In vitro and in vivo studies with pentavalent technetium-99m dimercaptosuccinic acid

The purpose of this investigation was to characterise the in vivo chemistry and binding mechanisms of technetium-99m dimercaptosuccinic acid [^99mTc(V)DMSA]. Biodistribution was studied in mice by frozen section whole-body autoradiography and microautoradiography in selected tissues. Binding to bone mineral analogues was studied in vitro using various forms of calcium phosphate and hydroxyapatite under varied conditions. Similar studies with^99mTc-hydroxymethylene diphosphonate (HDP) were also carried out for comparison. The in vivo stability of^99mTc(V)DMSA was monitored by high-performance liquid chromatographic analysis of blood and urine samples taken over 24 h from patients injected with the tracer. Whole-body autoradiography shows that^99mTc(V)DMSA has highest affinity for bone (cortical rather than medullary) in mice. Substantial uptake of the tracer was also observed in the kidney (cytoplasm of cortical renal tubular cells). No specific localisation was observed in the liver at either the microscopic or the macroscopic level. While^99mTc-HDP bound strongly to calcium phosphates under all conditions,^99mTc(V)DMSA binding was inhibited in the presence of phosphate and was stronger at pH 6.0 than at pH 7.4. In non-phosphate buffers, however, the binding of^99mTc(V)DMSA remained high across the pH range 4–7.4.^99mTc(V)DTVISA binds to calcium phosphates chemically unaltered, and no radioactive species other than the three isomers of^99mTc(V)DMSA were detected in blood or urine samples taken from patients up to 24 h after injection.^99mTc(V)DMSA is stable in vivo, and no conversion of the complex to other chemical species needs to be invoked to explain its uptake in bone metastases or soft tissue tumour. Bone affinity may be due to reversible binding of the unaltered complex to the mineral phase of bone.     

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.     

99mTc-human immunoglobulin (HIG) — first results of a new agent for the localization of infection and inflammation

Technetium (^99mTc) labelled, polyclonal human immunoglobulin (HIG) is a new agent that detects focal infection and inflammation. This new agent was compared in 40 patients with the accepted standard, namely¹¹¹In-oxine-labelled leucocytes. This comparison resulted in a sensitivity of 94% and a specificity of 96% for^99mTc-HIG when¹¹¹In-oxine leucocytes were defined as giving the true result. The new agent was shown to localize both sepsis and active inflammatory bowel disease (IBD). There was 100% concordance in the 16 patients with IBD who were imaged with both^99mTc-HIG and¹¹¹In-oxine leucocytes. Discordant results were obtained in one case of suspected osteomyelitis, which was false-positive on the^99mTc-HIG scan, and one case of pyrexia of unkown origin when the^99mTc-HIG was false-negative and the¹¹¹In-oxine leucocyte scan demonstrated accumulation of tracer in the caecum at 24 h post-injection. Normal distribution for^99mTc-HIG demonstrated activity in the kidneys and bladder and that 50% of the tracer is cleared through the kidneys during the first 24 h post-injection. There were no major or minor side-effects.     

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.     

Tc-citrate versus Ga-citrate for the scintigraphic visualization of inflammatory lesions

Citric acid was labeled with ^99mTc with an efficiency of > 99%. The biodistribution of ^99mTc-citrate was studied in mice with turpentine-induced abscesses in comparison to ⁶⁷Ga-citrate. The max. concentration ratios were 4.61 ± 1.92 (3 h) for ^99mTc-citrate and 4.76 ± 2.04 (4h) for ⁶⁷Ga-citrate. Arthritis was induced in 10 rabbits by intra-articular injection of ovalbumin Scintigrams obtained 4 days later and at 3 h post-injection of ^99mTc-citrate showed increased activity involving the synovium. The max. knee ratio was 3.19 ± 1.29 (3 h) and 6.47 ± 3.71 (24 h) for ^99mTc- and ⁶⁷Ga-citrate, respectively. The blood clearance curve of ^99mTc-citrate in rabbits was biexponential with a fast ( ) and a slow ( ) component, compared to mono-exponential clearance of ⁶⁷Ga-citrate ( ). In 10 patients with rheumatoid arthritis whole-body scintigrams and spot images of involved joints indicated localization of the tracer in inflamed tissues. The mean target-to-soft tissue ratios were 3.04 ± 0.81 and 4.95 ± 2.56 for ^99mTc-citrate and ^99mTc-MDP, respectively. Renal clearance of radioactivity was evident from the scintigrams. Our results demonstrated that ^99mTc-citrate is effective as a radiopharmaceutical for the visualization of inflammatory lesions and may be preferred to ⁶⁷Ga-citrate due to the ideal physical characteristics of the radionuclide, easy preparation, low cost, early accumulation and the preference for the renal route of excretion.     

