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 of 67Ga, 125I-fibrinogen, or 99mTc-HSA. In vitro assays of each of the radiopharmaceuticals in plasma clots showed 99mTc-plasmin and 125I-fibrinogen to have the best localization characteristics.     

Thyroid imaging in a typical case of acute suppurative thyroiditis with abscess formation due to infection from a persistent thyroglossal duct

The clinical evaluation of thyroid imaging with^99mTc,²⁰¹T1, and⁶⁷Ga in the uncommon, but potentially serious, disorder of acute suppurative thyroiditis (AST) with abscess formation due to infection from a persistent thyroglossal duct is reported. The^99mTc image showed functioning areas of the diseased thyroid gland and the²⁰¹Tl image demonstrated abscess formation in the thyroid gland of this patient. In addition, marked⁶⁷Ga accumulation was demonstrated in a wide area covering not only the area of the thyroid gland involved, but also associated circumferential inflammatory lesions in a patient with AST. The net thyroid uptake of⁶⁷Ga at 72 hours was calculated to be 13.8% of the injected dose.     

Studies of 99mTc-acylplasmins as agents for thrombus detection

It has been proposed that acylation at the active site of plasmin is able to prevent its reaction with 2-antiplasmin without affecting the fibrin affinity of the enzyme. To investigate the possibility that ^99mTc-labelled acylplasmins are improved thrombus-detecting agents, six acylating agents were synthesised and their reaction with plasmin and the labelling of the products with ^99mTc studies. Uptake of ^99mTc-acylplasmins in an in vitro thrombus model was complicated by precipitation processes, which may in part account for the rapid blood clearance in rabbits and high liver uptake in mice injected with the compounds. Quantitative measurements using an in vivo rabbit thrombus model demonstrated that guanidinobenzoyl-plasmin exhibited nearly a threefold increase in thrombus uptake compared with non-acylated ^99mTc-plasmin. The observed uptake is less than that obtained with ¹²⁵I-fibrinogen at clinically useful time intervals post-injection but represents a significant advantage over the use of ^99mTc-plasmin.     

Return to normal of 99mTc-plasmin test after deep venous thrombosis and its relationship to vessel wall fibrinolysis

Fourteen patients with deep venous thrombosis (DVT) and a positive ^99mTc-plasmin test were followed up to determine how soon a negative test was obtained. Localization and extension of the thrombi were determined by phlebography. Plasminogen activator activity in vein walls and local fibrinolytic activity after venous occlusion were measured in order to find out what the prerequisites for impaired thrombolysis are. The time required to obtain a negative ^99mTc-plasmin test showed considerable variation, ranging from less than 1 week to more than 6 months. The ^99mTc-plasmin test had returned to normal in 64% of the patients after 6 months. No relationship was found between vessel wall fibrinolysis and time to normalization. Instead, we found an association between the time to normalization of the ^99mTc-plasmin test and the size of the thrombus, according to phlebography, as well as between the time to normalization of the ^99mTc-plasmin test and the extension of leg points with a positive ^99mTc-plasmin test at admission. The finding of abnormal ^99mTc-plasmin test at admission. The finding of abnomral ^99mTc-plasmin test results more than 6 months after acute DVT is of practical importance and warrants caution when evaluating patients with symptoms and signs suggestive of acute recurrent DVT.     

Better visualization of a lung tumour with 99mTc-DPD than with 99mTc-glucoheptonate or 67Ga-citrate

A case of a squamous cell lung carcinoma detected with ^99mTc-DPD, ⁶⁷Ga-citrate and ^99mTc-glucoheptonate (GH) is reported. The highest uptake was seen with DPD and the lowest with ⁶⁷Ga. Emission-computed tomography was very useful in DPD imaging but gave less new information in GH and ⁶⁷Ga studies in comparison to traditional planar imaging. The patient had been given both irradiation and chemotherapy, which might be the cause of good accumulation of DPD and rather poor accumulation of GH and ⁶⁷Ga.     

