Scintigraphy for detecting tumour necrosis factor-α on the skin of patients with psoriatic arthritis.

OBJECTIVE: This study assessed the use of scintigraphy and magnetic resonance imaging (MRI) in identifying the presence and amount of tumour necrosis factor-α (TNF-α) in the joint or skin of patients with psoriatic arthritis, to guide the course of treatment more efficiently. METHOD: We compared the results of scintigraphy and MRI in two patients with psoriatic arthritis who underwent technetium-99m (99mTc)-anti-TNF-α scintigraphy, and MRI 5 days later. RESULTS: Greater uptake of 99mTc-anti-TNF-α was observed in the left wrist and right second metacarpal in patient 1, and in the left ulnocarpal joint and distal interphalangeal joint of the left first metacarpal in patient 2. These results correlated with the MRI findings. CONCLUSIONS: 99mTc-anti-TNF-α scintigraphy may recognize the molecule involved in the inflammatory process. This may provide crucial information to help physicians make decisions about which drugs to use based on biological evidence, and which are cost-effective and appropriate for the treatment of choice. To the best of our knowledge, this is the first time that TNF-α has been shown in the skin of a patient using diagnostic imaging methods.

Radioactive synovectomy with (90) yttrium and (153) samarium hydroxyapatite in haemophilic joints: preliminary study on radiation safety.

Most countries still do not achieve 1 IU of factor VIII/capita sufficient for survival. Although primary prophylaxis prevents synovitis, is not universally used. Chronic synovitis is treated with arthroscopy at expense of considerable amount of coagulation factors, and specialized surgeons. Radioactive synovectomy (RS) is a minimally invasive and cost effective alternative to arthroscopy, often considered first the option for persistent synovitis. Even without established causation with cancer, RS is avoided by some, due to this concern. We aim contributing to the understanding of RS safety regarding malignancy, presenting a large number of treated patients, and a single case of cancer. Three centres in Brazil applied RS with (90) Yttrium Citrate, (90) Yttrium hydroxyapatite or (153) Samarium hydroxyapatite in haemophilic joints and performed a survey addressing cancer in these patients. Four hundred and eighty eight patients (ages 3-51) received 1-3 RS (total 842) and follow-up was 6 months to 9 years. One patient aged 14 years presented Ewing sarcoma, 11 months after RS. The tumour was treated successfully with surgery and chemotherapy. Causality of cancer by RS is improbable in this case. Accordingly, latency here is far below minimum 5-10 years for radio-induction of solid tumours. Moreover, ES is not a typically radio-induced tumour, even at high doses. In agreement with others, though recognizing limitations, this study suggests RS is safe regarding cancer induction. Synovitis is a known burden for patients. The decision of making reasonable usage of RS should be outweighed with the risks of leaving synovitis untreated.

A pilot study evaluating 99mTc-anti-TNF-alpha scintigraphy in graves' ophtalmopathy patients with different clinical activity score.

The present study describes the preliminary results of the use of 99mTc-anti-TNF-α scintigraphy as a new diagnostic approach to evaluate patients presenting with Graves' ophthalmopathy (GO). Patients (n=25) presenting at different inflammatory stages of GO and 10 healthy volunteers underwent 99mTc-anti-TNF-α scintigraphy. Images were obtained 15 min after the intravenous injection of 370 MBq (10 mCi) 99mTc-anti-TNF-α. Planar images were obtained in a 256×256 matrix (each lasting 5 min) and single photon emission computed tomography (SPECT) scan lasting 13 min. Regions of interest (ROI) were drawn on the orbit and cerebral hemispheres. The uptake of 99m Tc-anti-TNF-α in these regions was compared and positive scintigraphy established when the ROI was >2.5. In addition, uptake for each positive exam was scored as either slight (2.6-5.1), moderate (5.2-7.6), or high (>7.6). In this pilot study, 69 orbits were evaluated (1 patient had only 1 eye), and 27 had a positive CAS (≥3/7). Scintigraphies were positive in 38 orbits. Comparing the results of the exams with CAS, a high sensitivity and negative predictive values were determined for scintigraphy (96.3% and 96.7%, respectively). However, the specificity and the positive predictive values were 71.4% and 68.4%, respectively, with an accuracy of 81.2%. The exclusion of examinations that were slightly positive from the analysis resulted in an improvement in test accuracy (95.5%). The preliminary results suggest that 99mTc-anti-TNF-α scintigraphy is a promising procedure for the evaluation of active orbital inflammation in GO.