Scintigraphic detection of recurrence of medullary thyroid cancer

A case of recurrent medullary thyroid cancer (MTC) was evaluated with¹²³I-MIBG,^99mTc(V)-dimercaptosuccinic acid (DMSA), and²⁰¹Tl scintigraphy. This patient had been operated on for MTC in the right thyroid. Recently a left neck mass was noticed, and was suspected of being a. recurrence of MTC based on increased plasma calcitonin (CT) and carcinoembryonic antigen (CEA). He was operated on for the neck mass which revealed MTC, and papillary thyroid cancer was incidentally found in the left thyroid, but the CT and CEA levels remained high, and remaining MTC tumor was suspected. But the location of the tumor was unknown. Although^99mTc(V)-DMSA scintigraphy is generally believed to be superior in sensitivity to¹²³I-MIBG scintigraphy, it did not demonstrate the tumor site but²⁰¹Tl and¹²³I-MIBG did. Furthermore,¹²³I-MEBG scintigraphy has greater specificity for tumors which arise in the neural crest. Judging from the results of this case and cases reported in the literatures, both¹²³I-MIBG and^99mTc(V)-DMSA should be performed in the detection of recurrent MTC.     

Pentavalent rhenium-188 dimercaptosuccinic acid for targeted radiotherapy: synthesis and preliminary animal and human studies

Pentavalent rhenium-188 dimercaptosuccinic acid [¹⁸⁸Re(V)DMSA] is a β-emitting analogue of ^99mTc(V)DMSA, a tracer that is taken up in a variety of tumours and bone metastases. The aim of this study was to develop the kit-based synthesis of the agent on a therapeutic scale, to assess its stability in vivo, and to obtain preliminary biodistribution and dosimetry estimates, prior to evaluation of its potential as a targeted radiotherapy agent. The organ distribution of ¹⁸⁸Re in mice was determined 2 h after injection of 3 MBq ¹⁸⁸Re(V)DMSA prepared from eluate from a ¹⁸⁸W/¹⁸⁸Re generator. Three patients with cancer of the prostate and three with cancer of the bronchus, all with bone metastases confirmed with a standard ^99mTc-hydroxymethylene diphosphonate (^99mTc-HDP) scan, were given 370 MBq ¹⁸⁸Re(V)DMSA and imaged at 3 h and 24 h using the 155-keV γ-photon (15%). Blood and urine samples were collected to determine clearance and to analyse the speciation of ¹⁸⁸Re. Organ residence times were estimated from the scans, and used to estimate radiation doses using MIRDOSE 3. In mice, ¹⁸⁸Re(V)DMSA was selective for bone and kidney. In patients, it showed selectivity for bone metastases (particularly those from prostate carcinoma) and kidney, but uptake in normal bone was not significantly greater than in surrounding soft tissues. Of the normal tissues the kidneys received the highest radiation dose (0.5–1.3 mGy/MBq). The images were strongly reminiscent of ^99mTc(V)DMSA scans in similar patients. High-performance liquid chromatography analysis of blood and urine showed no evidence of ¹⁸⁸Re in any chemical form other than ¹⁸⁸Re(V)DMSA up to 24 h. In conclusion, ¹⁸⁸Re(V)DMSA and its ¹⁸⁶Re analogue warrant further clinical assessment as generator/kit-derived agents for treatment of painful bone metastases. These agents should also be assessed in medullary thyroid carcinoma and other soft tissue tumours which have been shown to accumulate ^99mTc(V)DMSA. Received 8 January and in revised form 28 February 1998     