Comparison of technetium-99m methoxyisobutylisonitrile and gallium-67 citrate scanning in the assessment of lymphomas

The aim of this study was to compare the value of scintigraphy using technetium-99m methoxy-isobutylisonitrile (MIBI) with that of scintigraphy using gallium-67 citrate in the assessment of Hodgkin's disease and non-Hodgkin's lymphoma and to relate these results with those of CT scan and MRI. Fifty-eight patients were included either for a follow-up examination or for monitoring of their treatment. Twenty-three residual masses were studied. A whole-body scan was performed, followed by single-photon emission computed tomography (SPET) 20 min after injection of 740 MBq of^99mTc-MIBI and 72 h after injection of 185 MBq of⁶⁷Ga citrate. The overall sensitivity of^99mTc-MIBI and⁶⁷Ga citrate was 71% and 68%, respectively, and the overall specificity was 76% and 44%, respectively. For residual masses, the sensitivity was 44% with both tracers and the specificity was 80% with^99mTc-MIBI and 53% with⁶⁷Ga citrate. The positive predictive values were 85% and 68% and the negative predictive values were 59% and 44%, respectively. The signal-to-background ratio was 1.5 for^99mTc-MIBI and 2 for⁶⁷Ga citrate. At present,^99mTc-MIBI cannot replace⁶⁷Ga citrate in the assessment of lymphomas.     

Renal and extrarenal clearance of99mTc-MAG3: A comparison with125I-OIH and51Cr-EDTA in patients representing all levels of glomerular filtration rate

This investigation was undertaken in order to determine whether the clearance of technetium-99m mercaptoacetyltriglycine (^99mTc-MAG₃) is more closely correlated to the clearance of iodine-125 orthoiodohippurate (¹²⁵I-OIH) than to the clearance of chromium-51 ethylene diamine tetra-acetate (⁵¹Cr-EDTA) and whether there is a clinically significant extrarenal clearance of^99mTc-MAG₃ . Fifty-one patients with a glomerular filtration rate (GFR) of 4–132 ml/min were studied. After a simultaneous single injection of the three tracers, plasma clearance was measured from blood samples 0–5 h post injection (p.i.) (0–24h in patients with GFR<15 ml/min). Renal plasma clearance was measured 0–5 h p.i. The ratio between the renal plasma clearance of^99mTc-MAG₃ and¹²⁵I-OIH was 0.57. The ratio between the renal plasma clearance of^99mTc-MAG₃ and⁵¹Cr-EDTA was 2.57. The coefficient of variation (CV) of the^99mTc-MAG₃/¹²⁵I-OIH ratio was significantly smaller than the CV of the^99mTc-MAG₃/⁵¹Cr-EDTA ratio (13.4% versus 31.2%). The corresponding plasma clearance ratios were 0.59 (CV=14.8%) and 2.48 (CV=27.0%). Plasma clearance overestimated renal plasma clearance by 7.0 ml/min (5.4%) for^99mTc-MAG₃ and by 4.1 ml/min (8.4%) for⁵¹Cr-EDTA. The difference in plasma and renal plasma clearance of¹²⁵I-OIH of 5.5 ml/min did not reach statistical significance. Red blood cell binding of^99mTc-MAG₃,¹²⁵I-OIH and⁵¹Cr-EDTA was 2.0%, 14.6% and 0.2%, respectively. Protein binding of^99mTc-MAG₃,¹²⁵I-OIH and⁵¹Cr-EDTA was 86.3%, 61.1% and 5.9%, respectively. The volume of distribution of^99mTc-MAG₃,¹²⁵I-OIH and⁵¹Cr-EDTA was 16.3%, 27.0% and 19.4% of body weight. In conclusion, the clearances of^99mTc-MAG₃ and¹²⁵I-OIH are more closely correlated than is the clearance of^99mTc-MAG₃ with GFR. Extrarenal clearance of^99mTc-MAG₃ is relatively smaller than extrarenal clearance of⁵¹Cr-EDTA. Thus, plasma clearance of^99mTc-MAG₃ can be used as a measure of renal tubular function.     