9°Yttrium-hydroxyapatite: a new therapeutic option for radioactive synovectomy in haemophilic synovitis.

Recurrent haemarthroses often lead to chronic synovitis in patients with haemophilia and von Willebrand disease. Radioactive synovectomy with yttrium-90 (9°Y) citrate is frequently used to treat this complication, usually with good results. Since 2006, the Nuclear Energy Research Institute (IPEN, Sao Paulo, Brazil) has produced hydroxyapatite particles labelled with 9°Y for radioactive synovectomy. The aim of this study was to compare the results achieved by both forms of 9°Y in the treatment of haemophilic synovitis. We included 221 joints from 136 patients (age range: 6-20 years), treated by one of the two radiopharmaceuticals, at the Hemocenter of Mato Grosso, Brazil. The outcomes analysed were the annual frequency of haemarthrosis, articular pain and joint range of motion before and 1 year after RS. Similar results were achieved regardless of whether 9°Y hydroxyapatite or 9°Y citrate was used, and results were independent of the joint type, age, gender, radiologic stage and presence of inhibitors. 9°Y hydroxyapatite appears to be equivalent to the reference product 9°Y citrate in the treatment of chronic synovitis associated with bleeding disorders.

Bone marrow cell transplant does not prevent or reverse murine liver cirrhosis.

We tested the effect of bone marrow cell (BMC) transplantation in either preventing or reversing cirrhosis on an experimental model of chronic liver disease. Female Wistar rats were fed a liquid alcohol diet and received intraperitoneal injections of carbon tetrachloride (CCl4) over 15 weeks. Ten animals (cell-treated group) received five injections of BMCs during the cirrhosis induction protocol (on the 4th, 6th, 8th, 10th, and 12th weeks) and four animals received the cells after liver injury was established through tail vein. Nine animals (nontreated group) were submitted to the previously described protocols; however, they received vehicle injections. Analyses were performed to verify whether the infusion of cells was effective in preventing the development of cirrhosis in our model of induction, and if the cells could reverse cirrhosis once it was established. Hepatic architecture and fibrotic septa were analyzed in liver slices stained with hematoxilin & eosin and Sirius red, respectively. Fibrosis quantification was measured by Sirius red histomorphometry. Indirect immunofluorescence was performed to detect the amount of tissue transglutaminase 2. Blood analyses were performed to assess liver injury and function by the assessment of alanine aminotransferase and albumin. Ultrasound was performed to analyze the portal vein caliber and presence of ascitis. Cirrhosis features (regenerative nodules and fibrous septa) were observed in histopathology after 15 weeks of continuous hepatic injury in nontreated and cell-treated groups. Collagen content, immunofluorescence analysis, and biochemical and ultrasound parameters were similar in nontreated and cell-treated groups; however, both groups showed significant differences compared to a normal control group. Cell infusions with bone marrow-derived cells seem to be ineffective in improving morphofunctional parameters of the liver when applied to chronic cases either during or after establishment of the hepatic lesion.

Radioguided occult lesion localization (ROLL) and excision of breast lesions using technetium-99m-macroaggregate albumin and air injection control.

