In vitro adsorption of 99Tc(m)-MIBI, 99Tc(m)-tetrofosmin, 99Tc(m)-furifosmin and 99Tc(m)O4- onto tubes

Adsorption of radiopharmaceuticals onto disposable syringes has been reported to amount to levels of almost 50%. Data on adsorption of radiopharmaceuticals onto materials used for in vitro studies are extremely limited. We assessed the extent of adsorption of 99Tc(m) hexakis(2-methoxyisobutylisonitrile) (99Tc(m)-MIBI), 99Tc(m)-tetrofosmin, 99Tc(m)-furifosmin and 99Tc(m)O4 onto tubes used for in vitro measurement of cellular uptake of these radiopharmaceuticals. The influence on adsorption of different incubation media, temperature and time of incubation was evaluated. Total (not corrected for adsorption) uptake was compared with corrected, net cellular uptake in SK-BR-3, MCF-7 and liposarcoma cell lines. Values of adsorption ranging from 0.94+/-0.13% to 7.07+/-0.46% were found. The extent of adsorption of all the radiopharmaceuticals varied with the type of incubation medium and the incubation temperature. With 99Tc(m)-furifosmin, adsorption was dependent on the incubation time as well on the incubation temperature and some of the incubation media investigated. Our findings indicate that systematic investigations to evaluate the adsorption of radiopharmaceuticals onto materials used during in vitro studies of cellular uptake should be considered a mandatory aspect of quality control.     

Lymphoscintigraphy: a comparison of 99Tc(m) antimony sulphide colloid and 99Tc(m) stannous phytate.

In vitro comparison of 99Tc(m) antimony sulphide colloid and 99Tc(m) stannous phytate as well as in vivo studies in six rabbits and seven patients indicate disparity in the colloidal properties and localization of these two agents. The variability in lymphatic uptake and the relatively poor quality of scintigraphic images following interstitial injection of 99Tc(m) stannous phytate, when compared with 99Tc(m) antimony sulphide colloid, provide evidence of the unsuitability of this agent for lymphoscintigraphy. Maintenance of the diagnostic quality of the lymphoscintigraphic image and adherence to interpretive criteria already established therefore preclude the routine use of 99Tc(m) stannous phytate for interstitial lymphoscintigraphy.     

Evaluation of [(99m)Tc] liposomes as lymphoscintigraphic agents: comparison with [(99m)Tc] sulfur colloid and [(99m)Tc] human serum albumin

This study investigates the use of [(99m)Tc] liposomes for the detection of sentinel lymph nodes. A variety of [(99m)Tc] liposome formulations were compared with common lymphoscintigraphic agents including [(99m)Tc] regular-sulfur colloid (SC), [(99m)Tc] 0.22 microfiltered-SC, [(99m)Tc] reduced heating time 0.22 microfiltered-SC, and [(99m)Tc] human serum albumin (HSA) in rabbits. Images were acquired for the first 60 minutes and at 24 hours, followed by tissue biodistribution study. All agents except [(99m)Tc] regular SC demonstrated good migration from the injection site. Agents were retained in the popliteal node at 24 hours to varying degrees as follows: both [(99m)Tc] filtered SC preparations > [(99m)Tc] regular SC > [(99m)Tc] liposomes > [(99m)Tc] HSA. [(99m)Tc] liposome imaging can be used to develop novel liposome compositions with improved lymph node diagnostic and drug delivery characteristics.     