Technetium-99m human immunoglobulin scintigraphy in psoriatic arthropathy: first results

Standard bone scintigraphy [using technetium-99m methylene diphosphonate (MDP)] is widely held to be the most sensitive method for the early detection of psoriatic arthropathy. Preliminary results of this study reveal that ^99mTc human immunoglobulin (HIG) scintigraphy demonstrates a typical premature pattern of extradermal psoriatic disease in digits indicative of the early stage of psoriatic arthritis. This pattern was also found in a rare case of psoriatic arthropathy without skin lesions. ^99mTc-HIG scintigraphy appears to reveal the initial inflammatory characteristics of later bone lesions. In the advanced stage of psoriatic arthritis, ^99mTc-MDP and ^99mTc-HIG scans were found to be equally sensitive in the detection of the affected joints. Thus ^99mTc-HIG scintigraphy seems to be useful in the early detection of psoriatic arthropathy and also in advanced psoriatic arthritis, as well as for the detection of psoriatic arthropathy without skin lesions. Correspondence to: L. Fridrich     

Binding of99mTc-labelled polyclonal human immunoglobulin to bacteria as a mechanism for scintigraphic detection of infection

The aim of the present study was to determine whether^99mTc-labelled polyclonal human immunoglobulin (^99mTc-HIG) binds to bacteria in vitro as well as in vivo. In vitro, the binding of^99mTc-HIG to various gram-positive and gram-negative bacteria was determined. In vivo, mice were infected withStaphylococcus aureus Cowan I (protein A rich) orS. aureus EMS (protein A deficient) in a thigh muscle and then^99mTc-HIG or^99mTc-labelled human serum albumin (^99mTc-HSA) was administered; scintigrams were made 1, 4, and 18 h later. In vitro binding of^99mTc-HIG to bacteria was higher for gram-positive than for gram-negative forms. A positive correlation was found between the protein A content and the degree of binding toS. aureus. This was also found in vivo. The accumulation of^99mTc-HIG at the site of infection was significantly (P < 0.01) higher than that of^99mTc-HSA, for both strains ofS. aureus. It is concluded that vascular permeability cannot fully explain the accumulation of^99mTc-HIG at the site of infection and that binding of^99mTc-HIG to bacteria plays a role in this respect.     

Synthesis and characterization of [186Re]rhenium(V)dimercaptosuccinic acid: A possible tumour radiotherapy agent

[¹⁸⁶Re]Re(V)DMSA, a β-emitting analogue of the tumour imaging radiopharmaceutical pentavalent [^99mTc]Tc(V)DMSA of possible value in tumour therapy, is readily prepared by stannous reduction of [¹⁸⁶Re]ReO₄⁻ in the presence of dimercaptosuccinic acid at 100°C using a commercial DMSA kit as used for renal imaging with ^99mTc, and purified using a disposable sample preparation column. The complex has been identified as [ReO(DMSA)₂]⁻ by NMR, optical and i.r. spectroscopy and elemental analysis.     

Solitary muscular sarcoidosis: CT,MRI, and scintigraphic characteristics

Scintigraphy using gallium-67 (⁶⁷Ga) citrate and penvaralent technetium-99m dimercaptosuccinic acid {[^99mTc(V)]DMSA} and other radiological examinations were performed in three patients with solitary muscular sarcoidosis who had tumor-like muscular lesions. Although distinction from other invasive soft tissue tumors was difficult using plain and enhanced computed tomography and magnetic resonance imaging, marked uptake of⁶⁷Ga and moderate uptake of [^99mTc(V)]DMSA were shown at the sites of granulomatous inflammatory lesions of sarcoidosis. Both⁶⁷Ga and [^99mTc(V)]DMSA scintigraphy could be of value in the diagnosis and detection of distribution of granulomas of sarcoidosis in the soft tissue and in determining the appropriate region for biopsy.     