The complementary role of sequential 99mTc-MDP and 67Ga-citrate scanning in the diagnosis and follow-up of neuroblastoma

Fourteen children with histopathologically confirmed neuroblastoma underwent 38 studies using ^99mTc-methylene-diphosphonate (MDP) and galliumcitrate Ga67 whole-body scintigraphy during various stages of the disease. Ten patients (71%) showed ^99mTc-MDP accumulation in the primary tumoral site, whereas 11 patients (78.6%) showed ⁶⁷Ga concentration. In 12 patients (86%), at least one of these two radiopharmaceuticals concentrated in the primary tumor. Nine patients had osseous or extraosseous metastases. All of these metastases (100%) were positive on ^99mTc-MDP sctintigraphy. No ⁶⁷Ga-citrate uptake was demonstrable in osseous metastases; only one extraosseous lung metastasis concentrated this radiopharmaceutical. ⁶⁷Ga-citrate was superior to ^99mTc-MDP with regard to accurately demonstrating the extent of primary tumors. Only ^99mTc-MDP indicated the relationship of the tumor to the kidneys and neighbouring osseous structures, prividing early screening of kidney compression and possible damage caused by the tumor. From these results, we found these two methods to be complementary for the diagnosis and follow-up of neuroblastoma; their combined use resulted in high diagnostic accuracy and a considerable gain of information. We therefore recommend sequential ^99mTc-MDP and ⁶⁷Ga-citrate scans for the diagnosis and evaluation of the primary tumor; periodic ^99mTc-MDP wholebody scans should be used in the follow-up of treatment, and for discovering disease exacerbations and metastases.Presented in part in the European Congress of Nuclear Medicine, London, England, September 1985     

The behavior of99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO) in blood and brain

^99mTc-hexamethylpropyleneamineoxime (^99mTc-HMPAO) is a reagent for scanning cerebral blood flow. We investigated how^99mTc-HMPAO changed in the blood and brain. The^99mTc-HMPAO, which was prepared by adding of^99mTcO _- ⁴ to HMPAO and Sn(II), consisted of primary and secondary complexes, reduced hydrolyzed^99mTc, and^99mTc0pertechnetate. The percentage of the primary complex in^99mTc-HMPAO decreased with time after preparation. The primary complex converted to the secondary one very rapidly in the presence of plasma. When^99mTc-HMPAO was injected into patients,^99mTc activity was immediately partitioned in the plasma fraction, with approximately 60% in whole blood. In plasma,^99mTc was found to be associated with proteins such as albumin and globulin.^99mTc trapped in red cells was not washed out with either plasma or saline. Biodistribution studies showed that the less lipophilic compounds of^99mTc-HMPAO could not pass through the blood brain barrier (BBB), and therefore did not accumulate in the brain. The results of gel chromatography and equilibrium dialysis indicated that no specific^99mTc binding protein was present in the brain. Considering the instability of^99mTc-HMPAO in vivo, we proposed that the speed at which the primary complex converted to the less lipophilic compounds was important in allowing^99mTc-HMPAO to pass through the BBB and to be fixed in the brain.     

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.     

99mTc-methylene diphosphonate and 67Ga-uptake in myositis ossificans

A histologically proven case of myositis ossificans is presented. Both ^99mTc-MDP and ⁶⁷Ga imaging demonstrated extensive uptake of radiotracers in the lesion.     