Value of combined 67Ga and 99Tc(m)-human immunoglobulin G whole-body scanning in malignant lymphoma

Human immunoglobulin G labelled with 99Tc(m) (99Tc(m)-HIG) is an agent introduced for the localization of inflammatory lesions. There is also a limited number of reports concerning the uptake of this agent by malignant lesions. The aim of this study was to evaluate the uptake of 99Tc(m)-HIG by lymphoma. Twenty-three patients (five female, 18 male) with known Hodgkin's or non-Hodgkin's lymphoma for a period of 2-6 years (mean 4.2 years) and which, by using computed tomography (CT), showed recurrence, were included in the study. The patients were aged between 32 and 68 years (mean 38 +/- 5 years). No evidence of inflammation or infection was seen in any of these patients. CT, 99Tc(m)-HIG and a 67Ga scan were performed in the same week. CT showed abdominal involvement in 17 patients, pelvic involvement in 11, and thorax involvement in 11. 99Tc(m)-HIG showed higher sensitivity (94.1%) in the abdomen, a similar sensitivity (63.6%) in thorax, but lower (18.1%) in pelvic area than for 67Ga. 99Tc(m)-HIG was found to be more useful for the evaluation of abdominal involvement compared to 67Ga due to gastrointestinal excretion of the latter. The resolution of 67Ga was better than 99Tc(m)-HIG in thorax and pelvis. Using 99Tc(m)-HIG and 67Ga together in lymphoma may increase sensitivity.     

Osteomyelitis and soft-tissue infection: differential diagnosis with 24 hour/4 hour ratio of Tc-99m MDP uptake

The lesion-to-nonlesion 24 hour/4 hour ratio of technetium-99m methylene diphosphonate (MDP) uptake was used to distinguish osteomyelitis from increased bone uptake caused by adjacent soft-tissue infection. In a prospective study, this ratio was measured in 38 patients with 41 sites of increased uptake that were suspected to be osteomyelitis. The mean ratio was 1.18 +/- 0.18 in patients with proved osteomyelitis, which was significantly higher (P less than .001) than that in patients with increased uptake resulting from soft-tissue infection (0.98 +/- 0.05). On the basis of a receiver operating characteristic curve, a ratio of 1.06 was selected as the cutoff for differentiating osteomyelitis from soft-tissue infection. This method resulted in a sensitivity of 82%, a specificity of 92%, and an accuracy of 85%, and it appears to be more reliable than three- and four-phase scintigraphy, which are subjective and nonquantitative techniques.     

99Tc(m)-tetrofosmin scintimammography for detecting breast cancer: a comparative study with 99Tc(m)-MIBI.

Scintimammography using 99Tc(m)-MIBI (99Tc(m)-sestamibi) has demonstrated promising results in the detection of breast cancer. Recently scintimammography using 99Tc(m)-tetrofosmin has been suggested as a better diagnostic tool and a more convenient agent to use in this condition. In this study we compared both agents in 35 consecutive women with abnormal mammographic or physical findings. Thirty-four of them underwent MIBI scan, followed by tetrofosmin scan 2 days later (performed on all 35 women). Within 2 weeks, a pathological diagnosis was obtained either by needle or open biopsy. In both scans the uptake ratio between the lesion and the background uptake was calculated. Twenty patients who underwent tetrofosmin scan and 19 patients with MIBI scan had malignant breast tumours, while 15 women had benign lesions. The sensitivity, specificity, positive and negative predictive values and total accuracy of the MIBI scan were 89.4%, 80%, 85%, 85.7% and 85.3%, respectively; almost identical values were obtained with tetrofosmin (90%, 80%, 85.6%, 85.7% and 85.7%, respectively). The uptake ratios in the MIBI and tetrofosmin scans were 1.68 +/- 0.52 and 1.7 +/- 0.47, respectively. No differences were found between the two scintimammographies in all the parameters examined. In conclusion, MIBI and tetrofosmin breast scans are accurate and equally efficient for the detection of breast malignancies.     

A comparison in monkeys of (99m)Tc labeled to a peptide by 4 methods.