The scintigraphy of sacroiliac joints

The accumulation of^99mTc-methylene diphosphonate (99mTc-MDP) and^99mTc-dicarboxypropane diphosphonate (^99mTc-DPD) in sacroiliac (si) joints was evaluated as a function of imaging time in 22 control patients and 5 patients with sacroiliitis. The controls were injected with either^99mTc-DPD or^99mTc-MDP (12 and 10 patients, respectively) and the patients with sacroiliitis with both agents within 5 days. Both the anterior and posterior views of the si joints were taken. The sacroiliac joint-to-sacrum (SI/S) ratio was calculated with the region of interest method. No statistically significant differences between these bone-seeking agents were found in the SI/S ratios of the control or the diseased patients. A clear overlap of indices (mean ± SD) was found between the control patients and the patients with sacroiliitis. When the inflamed si joint was divided into three small adjacent areas and the SI/S ratios calculated for these areas, a statistically significant (P < 0.001) increase in the SI/S ratio was noticed when compared with the SI/S ratio of the whole joint. Comparison of control patients and patients with sacroiliitis showed the most significant differences in the anterior views as well as in theP value:P < 0.001 in all patients injected with^99mTc-DPD and in most patients injected with^99mTc MDP. In the posterior views, the significance was less marked. In every case, the inflamed part of the si joint was visible in the anterior views. The background subtraction had the greatest effect on the SI/S ratio of anterior images, but in the posterior views no significance was found. The low specificity of sacroiliac joint imaging must be taken into consideration when the results are interpreted.     

Technetium-99m labelled hydrazinonicotinamido human non-specific polyclonal immunoglobulin G for detection of infectious foci: a comparison with two other technetium-labelled immunoglobulin preparations

Recently a new linker — hydrazinonicotinate (HYNIC) — was introduced for labelling of proteins and peptides with technetium-99m. HYNIC and other linkers have been used for labelling of human non-specific polyclonal immunoglobulin G (hIgG) with^99mTc for the detection of infections. In this study we compared the tissue distribution of three different^99mTc-hIgG preparations in groups of five Wistar rats with a focal intramuscular infection withStaphylococcus aureus. We compared^99mTc-HYNIC-hIgG with^99mTc-hIgG labelled via the so-called Schwarz method (reduction of disulphide bonds) and with the^99mTc-labelled commercially available Technescan-HIG. Unlike the HYNIC linker, in the two other labelling methods free sulph-hydryl groups are involved in the binding of^99mTc. High-performance liquid chromatography analysis of the labelled preparations and of plasma samples revealed aggregate or polymer formation in all three agents; this was least pronounced in the product labelled by means of the Schwarz method. The tested preparations did not show signs of degradation in vitro. The difference in linker chemistry was reflected in the tissue distribution. Thus the biodistribution of^99mTc-HYNIC-hIgG was significantly different from the distribution of the two other preparations: abscess (1.4%±0.2%ID/g), muscle, liver, spleen, plasma, lung, bone marrow, and small intestine concentrations were higher at 24 h p.i.; kidney uptake (1.19%±0.08%ID/g) was significantly lower. The abscess-to-plasma and the abscess-to-muscle ratios (0.5 and 11, respectively), however, were in the same range for the three preparations tested. Quantitative analysis of the scintigraphs revealed that the total body clearance of^99mTc-HYNIC-hIgG was significantly slower than for the other agents. The abscess uptake of^99mTc-HYNIC-hIgG as a percentage of the remaining body activity was significantly higher. Based on its high abscess uptake, its low uptake in the kidneys and the high percentage of its abscess uptake in relation to the remaining body activity, we conclude that^99mTc-HYNIC-hIgG seems superior to the two other preparations tested for the detection of infections.     