The aim of this study was to assess the efficiency of the radioguided localization and excision technique using radiopharmaceuticals injected directly or close to occult breast lesions. We studied thirty-two consecutive patients with thirty-six occult breast lesions detected mammographically or ultrasonically categorized as BI-RADS 3, 4 or 5. Macroaggregate Albumin (MAA) labeled with (99m)Tc was administered directly or close to the lesion, guided by mammography or ultrasound, followed by an air injection for radiological control. The excision biopsy was carried out with the aid of a hand-held gamma detecting probe and the entire removal of the lesion was verified by X-ray of the surgical specimens or by intraoperatory frozen section examination. Breast cancer was found in 8.3% of BI-RADS 3 lesions, in 33.3% of the BI-RADS 4 lesions and in 66.6% of the BI-RADS 5 lesions. The radiotracer was correctly positioned in 97.2% of the specimens (35/36) allowing the removal of 97.2%. Xray confirmed the entire removal in 27 lesions (75%), intraoperatory frozen section study in 19.4% (7/36) and by both methods in 5.5% (2/36). Radioguided surgery turned out to be an important tool in the removal of non-palpable breast lesions, as a simple, fast and feasible method that can be implemented in the clinical routine of patients with non-palpable breast lesions.

Sentinel node identification by scintigraphic methods in cutaneous melanoma.

In melanoma patients lymph node metastasis is an important prognostic factor that indicates the need for therapeutic lymph node dissection. Preoperative lymphoscintigraphy mapping associated with radioguided sentinel lymph node biopsy has become a well established procedure for cutaneous melanoma patients without clinically detectable lymph node metastases (stage I, II). This technique is a versatile way of characterizing the lymphatic basin at risk for metastases and identifying involved lymph nodes. The purpose of the present study was to examine the reproducibility of lymphoscintigraphy and sentinel lymph node biopsy in detecting micro metastases in cutaneous melanoma. The study was a single-institution prospective analysis of 74 melanoma patients, with primary tumors having Breslow thickness > 0.7 mm, who underwent lymphoscintigraphies between May 2002 and September 2003. Technetium-99m sulfur colloid was injected intradermally at the primary tumor site and dynamic images were obtained for 40 minutes. Two observers evaluated the images. One to two weeks after the first lymphoscintigraphy, radioguided lymph node biopsy was performed. For the biopsy, technetium-99m sulfer colloid was injected intradermally in the same manner as performed before. Lymph nodes were identified and removed with the aid of a gamma ray detecting probe (GDP), and were submitted to histopathological analysis. The histopathological analysis of the sentinel lymph nodes collected during surgery was performed in a sequential manner. First, frozen sections were analyzed during surgery. The lymph nodes considered negative by frozen section were analyzed by H&E staining. Subsequently, the slides considered negative with H&E were sent for immunohistochemical analysis. Lymphoscintigraphy identified at least one sentinel lymph node in all patients. Sentinel node biopsy detected metastases in 20 patients (27.2%). In all cases the lymph node basins identified during lymphoscintigraphy were found to have at least one sentinel lymph node during surgery. Frozen section analysis of the lymph node was only able to identify the disease in 35% of the patients eventually found to have micrometastases with H&E and immunohistochemistry. Two lymph nodes were negative with H&E and positive with immunohistochemical analysis. In conclusion, lymphoscintigraphy is a simple procedure that is well tolerated by patients. It is useful in locating sentinel lymph nodes in patients with melanoma and is an important tool in the clinical practice of oncology. We recommend performing H&E, and if necessary, immunohistochemical analysis of all sentinel lymph nodes because of the high rate of false negative results with frozen sections alone.

Use of (99m)Tc-doxorubicin scintigraphy in females with breast cancer: a pilot study.

OBJECTIVE: Doxorubicin (Eurofarma, São Paulo, Brazil) is an antitumour agent widely used in the treatment of breast cancer and can be used for tumour tracking when labelled with a radionuclide. Here, we present the results obtained with technetium-99m ((99m)Tc)-doxorubicin, using the direct method, to evaluate its uptake in breast cancer. METHODS: Four females with confirmed breast carcinoma diagnosis and breast image reporting and data system Category 5 on mammography underwent whole-body and thorax single-photon emission CT/CT imaging 1 and 3 h after (99m)Tc-doxorubicin administration. RESULTS: We observed increased uptake in breast carcinoma lesions and elimination via renal and hepatic pathways. CONCLUSION: These preliminary results suggest that (99m)Tc-doxorubicin may be a promising radiopharmaceutical for the evaluation of patients with breast cancer. Further studies are ongoing. ADVANCES IN KNOWLEDGE: To our knowledge, this is the first study to evaluate the use of a directly labelled doxorubicin tracer in humans. (99m)Tc-doxorubicin could provide information on the response of tumours to doxorubicin.