Although a number of different strategies for labeling peptides with (99m)Tc have been developed, only a few studies have compared the in vivo properties of (99m)Tc when attached to different chelators. Furthermore, these comparisons are usually in mice, whereas results obtained in nonhuman primates may be expected to be more relevant to the clinical situation. METHODS: We evaluated the influence of 4 common chelators on the biodistribution in monkeys of (99m)Tc-labeled HNE-2, a 6.7-kDa peptide being investigated as an inflammation/infection imaging agent. The peptide was conjugated with the N-hydroxysuccinimide ester of mercaptoacetyltriglycine (MAG3), mercaptoacetyltriserine (MAS3), hydrazinonicotinamide (HYNIC), and the cyclic anhydride of diethylenetriaminepentaacetic acid (DTPA). After radiolabeling, each peptide was administered intravenously to rhesus monkeys with a Staphylococcus aureus-induced focal inflammation/infection. RESULTS: Quantification of radioactivity accumulation by regions of interest over 3 h after administration in monkeys showed important differences among labeling methods: For example, at 3 h, kidney accumulation varied in percentage injected dose per organ (%ID per organ) from 31 %ID per organ (HYNIC) to 18 %ID per organ (MAG3), whereas liver varied from 7.8 %ID per organ (MAG3) to 2.8 %ID per organ (MAS3). Radioactivity accumulation in the lesion was independent of labeling method. These organ accumulations were compared with that obtained earlier in mice by sacrifice and dissection also at 3 h and at the same administered dosage. In the rodent, kidney levels varied from 45 %ID per organ (HYNIC) to 12 %ID per organ (MAS3) and liver levels varied from 6.5 %ID per organ (DTPA) to 2.0 %ID per organ (MAS3). CONCLUSION: In agreement with previous work from this laboratory and elsewhere, the method of radiolabeling had an important effect on the biodistribution of (99m)Tc. Furthermore, although biodistribution results in mice should be used with caution to predict biodistributions in primates, in major organs, these results in mice and monkeys were similar.     

Use of (99m)Tc from a commercial (99)Mo/(99m)Tc generator as yield tracer for the determination of (99)Tc at low levels.

The concentrations of (99)Tc and impurity radionuclides in the (99m)Tc tracer solution obtained from a commercial (99)Mo/(99m)Tc generator were measured by gamma spectrometry and liquid scintillation counting. (99)Mo and (103)Ru were found in the (99m)Tc eluate. A simple separation using two extra alumina cartridges was investigated to purify the eluate to obtain a suitable (99m)Tc tracer with low (99)Tc concentration. The activity ratio of (99)Tc/(99m)Tc in the prepared (99m)Tc solution is lower than 15 x 10(-9), which is higher than the theoretical ratio of less than 10 x 10(-9). The possible reason is discussed. The (99)Tc in the 20 kBq spiked (99m)Tc tracer was found to be less than 0.3 mBq, which is lower than the detection limit of the radiometric method used for environmental samples. The purified (99m)Tc eluate is used as yield tracer for the determination of low levels of (99)Tc in environmental samples.     

Bone marrow scintigraphy with 99m Tc labelled monoclonal anti-NCA 90 Fab' fragment: a feasibility study and comparison of bone marrow uptake with 99m Tc labelled monoclonal anti-NCA 95 antigranulocyte antibody

The aim of this retrospective study was to evaluate the usefulness of 99mTc labelled monoclonal anti-NCA 90 antigranulocyte antibody Fab' fragment (MN3 Fab') as a bone marrow imaging agent. One hundred and ten planar scans (88 patients) of the lumbar and sacroiliac regions as well as whole-body scans were performed after 1, 5 and 24 h. All the scans were evaluated visually and bone marrow uptake was determined semiquantitatively as count density ratio from sacroiliac-minus-background to background area. Results were compared to 50 age-matched patients with normal bone marrow scans obtained with the intact 99mTc labelled monoclonal anti-NCA 95 antigranulocyte antibody (BW 250/183) in a previous study. Seventy-three patients showed a physiological activity distribution in the central bone marrow. Ten patients showed a bone marrow extension, while in two patients central bone marrow depression was observed. Evaluation of the ribs, lower thoracic and upper lumbar spine was hampered by soft-tissue activity. Bone marrow uptake was 1.36+/-0.56 after 1 h, decreased thereafter and was significantly lower than that of BW 250/183 (P < 0.001). In conclusion, MN3 Fab' cannot be recommended for bone marrow scintigraphy, because relevant parts of the haemopoietically active bone marrow are not accessible to visual evaluation. A significant role of the semiquantitative evaluation of MN3 Fab' bone marrow uptake in patients with potential marrow depression seems unlikely.     