Technetium Tc 99m plasmin in the diagnosis of inflammatory disease

The localization characteristics of technetium Tc 99m plasmin were studied in experimental animals to investigate the use of^99mTc-plasmin for imaging inflammatory processes. At various times after abscess induction using turpentine in rats, the in vivo distribution properties of^99mTc-plasmin, gallium citrate Ga 67,¹²⁵I-fibrinogen, and^99mTc-human serum albumin (HSA) were studied by gamma-camera imaging. The in vivo binding of each radiopharmaceutical was also tested in rat and human plasma clots. Region-of-interest analyses of gamma-camera images showed relatively poor^99mTc-plasmin localization at sites of abscess formation. The ratio of abscess-to-control activity of this radiopharmaceutical did not exceed that of⁶⁷Ga,¹²⁵I-fibrinogen, or^99mTc-HSA. In vitro assays of each of the radiopharmaceuticals in plasma clots showed^99mTc-phasmin and¹²⁵I-fibrinogen to have the best localization characteristics.     

Comparison of reinjection thallium 201 and resting technetium 99m sestamibi tomographic images for the quantification of infarct size after acute myocardial infarction

Background

Both thallium 201 and technetium 99m sestamibi have been used to quantitate infarct size at rest. Exercise²⁰¹Tl scintigraphy has been shown to have powerful prognostic information after myocardial infarction. A single study using these agents that could provide data on infarct size and prognosis would be of value. The purpose of this study was to compare estimates of infarct size by use of²⁰¹Tl and^99mTc sestamibi and to correlate these measurements with left ventricular ejection fraction in patients after acute myocardial infarction.

Methods and Results

The study group consisted of 20 patients who underwent low-level²⁰¹Tl stress studies with reinjection and^99mTc sestamibi resting studies within 4 days. Acute reperfusion was attempted in 18 of 20 patients. For^99mTc sestamibi tomographic imaging, infarct size was quantitated with 60% of maximal counts per slice for five short-axis slices as described in multiple previous studies. The postreinjection delayed²⁰¹Tl images acquired 4 hours after stress were quantitated according to the same threshold method.²⁰¹Tl patient images were also quantitated with a commercially available polar map program and compared with sex-matched control subjects. Ejection fraction was determined for each patient by radionuclide ventriculography 6 weeks later. Ejection fraction was well preserved for the group: mean 0.53±0.10. Infarct size with^99mTc sestamibi was 12%±13% of the left ventricle, which was significantly smaller than either method with²⁰¹Tl: threshold method, 29%±18% of left ventricle; polar map method, 25%±17% of left ventricle (both²⁰¹Tl estimates,p<0.0001 vs^99mTc sestamibi;²⁰¹Tl, 70% threshold vs²⁰¹Tl polar map,p=0.04). There was a significant correlation between infarct size with^99mTc sestamibi and that with²⁰¹Tl (r=0.72 to 0.73;p<0.001). Infarct size with^99mTc sestamibi, however, provided the closest correlation with ejection fraction (r=0.81;p<0.001), with the two²⁰¹Tl quantitative methods providing very similar correlations (r=0.69;p<0.001).

Conclusions

Infarct size with reinjection²⁰¹Tl imaging correlates significantly with resting infarct size with^99mTc sestamibi, although it provides significantly larger estimates. Although both approaches can be combined with a same-day exercise protocol, the closer correlation of infarct size with ejection fraction at 6 weeks suggests that resting infarct size with^99mTc sestamibi may be slightly more accurate.     

