Tcm (v) DMSA and 67Ga-citrate imaging in patients with head and neck squamous carcinoma: a clinical and scintigraphic study

Technetium-99m (99Tcm) (v) dimercaptosuccinic acid (DMSA) is a new tumour imaging agent which has been used to image medullary carcinoma of the thyroid and squamous cell carcinoma (SCC) of the head and neck. This study was undertaken to compare planar scintigraphy in patients with head and neck SCC using 99Tcm (v) DMSA and the established tumour imaging agent gallium-67 citrate (67Ga). Seventeen patients were studied of whom 16 had a head and neck malignancy. Clinical examination was more sensitive and accurate than 67Ga scintigraphy, which in turn was more sensitive and accurate than 99Tcm (v) DMSA in detecting patients with cancer, patients with primary tumours and patients with metastatic neck carcinoma. Neither 67Ga or 99Tcm (v) DMSA planar scintigraphy has any role to play in the routine evaluation at presentation of patients with head and neck SCC.     

Pharmacokinetics, biodistribution and dosimetry of 99Tcm(V)DMSA in humans with squamous cell carcinoma

Technetium-99m (99Tcm)(V) dimercaptosuccinic acid (DMSA) is a new tumour imaging agent which has been used to evaluate squamous carcinoma (SCC) of the head and neck. This study evaluated the pharmacokinetics and biodistribution of 99Tcm(V)DMSA in patients with SCC and calculated the bone mass of a New Zealand White (NZW) rabbit. This data was then used to calculate the effective dose equivalent in man. A total of 16 patients were studied (5 with no tumour, 11 with tumour). 99Tcm(V)DMSA had a fast bi-exponential blood clearance in patients with no tumour (30 and 401 min) and patients with tumour (30 and 387 min) with no significant difference (p greater than 0.05) between the two groups. 99Tcm(V)DMSA had a fast cumulative urine excretion with mean half-times in non-tumour and tumour patients of 183 min and 244 min respectively. There was no significant difference (p greater than 0.05) between these two latter groups. The effective dose equivalent of 99Tcm(V)DMSA in man is 5.1 microSv/MBq.     

99Tcm (v) DMSA: a clinical, planar and SPECT study to evaluate patients with head and neck squamous carcinoma

Technetium-99m (99Tcm) (v) dimercaptosuccinic acid (DMSA) is a new tumour imaging agent which has been used to image squamous cell carcinoma (SCC) of the head and neck. This study was undertaken to compare planar versus SPECT 99Tcm (v) DMSA scintigraphy in patients with head and neck SCC. Thirty-four patients were studied. Twenty-eight had SCC, and of these, four had received previous treatment with surgery or irradiation. SPECT was as sensitive and as accurate as clinical examination (but more sensitive and accurate than planar scintigraphy) in detecting which patients had cancer and which patients had primary tumours. SPECT was more sensitive and more accurate than planar scintigraphy (but less sensitive and accurate than clinical examination) in detecting lateral neck compartments with metastatic carcinoma. SPECT correctly upstaged 6% of clinically N0 necks. Although SPECT 99Tcm (v) DMSA scintigraphy improved the image quality, sensitivity and spatial resolution of the investigation, it has no role to play in the routine evaluation of patients with head and neck SCC (to include the clinically N0 neck).     

99Tcm (v) DMSA: the pituitary sign

Technetium-99m (99Tcm) (v) dimercaptosuccinic acid (DMSA) is a new tumour imaging agent which has been used to evaluate head and neck tumours. It has a normal head and neck biodistribution to include the lacrimal glands, nasal mucosa and the blood-pool. Seventy-seven patients were studied of whom 63 had a head and neck malignancy. Of these patients, 19 (25%) exhibited positive accumulation of radioactivity in the region of the pituitary gland and this was a constant finding in those followed-up after treatment. Biodistribution studies in forty New Zealand white rabbits confirmed pituitary accumulation of 99Tcm (v) DMSA. The pituitary gland region should be included in the normal biodistribution of 99Tcm (v) DMSA.     

99Tcm(v)-DMSA planar scintigraphy: does it have a role in the management of patients with head and neck squamous carcinoma?