Usefulness of (99m)Tc(V)-dimercaptosuccinic acid scintigraphy in the assessment of response to external radiation therapy in soft tissue sarcoma in Giant Snauzer dog

A nine-year-old male black Giant Schnauzer dog was referred for the scintigraphic evaluation with a history of malignant fibrosarcoma with a rapidly growing non painful mass on the left shoulder region quite near to the site of an operation performed four months ago. We carried out oncological scintigraphy using pentavalent (99m)Technetium labelled dimercaptosuccinic acid [(99m)Tc(V)-DMSA], a tumour localising radiopharmaceutical agent. The study was performed to assess the margins, vascularity of the tumour and response to the cancer therapy. Uniform intense radiopharmaceutical uptake was observed in the lesion indicating its margins, vascularity and malignant nature. The dog was subjected to external radiation therapy to control the growth of the cancer and to bring the tumour mass to an operable size. The dog was followed up with (99m)Tc(V)-DMSA scintigraphy pre-irradiation and post-irradiation. Immediately after the post-irradiation scintigraphy, the dog was operated on. During the surgery, resection of the tumour margins was performed carefully using a hand held gamma probe to assure that no tumour tissue was left inside. In conclusion, the authors would like to state that (99m)Tc(V)-DMSA oncoscintigraphy is valuable in the assessment and evaluation of therapy in canine soft tissue cancer.     

Calibration of KRISS reference ionization chamber for key comparison of (99m)Tc measurement

KRISS, as the national metrology institute of Korea, has used a reference ionization chamber system to certify the activity of (99m)Tc aqueous sources, but could only recently participate in a comparison exercise by the BIPM (BIPM.RI(II)-K4.Tc-99m) to secure the international equivalence of (99m)Tc radioactivity measurement by way of the BIPM transfer instrument (SIRTI). The KRISS ionization chamber system was calibrated about 100 days before the comparison with a (99m)Tc solution source standardized by the 4πβ(LS)-γ(NaI(Tl)) coincidence counting method. During the comparison, beginning with a higher activity mother solution, the KRISS ionization chamber measured its specific activity without a dilution. The activity of a diluted-solution source was measured by the SIRTI at the same time.     

Active inflammatory bowel disease: head-to-head comparison between 99mTc-hexamethylpropylene amine oxime white blood cells and 99mTc(V)-dimercaptosuccinic acid scintigraphy

PURPOSE: Evaluation and comparison between pentavalent 99mTc dimercaptosuccinic acid (99mTc(V)-DMSA) and 99mTc-hexamethylpropylene amine oxime white blood cell (99mTc-HMPAO WBC) scintigraphy in the detection and assessment of disease activity in patients with active inflammatory bowel disease (IBD). MATERIALS AND METHODS: 99mTc(V)-DMSA scintigraphy was performed in 23 patients with active IBD and true positive 99mTc-HMPAO WBC scintigraphy. Images were considered positive when an area of increased uptake was observed. To assess severity of IBD, semi-quantitative analysis was included with reference to the uptake in the iliac crest. Comparison with endoscopic, radiological and clinical data was performed. RESULTS: The diagnostic accuracy of 99mTc-HMPAO WBC and 99mTc(V)-DMSA was 91% and 84%, respectively. A significant correlation between the findings of both radioisotopic methods and scintigraphy score was demonstrated. Endoscopic findings were significantly correlated with scintigraphic results. Kappa statistics showed a moderate to good agreement between the two scintigraphic methods. Two patients (8.8%) had negative findings with 99mTc(V)-DMSA scintigraphy (false negative results). CONCLUSION: 99mTc(V)-DMSA compared to 99mTc-HMPAO WBC could provide a simple, non-invasive alternative method for the assessment of disease activity, although it is slightly inferior to 99mTc-HMPAO WBC scintigraphy especially in the evaluation of disease localization in IBD patients.     