Use of 99mTc-doxorubicin scintigraphy in females with breast cancer: a pilot study.

OBJECTIVE:: Doxorubicin (Eurofarma, São Paulo, Brazil) is an antitumour agent widely used in the treatment of breast cancer and can be used for tumour tracking when labelled with a radionuclide. Here, we present the results obtained with technetium-99m (99mTc)-doxorubicin, using the direct method, to evaluate its uptake in breast cancer. METHODS:: Four females with confirmed breast carcinoma diagnosis and breast image reporting and data system Category 5 on mammography underwent whole-body and thorax single-photon emission CT/CT imaging 1 and 3 h after 99mTc-doxorubicin administration. RESULTS:: We observed increased uptake in breast carcinoma lesions and elimination via renal and hepatic pathways. CONCLUSION:: These preliminary results suggest that 99mTc-doxorubicin may be a promising radiopharmaceutical for the evaluation of patients with breast cancer. Further studies are ongoing. ADVANCES IN KNOWLEDGE:: To our knowledge, this is the first study to evaluate the use of a directly labelled doxorubicin tracer in humans. 99mTc-doxorubicin could provide information on the response of tumours to doxorubicin.

Effect of different anticoagulants on the labelling of red blood cells and plasma proteins with 99Tcm.

There are controversies about the effect of different anticoagulants on the labelling of blood elements with 99Tcm. Our results show that the type of anticoagulant employed to withdraw the whole blood can modify the 99Tcm labelling of red blood cells (RBC) and plasma proteins (PP). The anticoagulants ACD (citric acid, sodium citrate and dextrose solution), heparin and sodium oxalate present similar results for the 99Tcm labelling of RBC with the exception of 0.13 microM stannous chloride. In this assay oxalate provides the best RBC labelling. In addition, with ethylenediaminetetraacetic acid (EDTA) the labelling of RBC is almost always lower than with the other anticoagulants, probably due to its high chelating capacity. The anticoagulants ACD, oxalate and heparin show the same results as expected with 99Tcm labelling of PP. The lowest labelling at 13.00 microM stannous chloride in the presence of oxalate is probably due to its low chelating capacity. The results also reinforce the idea that the erythrocyte membrane exerts an important role in the regulation of stannous ion transport into RBCs.

Preliminary observation of 99mTc-thymine imaging in breast neoplasms.

New biological knowledge and new diagnostic tools for breast cancer diagnosis may have an important impact on the strategies followed by oncologists in breast cancer management. So far, it has not been possible to label a nucleotide or its precursor with technetium-99m (99mTc) for use in in vivo studies. In this paper, we report the labelling of a precursor, the nitrogenate base thymine, with 99mTc. It has been used to evaluate breast lesions. After animal studies and with the consent of patients, it was employed for evaluation in humans. Thirty-nine women were studied: 32 patients and seven healthy volunteers. Twenty-three malignant lesions showed uptake of labelled thymine. Of the 12 benign cases, there was one false-positive uptake. Labelled thymine was also taken up by one case of malignant microcalcifications. Labelled thymine can be used as a diagnostic method in the identification of malignant anatomo-radiologic palpable lesions of the breast, observed by mammography, possibly avoiding unnecessary biopsies.

Comparison of Tc-99m THY and Tc-99m MIBI scans for diagnosis of breast lesions.