99Tcm(v)-DMSA is a new tumour-imaging agent which has recently been proposed as a scintigraphic marker for head and neck squamous cell carcinoma (SCC). Seventy-seven patients were studied prospectively, of whom 58 had a history and diagnosis of head and neck SCC. All patients were examined, imaged using 99Tcm(v)-DMSA planar scintigraphy and then followed up clinically. In addition, 35 patients were followed up with scintigraphy (81 studies). Scintigraphy was less sensitive and less accurate than clinical examination for the overall detection of patients with SCC, for the detection of patients with SCC at presentation and for the detection of patients with primary tumours, possible nodal disease and with residual and recurrent disease following surgery and irradiation. Approximately 50% of patients exhibited positive uptake of 99Tcm(v)-DMSA in the salivary glands following radiotherapy. Although 99Tcm(v)-DMSA is accumulated at sites of head and neck SCC, its inability to detect low volume disease and apparent low specificity following surgery and irradiation means it has no role to play in the routine evaluation of patients with head and neck SCC.     

The role of technetium-99m pentavalent DMSA in the management of patients with medullary carcinoma of the thyroid

In order to assess the role of 99Tcm pentavalent dimercaptosuccinic acid (99Tcm (V)DMSA) scanning in the management of patients with medullary carcinoma of the thyroid, we imaged 10 patients with histologically proven disease. Nine of the 10 patients were scanned after removal of the primary tumour, but with symptomatic or biochemical evidence of recurrence. One patient was imaged prior to thyroidectomy. In eight of the 10 patients 99Tcm(V)DMSA successfully identified tumour deposits, and it has been shown in this study to be a cheap, convenient radiopharmaceutical for studying this group of patients, producing high-quality images with low radiation doses, and contributing significantly to patient management.     

Imaging of head and neck tumors with technetium(V)-99m DMSA. A new tumor-seeking agent

Tumor scintigraphy, using Tc(V)-99m DMSA was performed on 76 patients with head and neck tumors. In 32 cases, SPECT also was performed. Tc(V)-99m DMSA was found to have a sensitivity of 75% (56 cases), a specificity of 85% (20 cases) and an accuracy of 78% on planar imaging. ECT studies showed accumulation of Tc(V)-99m DMSA in all 25 malignant cases studied. However, in benign tumors, four of seven cases (57%) showed radionuclide uptake. Tc(V)-99m DMSA has superior physical properties to Ga-67 and could be of use in the diagnosis of head and neck tumors.     

Localization and stability of technetium-99m-Sn-pyrophosphate in rat neutrophils

Technetium-99m has been suggested as an alternative radiolabel for white cells, and while its physical characteristics are nearly ideal, its stability and site of localization in this procedure are unclear. We examined these parameters by radiolabeling 10(8) neutrophils from rat peritoneum with 74 to 370 MBq technetium-99m-Sn-pyrophosphate. We found that the percentage of initial activity bound to neutrophils was quite variable, possibly because the radiolabel associated with several subfractions: 19.8 +/- 11.5% (mean +/- s.d.) with nuclei and plasma membranes, 25.6 +/- 3.9% with mitochondria, 26.6 +/- 9.8% with microsomes, and 29.2 +/- 6.9% with cytosol. Approximately 80-90% of the radioactivity associated with neutrophils was not bound to protein and only about one-half of the activity localized to cell membranes was removable over 4 hr by pepsin digestion. We concluded that the variable labeling efficiency was due to the radiolabel's rather loose association with several cellular subfractions rather than specific binding to a unique substrate.     

What is the optimal imaging time for 99Tcm-(V)-DMSA planar scintigraphy in the detection of squamous carcinoma? A comparative study in humans and in an animal tumour model

99Tcm-(V)-DMSA is a new tumour imaging agent which has been used to image squamous cell carcinoma (SCC) of the head and neck. There have been, however, no studies to date evaluating its optimal imaging time for SCC. Seven patients were studied (six SCC; one nontumour) and seven rabbits (six with SCC, (17 tumours); one nontumour). For the human qualitative studies there was a 67% sensitivity at 2, 4 and 6 h with image quality being optimum at 4 h. Maximum quantitative uptake occurred between 2 and 4 h. For the rabbit qualitative studies the optimum imaging time was 4 h (92% sensitivity, 100% specificity) and maximum quantitative uptake occurred at between 1.5 and 5 h. Taking into account the human and rabbit qualitative and quantitative studies combined with the pharmacokinetics and biodistribution of 99Tcm-(V)-DMSA, the optimum imaging time of 99Tcm-(V)-DMSA in humans with SCC was between 2 and 4 h.     