Technetium-99m-L,L-ethylenedicysteine scintigraphy in patients with renal disorders

Technetium-99m-L,L-ethylenedicysteine (^99mTc-L,L-EC), a new renal imaging agent, was introduced as an alternative to^99mTc-mercaptoacetyltriglycine (MAG3). This radiopharmaceutical can be easily labelled at room temperature and has high radiochemical purity and long stability. The aim of this study was to gain clinical experience in using^99mTc-L,L-EC in normal volunteers and patients. The clearance of this radiopharmaceutical was compared with that of iodine-131ortho-iodohippurate (OIH) in five healthy volunteers. In addition, conventional renogram and whole-body distribution of^99mTc-L,L-EC (40 min and 3 h post-injection) were evaluated in these subjects. Subsequently, ten patients with suspected obstructive nephropathy, four with renovascular disorders and two in acute renal failure were imaged. In five patients with impaired renal function both^99mTc-MAG3 and^99mTc-L,L-EC studies were performed. In each case the scintigraphic images and time/activity curves were evaluated and various semiquantitative parameters calculated and compared. No adverse effects were noted during and after^99mTc-L,L-EC scintigraphy. The mean clearance values for^99mTc-L,L-EC and¹³¹I-OIH in volunteers were 504 and 663 ml/min respectively. The total plasma clearance of^99mTc-L,L-EC was about 75.8% of the¹³¹I-0IH value. In volunteers the parenchymal transit time index, whole kidney transit time index and mean parenchymal transit time for^99mTc-L,L-EC were 63 s, 124 s and 175 s respectively. The mean time to peak activity was 235 s and the time from peak to 50% of peak activity was 402 s. In all patients the results of scintigraphy were concordant with clinical findings and subsequently influenced patient management. Furthermore,^99mTc-L,L-EC scintigraphy provided high-quality images similar to those obtained with^99mTc-MAG3, even at low glomerular filtration rates (18 ml/min). It is concluded that^99mTc-L,L-EC has excellent imaging characteristics similar to^99mTc-MAG3 and excretion properties similar to OIH. This radiopharmaceutical can be used routinely to evaluate patients with renal disorders.     

99mTc-NC100668, a new tracer for imaging venous thromboemboli: pre-clinical biodistribution and incorporation into plasma clots in vivo and in vitro

Purpose

^99mTc-NC100668 is a new radiotracer being developed to aid the diagnosis of thromboembolism. The structure of NC100668 is similar to a region of human α₂-antiplasmin, which is a substrate for factor XIIIa (FXIIIa). The purpose of this study was to confirm the uptake of ^99mTc-NC100668 into forming plasma clot and to establish the biodistribution of ^99mTc-NC100668 in Wistar rats.

Methods

The in vitro plasma clot uptake of ^99mTc-NC100668 and other compounds with known affinities to FXIIIa was measured using a plasma clot assay. The biodistribution and blood clot uptake of radioactivity of ^99mTc-NC100668 in normal Wistar rats and those bearing experimentally induced deep vein thrombi were investigated.

Results

The in vitro uptake of ^99mTc-NC100668 was greater than that for [¹⁴C]dansyl cadaverine, a known substrate of FXIIIa in the plasma clot assay. The biodistribution of ^99mTc-NC100668 in male and female Wistar rats up to 24 h p.i. showed that radioactivity was rapidly excreted, predominantly into the urine, with very little background tissue retention. In vivo the uptake and retention of ^99mTc-NC100668 into the blood clot was greater than could be accounted for by non-specific accumulation of the radiotracer within the blood clot.

Conclusion

^99mTc-NC100668 was retained by plasma clots in vitro and blood clots in vivo. No significant tissue retention which could interfere with the ability to image thrombi in vivo was observed. This evidence suggests that ^99mTc-NC100668 might be useful in the detection of thromboembolism.     