Mammoscintigraphy has recently become a useful method for breast cancer diagnosis, mainly in patients whose X-ray mammography is affected by technical problems. Tc-99m MIBI has been used for this purpose. A noninvasive, improved technique to select those who would most benefit from biopsy of the breast and reduce the number of negative biopsies is clearly of value and still desired. Here, we describe the use of Tc-99m THY in breast carcinoma and show the comparative results with Tc-99m MIBI in 29 patients. We studied a total of 39 women, 32 were patients and 7 healthy volunteers. Of the 32 patients, 3 had bilateral pathology. In addition, mammography imaging and histopathologic findings were presented. Twenty three malignant lesions were taken up by labeled thymine. Of the 12 benign cases there was one false-positive uptake with Tc-99m THY. There was no thymine uptake in the breasts of the healthy volunteers. Of the 30 cases treated with both radiopharmaceuticals there were 4 false-positives and 1 false-negative uptake with Tc-99m MIBI. The results confirm that Tc-99m THY breast imaging has a high specificity of 94.73% (18/19), an accuracy of 97.61% (41/42) and a positive predictive value of 95.83% (23/24) when compared with Tc-99m MIBI specificity of 71.42% (10/14), an accuracy of 86.48% (32/37) and a positive predictive value of 84.61% (22/26) in detection of breast carcinoma. Scintimammography using Tc-99m THY could influence the therapeutic strategy and reduce the number of mammographically recommended surgical biopsies that yield benign results.

Esophageal reconstruction surgery in oncologic patients: determination of gastric emptying time.

All parts of the gastrointestinal tract are accessible for study using nuclear medicine techniques. We have studied the effect of esophageal reconstruction surgery, in different periods of time, after surgical procedure. Oncologic patients (19) were evaluated after esophageal reconstruction surgery with gastric (group II - 14 patients) or colonic tube (group III - 5 patients) and they were compared with 15 healthy volunteers (group I). Gastric emptying was performed in the same subjects using solid food (egg sandwich) labeled with 99mTc-phytate. In emptying gastric studies, the mean (T1/2) of the patients was much faster than those of the control (p<0.05) when 1/3 distal tube was considered as stomach. However, there was no difference between the T1/2 of group II and group III. We concluded that this nuclear medicine method could be useful in the monitoring the surgical reconstruction of the esophagus.

Influence of tobacco on the labelling of red blood cells and plasma proteins with technetium-99m.

Technetium-99m-labelled red blood cells (RBC) have been used as radiopharmaceutical in nuclear medicine. The influence of drug interaction in this labelling process has been described along with the biological effects of tobacco on the labelling of blood elements with technetium-99m. The labelling of RBC and plasma proteins can be decreased in presence of tobacco. This can be due to either a direct or indirect effect (reactive oxygen species) of tobacco by (i) oxidation of the stannous ion, (ii) possible damages caused in plasma membrane and/or (iii) possible chelating action on the stannous and/or pertechnetate ions.

Identification of sentinel node in breast cancer.

Axillary lymphadenectomy is a very important procedure in the staging of breast cancer patients. However, it is associated with a significant morbidity rate. On the other hand, using early diagnosis we can see a high number of cases where the lymph nodes are negatives. With the intention of avoiding unnecessary axillary dissection, the possibility of evaluating a single node has been studied. This lymph node, defined as "sentinel node", would be the first to receive tumoral lymphatic drainage. The aim of this study is to evaluate: (i) the efficacy of the methods to identify the sentinel nodes, (ii) estimate the predictability of the histological examination of the sentinel node in comparison to other nodes of the axilla, (iii) compare the efficacy of the frozen section regarding the definitive histological examination of the same node. This study was performed in 29 patients, and the sentinel node was identified in all of them. It was metastatic in 7 (24.1%). Out of the 22 patients where the node was negative, 15 were submitted to complete dissection. Out of these 15, there was one case (6.7%) where one lymph node of the first level was positive. All 7 patients with the positive sentinel node were submitted to axillary dissection. When comparing the histological examination of the sentinel node with other nodes, we got a sensitivity of 87.5%, specificity of 100%, predictive positive value of 100%, predictive negative value of 93% and efficacy of 95%. The intra-operative examination was made in 24/29 cases (82.7%). The correlation between both examinations was 95.8%. This study shows that the technique of the sentinel node will be a reliable method to avoid radical axillary dissection in breast cancer patients with early diagnosis.

Identification of sentinel node in breast cancer: comparison between peritumoral and periareolar injection of the radiopharmaceutical contrast medium.