Determination of medullary thyroid carcinoma metastases by 201Tl, 99Tcm(V)DMSA, 99Tcm-MIBI and 99Tcm-tetrofosmin.

Medullary carcinoma of the thyroid (MCT) is malignancy derived from the parafollicular cells (or C-cells) of the thyroid. It is usually sporadic, although it is familial in some cases. Several scintigraphic procedures can provide information regarding the primary and metastatic foci of the tumour. We performed whole-body scanning to establish the pathology of MCT using 201Tl, 99Tcm(V)DMSA and 99Tcm-MIBI in 14 patients, and found average sensitivities of 73%, 82% and 81%, respectively. Moreover, we also scanned three patients with 99Tcm-tetrofosmin and identified two of four pathological foci as well as residual thyroid tissue. The sensitivities of 201Tl, 99Tcm(V)DMSA and 99Tcm-MIBI were 100%, 100% and 85% in identifying lymphadenopathies; 40%, 50% and 71% for soft tissue foci; 100% and 100% for foci in pulmonary parenchyma; and 100%, 66% and 100% for recurrences in thyroid gland. Although 99Tcm(V)DMSA identified all bony metastases in three patients (100%), 99Tcm-MIBI detected only two of three foci (66%) and 201Tl none. 201Tl, 99Tcm-MIBI and 99Tcm-tetrofosmin accumulated in residual thyroid tissue, but 99Tcm(V)DMSA did not, as expected. We conclude that these agents were complementary, since they had different sensitivities in different tissues. The tumour-seeking properties of tetrofosmin are to be evaluated in a larger series.     

Technetium-99m (v) dimercaptosuccinic acid uptake in patients with head and neck squamous carcinoma: experience in imaging

A recently developed imaging agent, technetium-99m (v) dimercaptosuccinic acid (99mTc (v) DMSA), has been used to assess head and neck squamous carcinoma (SCC). We have prospectively studied 62 patients of whom 53 had a histologically proven head and neck SCC. The remaining nine had benign lesions. The results of planar imaging in patients with primary disease yielded an 85% sensitivity and 78% specificity. Planar imaging in patients with cervical lymphadenopathy revealed a 59% sensitivity. Nineteen patients also had single photon emission computed tomography imaging which improved the image quality, spatial resolution and sensitivity of the investigation. Twenty-seven patients were scanned before and after radiotherapy and, of these, 96% showed positive uptake in the salivary glands with no evidence of tumor recurrence. This study has shown 99mTc (v) DMSA imaging provides a cheap and rapid method of investigating head and neck SCC and further studies are necessary to evaluate its role in the management of patients with this disease.     

Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate. II. Subcellular localization of 99Tc-DMS complex in the rat kidney in vivo

In order to extend and confirm our previous studies of in vivo behaviour of 99mTc-DMS in rat kidney cells, the intracellular localization of 99Tc-DMS complex in rat kidney tissue was examined. Animals were injected IV with 99Tc-DMS solution (37 kbq in 1.0 ml) 2 h before killing. Dissected kidneys were homogenized and submitted to differential centrifugation to obtain organelles. The following radioactivity distribution in relation to the total radioactivity of homogenate was obtained in nine experiments: nuclei 3.30% (+/-1.27), mitochondria 9.48% (+/-2.17), microsomes 7.03% (+/-2.34) and cytosol 57.45% (+/-8.01). The subcellular distribution pattern of 99Tc-DMS was in very good agreement with the pattern of 99Tc-DMS binding to kidney cell organelles obtained by the same procedure. Soluble cytoplasmic proteins binding 99Tc-DMS were excluded from a Sephadex G-25 column with the void volume. Their electrophoretic mobility after agarose gel electrophoresis corresponded to beta-lc- and alpha-2-macroglobulins. The results obtained show unambiguously that the investigated complex penetrates into the kidney cells where it binds mostly to soluble cytoplasmic proteins and mitochondria, and to a lesser extent to both microsomes and nuclei. In another series of six experiments, isolated kidney cortical tissue was used, the same procedure was repeated and similar results were obtained.     