Evaluation of Tc-99m(V) DMSA for imaging inflammatory lesions: An experimental study

The present study evaluated^99mTc(V) DMSA as an agent for the visualization of inflammatory lesions in comparison to^99mTc(HI) DMSA and^99mTc-HIG. All three radiopharmaceuticals were prepared with commercial kits.^99mTc(V) DMSA was prepared at neutral pH by the addition of first bicarbonate and then pertechnetate to the kit contents. The labeling efficiency was 99% as determined by ITLC. Abscesses were induced by i.m. injection of 50 μl turpentine into the right thighs of 36 Swiss albino mice. Six days later 3.7 MBq of each radiopharmaceutical was i.v. administered to 12 mice. The mice were sacrificed at 1,3,6 and 24 h later. Scintigrams were obtained with a gamma camera. The abscesses were better visualized on scintigrams with^99mTc(V) DMSA compared to^99mTc(III) DMSA, starting at 1 h. The animals were dissected and the organs were removed, weighed and the radioactivity determined with a gamma counter. The abscess to other tissue ratios were higher with^99mTc(V) DMSA than the other radiopharmaceuticals. The max. abscess/muscle ratios were 9.46 ± 3.20 (24 h), 4.19 ± 1.39 (6 h) and 5.98 ± 1.17 (24 h) and max. abscess/blood ratios were 6.22 ± 1.41, 4.09 ± 0.84 and 0.914 ± 0.351 all at 24 h for^99mTc(V) DMSA,^99mTc(III) DMSA and^99mTc-HIG, respectively. Experimental arthritis was produced in 6 New Zealand white rabbits by intra-articular injection of ovalbumin. Four days later 37 MBq of^99mTc(V) DMSA and^99mTc-HIG were each i.v. administered to 3 rabbits. Scintigrams obtained at 1, 3, 6, and 24 h clearly demonstrated arthritic joints. ROFs over arthritic joints were compared to contralateral normal joints (A/C). The max. A/C ratios were 2.10 ± 0.31 (3 h) and 2.92 ± 0.99 (24 h) for^99mTc(V) DMSA and^99mTc-HIG, respectively. Our results indicated the feasibility of imaging inflammatory lesions with^99mTc(V) DMSA.     

Macrophage targeting with technetium-99m labelled J001 acylated poly-galactoside for scintigraphy of inflammation: Optimization and assessment of imaging specificity in experimental arthritis

J001, an acylated poly-(1,3)-galactoside purified from the membrane ofKlebsiella pneumoniae, associates selectively with macrophages via the binding to CD11b and CD14 molecules. Inflammatory foci known to recruit macrophages could thus be imaged with technetium-99m labelled J001. This study aims to define the optimal scintigraphic protocol for^99mTc-J001 imaging and to evaluate the specificity of J001 scans. A dose range study was conducted in rabbits with immunological arthritis using six different specific activities ranging from 370 to 11840 MBq·mg^–1 while the intravenously injected activity was constant (37 MBq) Radiochemical purity for each preparation was documented together with the in vivo stability of the^99mTc-J001 complex using exclusion-diffusion radioHPLC of serum collected 1 h after radiopharmaceutical administration. Scintigraphic images were recorded at 2, 3 and 4 h and analysed using indexes calculated from regions of interest. Specificity of the macrophage imaging was assessed by comparison with scans obtained after administration of^99mTcO₄ ^– or^99mTc-albumin nanocolloids. A protocol of plasma transfusion was also used to inject^99mTc-J001 after complete removal of radioactive colloids likely to be generated during the labelling. For the higher specific activities (5920 and 11840 MBq·mg^–1), radiochemical purity degradation and in vitro^99mTc transchelation were noted. To prevent transchelation and^99mTc bond hydrolysis likely to impair imaging specificity, 1480 MBq·mg^–1 corresponding to 25 µg injected J001 was found to be the optimal usable specific activity. Results obtained with the various tracers support the hypothesis that macrophage targeting is the main factor involved in the J001 imaging of arthritis.     