Axillary node status is the most important prognostic factor for patients with primary breast carcinoma. The sentinel node biopsy (SN) technique has received much attention as a possible alternative to axillary lymph node dissection. The aim of this study is to identify the sentinel node by periareolar and subdermal injection of the radiopharmaceutical in four points, independent of tumor topography and the presence of biopsies and/or previous surgery. The peritumoral injection technique was carried out for comparison purposes. This study was performed on 115 patients, divided into 2 groups: Group A (25 patients, peritumoral injection) and Group B (90 patients, injection in four points). All the SN biopsies were studied by both imprint cytology and H&E staining. Control axillary lymph-node dissection was followed in all patients from Group A and in these positive cases from Group B. Twenty-two out of the twenty-five (88%) SNs were identified in Group A. There was no false negative; the sensitivity and specificity were 100%. Eighty-two of the ninety (91.1%) SNs were identified in Group B. Lymphoscintigraphy showed radiopharmaceutical migration to axilla in 93.7% of the cases. Hotspot area was 10 to 100 times the intensity of the background radiation. Among the 92 cases with negative sentinel nodes at intraoperative examination (TP), the SN histopathology confirmed the absence of cancer cells in 89 patients, whereas 3 were positive for metastatic cells. This study shows that periareolar injection in four points seems to be a good lymphatic mapping method for SN identification. We suggest standardizing this site of injection to identify the SNs. More studies to confirm these findings are ongoing.

Effect of a chemotherapeutic drug on the biodistribution of 99mTc-DTPA in Balb/c mice.

The biodistribution of radiotracers used in diagnostic imaging can be grossly and recognizably altered by a wide variety of drugs and other treatment modalities, such as surgery and radiotherapy. Knowledge of such altered biodistribution is important both in making diagnostic inferences from scans and in dosimetric considerations. Vincristine is a drug that has been used as a component of many chemotherapeutic regimens because of its relative lack of hematologic toxicity. Its mechanism of action is by interfering with microtubule formation. The metabolic fate of vincristine has not been clearly determined and apparently undergoes in vivo decomposition. We have studied the effect of vincristine on the biodistribution of the 99mTc-DTPA. Vincristine was administered by ocular plexus via into female isogenic Balb/c mice. One hour after the last dose, 99mTc-DTPA (7.4 MBq) was injected and after 0.5 hour the animals were rapidly sacrificed. The organs were isolated, the radioactivity uptakes determined in a well counter and the percentages of radioactivity (% rad) in the organs calculated. The results have shown that the percentage rad has not been significantly altered in pancreas, thyroid and brain whilst a significant increased in thymus, ovary, uterus, spleen, kidney, heart, stomach, lung, liver and bone was reported. The results could be explained by the metabolization and/or therapeutic and immunosuppressive action of vincristine.

Effect of cyclophosphamide on the binding of 99mTcO-4 and 99mTc-MDP to blood cells and plasma proteins.

Since the introduction of technetium-99m (99mTc) and its rapid acceptance as a tool in nuclear medicine, very little information is available about its biological action as 99mTc-radiopharmaceuticals. We have determined if cyclophosphamide, an alkylating agent, used in oncology as a chemotherapeutic drug, modifies the binding of 99mTcO-4 and 99mTc-MDP (99mTc-methylenediphosphonic acid) to blood cells and to plasma proteins. The radiopharmaceuticals were injected intravenously (iv) into SW-55 mice (male and female, weight 25 g) and samples of plasma and blood cells were separated. Cyclophosphamide (50 micrograms) was injected iv 1 h before the radiopharmaceuticals. Samples of plasma and blood cells were also precipitated with 5% trichloroacetic acid and soluble and insoluble fractions were isolated. The following results were obtained: 1) cyclophosphamide did not alter (0.25 to 8 h) percent radioactivity of 99mTcO-4 in plasma or blood cells but increased the binding of 99mTc-MDP to blood cells; 2) cyclophosphamide did not alter (0.25 to 8 h) the binding of 99mTcO-4 in insoluble fraction of plasma and decreased (1 to 4 h) percent radioactivity of 99mTc-MDP in the insoluble fraction of plasma; 3) cyclophosphamide increased (0.25 to 4 h) percent radioactivity of 99mTcO-4 in the insoluble fraction of blood cells but did not alter the binding of 99mTc-MDP. Cyclophosphamide and/or its metabolites modified the effective half-life of these radiopharmaceuticals (to 99mTcO-4 was increased 2.3 to 3.4 h and to 99mTc-MDP was decreased 3.3 to 2.1 h) and possibly increased the permeability of blood cells to 99mTcO-4.