A novel electrochemical technique for the production of clinical grade 99mTc using (n, γ)99Mo

IntroductionIn order to meet the growing demand for ^99mTc and to reduce the reliance on fission-produced ⁹⁹Mo, an electrochemical pathway for accessing ^99mTc through the (n, γ)⁹⁹Mo was explored as a back-up measure and to supplement ^99mTc supply for radiopharmaceuticals application.Methods^99mTc from an equilibrium mixture of ⁹⁹Mo/^99mTc was selectively deposited on a platinum cathode in an electrochemical cell by applying optimal voltage and stripped back again into the 0.9% saline solution. The radiochemical and radionuclidic purity of the product were determined using standard techniques. ^99mTc thus obtained was used for labeling standard ligands such as dimercaptosuccinic acid (DMSA) and ethylene dicysteine (EC), to ascertain the usability.ResultsSelective deposition of ^99mTc on the platinum electrode was achieved at a potential of 5 V over a period of 1 h in NaOH electrobath. The overall yield of ^99mTc was >90%, with >99.99% radionuclidic purity and >99% radiochemical purity. The performance of the generator remained consistent over a period of 10 days. The compatibility of the product in the preparation of ^99mTc-labeled formulations such as ^99mTc-DMSA and ^99mTc-EC was found to be satisfactory in terms of high labeling yields (>98%).ConclusionA novel and attractive method has been developed to obtain highly concentrated ^99mTc, without using fission-produced ⁹⁹Mo.     

Comparison of99mTc(V)-DMSA,201Tl and99mTc-MIBI imaging in the follow-up of patients with medullary carcinoma of the thyroid

Radionuclide scanning with tumour-seeking agents such as pentavalent technetium-99m dimercaptosuccinic acid [^99mTc(V)-DMSA], thallium-201 and technetium-99m sestamibi (MIBI) has been reported to be useful in the detection of medullary thyroid carcinoma (MTC). We undertook a study in 14 MTC patients to determine the comparative imaging potential of²⁰¹Tl, MIBI and^99mTc(V)-DMSA in the detection of recurrent or metastatic MTC. All patients underwent total thyroidectomy and had persistently elevated serum calcitonin levels after the surgery. Scintigraphic studies were carried out 20 min after the injection of 111 MBq of²⁰¹Tl or 555 MBq of MIBI and 2 h following the injection of 370 MBq of^99mTc(V)-DMSA. All scintigraphic findings were correlated with contemporaneous CT or MRI studies. CT, MRI and bone scans showed 42 (26 bone, 16 soft tissue) metastatic sites in 11 of the 14 patients. In the remaining three patients no lesions were detected during diagnostic evaluation.^99mTc(V)-DMSA showed all of the soft tissue metastases but could not show two bone lesions. On the other hand, MIBI imaging was false-negative in 22 (52%) sites and²⁰¹Tl was false-negative in 34 (80%) sites. Overall, lesion detection sensitivities for^99mTc(V)-DMSA, MIBI and²⁰¹Tl were 95%, 47% and 19% respectively. We conclude that^99mTc(V)-DMSA is clearly superior to MIBI and²⁰¹Tl in the follow-up of MTC patients.     

Current status of stress myocardial perfusion imaging pharmaceuticals and radiation exposure in Japan: Results from a nationwide survey

Background

Ionizing radiation generated during medical imaging procedures is a matter of concern. However, the current status of radiopharmaceutical use in stress myocardial perfusion imaging (MPI) and the radiation exposure from these radiopharmaceuticals is unknown in Japan.

Methods and Results

A nationwide survey was conducted from June through July 2016. The questionnaires on the radiopharmaceuticals used and their administered doses during stress MPI were sent to 641 nuclear medicine facilities. The responses were collected from 431 facilities and the effective dose (ED) for an adult with standard body weight was calculated. Forty-three percent of the facilities used only ²⁰¹TlCl, 35% used only ^99mTc radiopharmaceuticals, and the remaining 22% used both. The two main reasons for using ²⁰¹TlCl instead of ^99mTc radiopharmaceuticals were “more familiarity with the usage of ²⁰¹TlCl than ^99mTc radiopharmaceuticals” and “apprehension about increasing the burden of physicians performing tracer injection twice.” The mean ED was 14.0 ± 5.5 mSv (range, 3.9 to 25.2 mSv), which was higher than that reported in other countries.

Conclusions

The ED of stress MPI radiopharmaceuticals in Japan is probably higher than the world standard because more than 50% of the facilities still use ²⁰¹TlCl. We recommend revising the routine stress MPI protocol to reduce the effects of ionizing radiation.