Comparison of technetium 99m-phytate and technetium 99m-sulphur colloid in primary bone tumours

Eleven patients with proven primary bone tumour (five Ewing sarcomas, six osteosarcomas) and two cases of metastatic bone involvement (primary other than bone) were investigated with^99mTc-phytate and^99mTc-sulphur colloid to compare the behaviour of the two radiopharmaceuticals at the tumour site. After intravenous administration of the respective radiopharmaceutical, imaging of the tumour site and its contralateral part was carried out at 15 min and 1 h intervals. The data were stored in our computer. Bone scanning was also carried out in all patients.^99mTc-phytate uptake was observed at the tumour site in ten cases. The^99mTc-sulphur colloid study revealed sparse or no significant uptake in eight cases. In two patients, with osteosarcoma^99mTc-sulphur colloid investigation showed uptake at the primary tumour site. However, the distribution pattern is different from that of^99mTc-phytate. No significant uptake of either 99mTc-phytate or^99mTc-sulphur colloid was observed in the two patients with metastatic skeletal disease. It may be concluded that the unusual accumulation of^99mTc-phytate at the tumour site is not due to any generalized reticuloendothelial phenomenon and that the radiopharmaceutical itself is responsible for this.     

Cardiac and skeletal muscle scintigraphy in dermato- and polymyositis: Clinical implications

To determine the role of scintigraphy in the detection of skeletal and cardiac involvement in dermato-and polymyositis (DM/PM), we studied 30 patients with a confirmed diagnosis of DM/PM (23 females, 7 males; mean age: 35 years). Technetium-99m pyrophosphate (^99mTc-PYP) and gallium-67 scans showed similar sensitivity, specificity and accuracy in the detection of skeletal muscle involvement when compared with serum enzymes (70%, 100% and 80%, respectively). Compared with the clinical parameters,^99mTc-PYP showed 70% and⁶⁷Ga 65% accuracy. Abnormal PYP cardiac uptake was observed in 57% of patients, whereas abnormal⁶⁷Ga cardiac uptake was seen in only 15%. Electrocardiography was abnormal in 40%, rest gated blood pool study in 23%, and chest X-ray in 13%. In conclusion, both^99mTc-PYP and⁶⁷Ga can be useful in the detection of the active phase of muscle disease. However,^99mTc-PYP seems to be more effective than⁶⁷Ga in the early diagnosis of cardiac involvement.     

Synthesis and evaluation of a novel 68Ga-chelate-conjugated bisphosphonate as a bone-seeking agent for PET imaging

Introduction

⁶⁸Ga is a positron-emitting nuclide that has significant imaging potential given that, unlike cyclotron-produced ¹⁸F, the isotope can be produced on-site utilizing a ⁶⁸Ge/⁶⁸Ga generator. We recently synthesized a novel bone-seeking agent by coupling a bisphosphonate with the ⁶⁸Ga chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). This study presents a first report on the potential of this ⁶⁸Ga bone-seeking radiopharmaceutical in the detection of bone metastases.

Methods

4-Amino-1-hydroxybutylidene-1,1-bisphosphonate was conjugated with 2-[4,7-di(carboxymethyl)-1,4,7-triazonan-1-yl]pentanedioic acid, yielding 2-[4,7-di(carboxymethyl)-1,4,7-triazonan-1-yl]-5-[(4-hydroxy-4,4-diphosphonobutyl)amino]-5-oxopentanoic acid (NOTA-BP). ⁶⁸Ga-labeled NOTA-BP ([⁶⁸Ga]NOTA-BP) was prepared by complexation of NOTA-BP with [⁶⁸Ga] gallium chloride and evaluated in in vitro experiments, biodistribution experiments and micro-positron emission tomography (PET) imaging experiments.