99Tcm-diastereomeric dimercaptosuccinic acid complexes: comparison of their biodistribution

The biodistribution of two stereoisomeric 99Tcm complexes derived from diastereomeric dimercaptosuccinic acids (DMSA), 99Tcm-dl-DMSA and 99Tcm-meso-DMSA, was examined in sarcoma 180 tumour-bearing mice. The biodistribution pattern of meso-complex was not significantly different from 99Tc(V)m-DMSA, a new tumour imaging agent, while the dl-complex did not show the osteotropic property observed in meso- and 99Tc(V)m-DMSA complexes. The ratio of tumour to blood was superior for the 99Tcm-dl-DMSA (2.68) over the 99Tcm-meso-DMSA (1.25) at 3 h, and the ratio was reversed at 6 h, 3.13 to 4.28. The results indicate that dl-complex is of importance for the possible use in tumour imaging.     

Oxygen bubbling can improve the labelling of pentavalent technetium-99m dimercaptosuccinic acid

It has previously been reported that almost all of the trivalent technetium-99m dimercaptosuccinic acid (^99mTc (III) DMSA) present in the labelling product of pentavalent technetium-99m DMSA (^99mTc (V) DMSA) can be changed into^99mTc (V) DMSA by bubbling with pure oxygen. We therefore performed studies in animals (mice) and humans to investigate the effect of such oxygen bubbling on the labelling efficiency of and on the renal uptake of^99mTc. The method of labelling of^99mTc (V) DMSA was that of Hirano. It was found that oxygen bubbling oxidized the contaminated^99mTc (III) DMSA into^99mTc (V) DMSA in vitro and decreased the uptake of radioactivity in the kidney in both animals and humans.     

Comparison of 99Tcm dimercaptosuccinic acid scans and intravenous urography in children

A retrospective comparison of 99Tcm dimercaptosuccinic acid (DMSA) scans and intravenous urograms (IVUs) was performed on a large, unselected paediatric population to assess critically the relative merits of these two techniques. A total of 205 children were studied, providing 388 kidneys for comparison. The studies agreed in 81%, both being normal in 39%, and both abnormal in 42%. In 28 kidneys (7%), the IVU was abnormal when the 99Tcm DMSA was normal. There was a collecting system abnormality in 27 kidneys, but 10 kidneys also showed a parenchymal abnormality. In all these the parenchymal abnormality was global thinning on the IVU, and the contralateral kidney was small. In 40 kidneys (10%) the 99Tcm DMSA was abnormal when the IVU was normal: the abnormalities demonstrated were predominantly focal defects. After excluding IVUs of poor diagnostic quality, only 14 kidneys (3.6%) showed this disparity. The important clinical subgroups are infection, with or without reflux (27 kidneys), hypertension (4) and neonates with poor renal function (2). The one false positive 99Tcm DMSA was a result of an anatomical variant. Global thinning in a "normal" kidney on a 99Tcm DMSA scan may be overlooked when the contralateral kidney is poorly functioning and small.     

Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate

Rat kidney tissue homogenates, incubated in vitro with ⁹⁹Tc-DMS were subjected to differential centrifugation. Specific radioactivities of subcellular fractions were as follows: cytosol 13,552, microsomes 3,600, mitochondria 2,707 cpm/mg protein, and nuclei 2,642 cpm/mg DNA.The cytosol fraction was further analyzed by ion-exchange chromatography on DEAE-Sephadex A-25 column. In this way it was separated into several distinct protein zones, three of them bearing a significant amount of ⁹⁹Tc-DMS preparation. The highest specific radioactivities of proteins were eluted from the DEAE-Sephadex column with 30 mmol/l and 50–110 mmol/l NaCl solution.Total nucleic acids isolated from purified nuclei, mitochondria and microsomes contained a certain amount of bound ⁹⁹Tc-DMS complex. Nuclear nucleic acids had the highest specific radioactivity, suggesting that ⁹⁹Tc-DMS complex penetrates into the nuclei.     

Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate

Subcellular distribution of ^99mTc-DMS (dimercaptosuccinic acid) complex in the rat kidney has been studied. One hour after IV injection of labelled DMS preparation kidney tissue homogenate was subjected to differential subfractionation to obtain cell organelles. Radioactivity distribution in relation to total radioactivity of kidney homogenate obtained in five repeated experiments was as follows (±SD): nuclei 4.56% (±0.7); mitochondria 5.97% (±0.7); microsomes 3.63% (±0.8) and cytosol 30.92% (±1.8). Specific activities expressed as counts/min/mg of protein were 148,520 (±15%), 97,440 (±17.7%) and 76,180 (±29%) for mitochondria, cytosol and microsomes respectively. Specific activity of the nuclei was 230.060 (±27%) counts/min/mg of DNA. These results show without doubt that this renal imaging agent, successfully used in human medicine, penetrates into the kidney cells where it binds mostly to soluble cytoplasmic proteins and mitochondria and, to a lesser extent, to both microsomes and nuclei.     

Binding of 99Tcm sulphur colloid to blood components: implications in renal transplant rejection

The percentage binding of 99Tcm sulphur colloid to blood components (formed elements and plasma proteins) was studied within 1 min of the intravenous injection of the radiopharmaceutical in humans as well as rats. In humans, 68% of the total blood counts were bound to the formed elements (erythrocytes, leucocytes and platelets). The binding pattern (as percentage of plasma counts) among the plasma protein fractions in humans was as follows: albumin, 9.85 +/- 2.06; fibrinogen, 56.70 +/- 7.96; and total proteins, 66.55 +/- 7.32. Activity bound to fibrinogen represented 82.3 +/- 9.1% of the total protein-bound activity in humans. In rats as well fibrinogen was the predominant binding protein (73.8 +/- 5.6). The significant binding of the 99Tcm sulphur colloid to plasma fibrinogen and formed elements of blood may be one of the reasons for the uptake of this radiocolloid in renal transplants before rejection.     

99mTc(V)DMSA quantitatively predicts 188Re(V)DMSA distribution in patients with prostate cancer metastatic to bone

Rhenium-188 dimercaptosuccinic acid complex [188Re(V)DMSA], a potential therapeutic analogue of the tumour imaging agent 99mTc(V)DMSA, is selectively taken up in bone metastases in patients with prostate cancer. It would be helpful in planning palliative radionuclide therapy if 99mTc(V)DMSA could be used to predict tumour and kidney retention of 188Re(V)DMSA. The aim of this study was to determine the correlation between tumour-to-normal tissue ratios and kidney-to-soft tissue ratios of 99mTc(V)DMSA and 188Re(V)DMSA. This would determine whether a scan with 99mTc(V) DMSA could be used to identify patients for whom 188Re(V)DMSA treatment would be contra-indicated, and enable prediction of relative kidney and tumour radiation absorbed dose in 188Re(V)DMSA treatment. Ten patients with prostate carcinoma were recruited following observation of disseminated bone metastases on a recent 99mTc-hydroxydiphosphonate bone scan. Whole-body planar scans were obtained at ca. 4 h and 24 h after hydration and injection of 600 MBq 99mTc(V)DMSA, and a week later, at similar times after hydration and injection of 370 MBq 188Re(V)DMSA. A triple-energy window (TEW) scatter correction was applied to the 188Re scans. Counts per pixel were determined in regions of interest drawn over metastatic sites, kidneys and normal soft tissue. Tumour-to-soft tissue ratios were significantly lower (by a factor of approximately 0.8 after the TEW was applied) on 188Re scans than on 99mTc scans, but the two were highly linearly correlated both in all individual patients and in tumours pooled from all patients together both at 4 h and at 24 h. Kidney-to-soft tissue ratios were similarly correlated and were lower for 188Re than for 99mTc by a similar factor. Both tumour- and kidney-to-soft tissue ratios increased between 4 and 24 h but the latter increased more. In conclusion, only minor differences were seen between 99mTc and 188Re scans, and kidney-to-background ratios on 188Re scans were not higher than on 99mTc scans. These differences are insufficient to infer that they are due to a real difference in biodistribution, and they may be due only to different physical imaging characteristics. Thus 99mTc(V)DMSA scans are predictive of 188Re(V)DMSA biodistribution and could be used to estimate tumour and renal dosimetry and assess suitability of patients for 188Re(V)DMSA treatment.