     

Apoptotic abscess imaging with 99mTc-HYNIC-rh-Annexin-V

Abscess formation causes systemic and localized up-regulation of neutrophil [polymorphonuclear leukocytes (PMNs)] signaling pathways. In the abscess, following bacterial ingestion or PMN activation by inflammatory mediators, PMN apoptosis is elevated and leads to the externalization of phosphatidylserine. Annexin-V (AnxV) has been shown to have high affinity to externalized phosphatidylserine. We hypothesized that ^99mTc-AnxV will target high densities of apoptotic PMNs and image abscesses. AnxV, conjugated with hydrazinenicaotinamide (HYNIC), was labeled with reduced ^99mTcO₄^? and its purity was determined by instant thin-layer chromatography. Apoptosis was induced in isolated human PMNs by incubation in 2% saline for 17 and 22 h at 37°C. PMNs were then incubated with ^99mTc-HYNIC-AnxV and associated ^99mTc was determined. Abscesses were induced in mice by intramuscular injection of bacteria or turpentine. Following intravenous administration of ^99mTc-HYNIC-AnxV, mice were imaged and tissue distribution studied at 4 and 24 h. Radiochemical purity of ^99mTc-HYNIC-AnxV was 84.9±8.11%. At 17 h, ^99mTc-HYNIC-AnxV bound to apoptotic PMNs was 71.6±0.01% and 48.6±0.01% for experimental and control cells, respectively (P=.002). At 22 h, experimental cells retained 74.9±0.02% and control cells retained 47.2±0.02% (P=.005). ^99mTc-HYNIC-AnxV associated with bacterial abscesses was 1.25±0.09 and 3.75±0.83 percent injected dose per gram (%ID/g) at 4 and 24 h compared to turpentine abscesses which was 1.02±0.16 and 0.72±0.17 %ID/g at 4 (P≤.05) and 24 h (P≤.01). ^99mTc-HYNIC-AnxV represents a minimally invasive and promising agent to image and potentially distinguish between infectious and inflammatory abscesses.     

Retention of technetium-99m in infectious foci in rats after release from technetium-99m labelled human non-specific polyclonal immunoglobulin G: A dual-label study with hydrazinonicotinamido and iminothiolano immunoglobulin

In an effort to contribute to the understanding of the mechanism of uptake of technetium-99m labelled non-specific polyclonal human immunoglobulin G (hIgG) in inflammatory lesions we compared the tissue distribution of double-labelled^99mTc-hydrazinonicotinamido (HYNIC) hIgG-¹⁴C and^99mTc-iminothiolano hIgG-¹⁴C in groups of five Wistar rats with aStaphylococcus aureus infection of the left calf muscle between 2 h p.i. and 24 h p.i. The stability of the two double-labelled hIgG preparations was evaluated in vitro and in plasma in vivo by high-performance liquid chromatography (HPLC) analysis. At 24 h after injection of^99mTc-HYNIC-hIgG-¹⁴C the abscess uptake of^99mTc (1.5% ID/g±0.2% ID/g) was significantly higher (P<0.01) than the¹⁴C uptake (1.0% ID/g±0.1% ID/g). After injection of^99mTc-iminothiolano hIgG-¹⁴C no significant difference (P=0.08) was found between the abscess uptake of the two radionuclides at 24 h p.i. (^99mTc: 0.8% ID/g±0.1% ID/g;¹⁴C: 0.90% ID/g±0.09% ID/g). HPLC analysis of plasma samples revealed release of^99mTc from both double-labelled immunoglobulin preparations. This phenomenon was more pronounced for iminothiolano hIgG than for HYNIC hIgG (43% vs 18%). In most tissues other than abscesses significant differences were also found between the^99mTc and the corresponding¹⁴C uptake. Our results demonstrate that the chemical form in which^99mTc is bound to hIgG severely influences its release from hIgG and its retention in infections.