In vitro effect of cyclophosphamide on the binding of radiopharmaceuticals (99mTcO4- and 99mTc-MDP) to blood elements.

Sodium pertechnetate (99mTcO4-) and many 99mTc-products are the radiopharmaceuticals most frequently used in nuclear medicine. Using an in vitro model, we evaluated the effect of cyclophosphamide on percent radioactivity of 99mTcO4- and methylenediphosphonic acid (99mTc-MDP) bound to isolated blood elements. Blood samples were incubated with the two radiopharmaceuticals, plasma and blood cells were separated and precipitated, and soluble and insoluble fractions were separated. To evaluate the effect of cyclophosphamide, blood was incubated with this drug 1 h prior to the addition of the radiopharmaceuticals. The fraction of 99mTcO4- radioactivity was slightly higher in plasma (61.2 to 53.8%) than in blood cells (38.8 to 46.2%) up to 6 h and cyclophosphamide did not interfere with this distribution. The amount of 99mTc-MDP radioactivity was higher in plasma (91.1 to 87.2%) than in blood cells (8.9 to 12.8%) up to 24 h and cyclophosphamide did not modify it. The binding of 99mTcO4- to the insoluble fraction of plasma (4.9 to 6.1%) was low and cyclophosphamide did not interfere with it up to 6 h, but a small blockade (9.8 to 4.8%) was observed at 24 h. From 3 h on, cyclophosphamide slightly inhibited 99mTcO4- binding to blood cells (23.1 to 16.6%) and increased it at 24 h (31.2 to 14.3%). Cyclophosphamide did not alter 99mTc-MDP binding to the insoluble fraction of blood cells and slightly decreased 99mTc-MDP binding to the insoluble fraction of plasma (29.8 to 23.6%) up to 6 h.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro radioautographic studies of the biodistribution of radiopharmaceuticals on blood elements.

In the present study we evaluated the binding of the radiopharmaceuticals sodium pertechnetate (Na 99mTcO4), methylenediphosphonic acid (99mTc-MDP) and glucoheptonate acid (99mTc-GHA) to blood elements using centrifugation and radioautographic techniques. Heparinized blood was incubated with the labelled compounds for 0, 1, 2, 3, 4, 6 and 24 h. Plasma (P) and blood cells (BC) were isolated and precipitated with 5% trichloroacetic acid (TCA), and soluble (SF) and insoluble fractions (IF) were separated. Blood samples were prepared (0 and 24 h) and coated with LM-1 radioautographic emulsions and percent radioactivity (%rad) in P and BC was determined. The binding of Na 99mTcO4 (%rad) to P was 61.2% (0 h) and 46.0% (24 h), and radioautography showed 63.7% (0 h) and 43.3% (24 h). The binding to BC was 38.8% (0 h) and 54.0% (24 h), and radioautography showed 36.3% (0 h) and 56.7% (24 h). 99mTc-MDP study presented 91.1% (0 h) to P and 87.2% (24 h), and radioautography showed 67.9% (0 h) and 67.4% (24 h). The binding to BC was 8.9% (0 h) and 12.8% (24 h), and radioautography showed 32.1% (0 h) and 32.6% (24 h). 99mTc-GHA study was 90.1% (0 h) to P and 79.9% (24 h), and radioautography showed 67.2% (0 h) and 60.1% (24 h). The binding to BC was 9.9% (0 h) and 20.1% (24 h), and radioautography showed 32.8% (0 h) and 39.9% (24 h). The comparison of the obtained results suggests that the binding to plasma and blood cells in the two techniques used (radioautography and centrifugation) is qualitatively in accordance.