Results

The labeling of NOTA-BP with ⁶⁸Ga was completed by heating for 10 min. [⁶⁸Ga]NOTA-BP was determined to have a radiochemical purity of over 95%, a high affinity for hydroxyapatite and a high stability in plasma. In in vivo biodistribution experiments, [⁶⁸Ga]NOTA-BP demonstrated high bone uptake potential. Compared with ^99mTc-labeled methylene diphosphonate ([^99mTc]MDP) and [¹⁸F]fluoride, [⁶⁸Ga]NOTA-BP exhibited faster blood clearance and a higher bone-to-blood ratio. In addition, mouse model bone metastasis was detected by micro-PET imaging at 1 h postinjection of [⁶⁸Ga]NOTA-BP.

Conclusion

We have developed a novel ⁶⁸Ga-radiolabeled bone-seeking agent. This [⁶⁸Ga]NOTA-BP complex was found to have a high bone affinity and rapid blood clearance, and may thus prove to be useful as a bone-seeking agent for clinical PET.     

Technetium 99m mercaptoacetyltriglycine gamma camera clearance calculations: methodological problems

Major sources of errors in the gamma-camera methods for the calculation of renal clearance are the accuracy of background correction for obtaining the true renal time-activity curve and the validity of the externally recorded pre-cordial activity as an estimate of the plasmatic time-activity curve. With technetium 99m mercaptoacetyltriglycine (^99mTc-MAG3), because of its high protein plasma binding, one could expect minimal extravascular diffusion and hence a more accurate externally detected plasmatic curve. The high extraction rate should reduce the influence of the background, but, on the other hand, the effect of hepatobiliary excretion on the calculation of renal clearance might be significant. Our results suggest that the hepatobiliary excretion of^99mTc-MAG3 does not influence the gamma-camera renal clearance determination, even in patients with low renal function. However, the pre-cordial curve does not reflect accurately the plasmatic disappearance curve; its calibration with a single plasma sample taken at the 20th min is responsible for significant errors, probably because of an unfavourable ratio between the intravascular and extravascular activities at the 20th min. Offprint requests to: M. TondeurParts of this work have been presented at the 17th Annual Meeting of the British Nuclear Medicine Society, London, in April 1989.     

Can technetium 99m bisdiethylphosphinoethanebis-t butylisocyanide (99mTc-DEPIC) be used for routine radionuclide ventriculography?

Radionuclide ventriculography is a useful investigation in the evaluation of cardiac function. Generally, in vivo technetium 99m-labelled red blood cells (RBC) yield good quality images in ventriculography. However, it is widely believed that some drugs have an adverse effect on RBC labelling. Zanelli et al. (1987) developed a radiopharmaceutical (technetium 99m bisdiethylphosphinoethanebis-t-butylisocyanide,^99mTc-DEPIC) to obtain better results in patients using such drugs. We untertook a prospective study of 6 patients with cardiovascular and/or pulmonary disease using several kinds of drugs to evaluate imaging of the cardiac blood pool with^99mTc-DEPIC and in vivo labelled^99mTc-RBC. After injection, blood samples were taken, and gated equilibrium blood pool studies were performed. The radiochemical purity of the injected^99mTc-DEPIC varied from 76.4 to 93.6% (mean 86.4%, SD 5.7%). The protein (pre-albumin) binding was 100%. Biological half-life in blood varied from 3.3 to 4.7 h (mean 4.1 h, SD 0.5 h). For^99mTc-RBC no significant blood disappearance was seen for 8 h. The percentage of RBC-bound^99mTc varied from 96.9% to 98.3% (mean 97.0%, SD 0.5%) and was stable for at least 8 h. The heart-to-lung, heart-to-spleen, and heart-to-liver ratios were higher for^99mTc-RBC than for^99mTc-DEPIC. Furthermore,^99mTc-DEPIC showed a significant decline of the ejection fraction with time. Visually, the images with^99mTc-RBC were superior to those with^99mTc-DEPIC, especially a few hours after injection. According to our findings, in vivo labelling of^99mTc-RBC is still the method of choice for routine radionuclide ventriculography. The decline of the ejection fraction, the short blood half-life, and the intense liver uptake make^99mTc-DEPIC less suitable for this purpose.