Radiolabeling of annexin A5 with (99m)Tc: comparison of HYNIC-Tc vs. iminothiolane-Tc-tricarbonyl conjugates

In the perspective of expanding the use of annexin A5 (anx A5) as radioactive tracer of cell death in vivo, we recently described its radiolabeling with (99m)Tc-tricarbonyl [(99m)Tc(H(2)O)(3)(CO)(3)](+) via the mercaptobutyrimidyl group (anx A5-SH). The aim of the present article was to compare this new method with the HYNIC strategy (anx A5-HYNIC), recognized at present as the reference for the radiolabeling of proteins with (99m)Tc. Similar radiolabeling yields and better chemical stability were obtained with the [anx A5-SH-(99m)Tc-tricarbonyl] complex. Since the [anx A5-HYNIC-(99m)Tc(tricine)(2)] conjugate shows isomeric forms which can affect the biological properties whereas [anx A5-SH-(99m)Tc-tricarbonyl] is less or not prone to such drawback, the latter seems superior to the former. Furthermore, (anx A5-SH) is readily obtained via commercial sources of Traut's reagent whereas (anx A5-HYNIC) is not. The results provide encouraging evidence in the development of anx A5-labeled reagent for apoptose imaging.     

The value of Tc99m-diphosphonate (HEDSPA) as a skeletal scanning agent

A new "bone seeking" agent, namely the organic compound diphosphonate labeled with Tc99m was tried in 21 patients for skeletal scanning. In 3 cases, although the clinical and roentgenographic evidence of bone lesions was absent, bone metastases were found, and these were confirmed histologically. The organic diphosphonate is more stable compared to the inorganic polyphosphates and the images obtained are excellent.     

Evaluation of stannous oxidation in the preparation of ultrahigh-purity 99m Tc(V)-DMSA

It has been shown previously that renal kit, trivalent technetium-99m dimercaptosuccinic acid [99mTc(III)-DMSA], can be transformed into tumour imaging agent, pentavalent technetium-99m DMSA [99mTc(V)-DMSA], by adding sodium bicarbonate (NaHCO3) and subsequently bubbling with oxygen. However, the purity of this pentavalent preparation was reported to be in the range 83-94% at best. In this study, the preparation of ultrahigh-purity 99mTc(V)-DMSA is described, and the role of stannous oxidation in the conversion of 99mTc(III)-DMSA to 99mTc(V)-DMSA is evaluated in order to understand the underlying mechanism. The results show that controlled oxygen bubbling increases the 99mTc(V)-DMSA levels, with a concomitant decrease in the 99mTc(III)-DMSA levels, in a time-dependent pattern. The purity of the pentavalent DMSA is shown to be consistently very high (>99%), as estimated by chromatography, and this correlates very well with the minimal or no renal uptake of this compound in patient studies.     

Standardization of (99m)Tc by means of a software coincidence system

The procedure followed by the Nuclear Metrology Laboratory, at IPEN, for the primary standardization of (99m)Tc is described. The primary standardization has been accomplished by the coincidence method. The beta channel efficiency was varied by electronic discrimination using a software coincidence counting system. Two windows were selected for the gamma channel: one at 140 keV gamma-ray and the other at 20 keV X-ray total absorption peaks. The experimental extrapolation curves were compared with Monte Carlo simulations by means of code ESQUEMA.