Scintigraphic Localization Research Articles

Feasibility of iodine-125 labeled anti-human hemoglobin antibody in the detection of bleeding sites from the large bowel-A preliminary study.

A monoclonal anti-human hemoglobin antibody that cross-reacts with mouse hemoglobin was labeled with Iodine-125 through the Chloramine-T method. The labeled antibody was used in an attempt to recognize bleeding sites from the large bowel in a mouse model, through a non-invasive enema-like study. In vitro experiments after double column chromatography of the labeled antibody and 10% trichloroacetic acid conjugation revealed that about 80% of the radioactivity was incorporated into protein. Inhibition assay containing cold (non-radiolabeled) antibody showed that Iodine-125 radiolabeled antibody preserved its immunoreactivity. Autoradiographs exquisitely demonstrated accumulation of isotope in the corresponding intestinal bleeding areas. These findings suggest that this method can be useful for scintigraphic localization of bleeding sites in the large bowel.

Detecting the sentinel lymph node in patients with differentiated thyroid carcinoma.

The aim of this study was to evaluate sentinel lymph node mapping in patients with differentiated thyroid carcinoma. Nine patients with suspected thyroid carcinoma who were scheduled to undergo thyroidectomy underwent scintigraphic localization of sentinel lymph nodes (SLNs). On the day of surgery we injected 37 MBq technetium-99m nanocolloid intratumourally. Dynamic data up to 10 min followed by planar anterior and lateral oblique images up to 1 h after tracer administration were recorded. At surgery the primary tumour was excised first, then the SLNs were removed using a gamma probe. Four patients had papillary carcinoma, two follicular carcinoma, one an oncocytic tumour and two benign tumours. An SLN was identified in all four patients with papillary carcinoma. In the two patients with follicular carcinoma, SLN detection failed. Five patients had one radioactive node, one had three and one had four. In one patient, no SLN was visible with scintigraphic imaging but at surgery three SLNs could be clearly identified using the gamma probe after removal of the primary tumour. There were no false-negative findings. This initial study indicates that in patients with papillary thyroid carcinoma detection of the SLN is possible, whereas the technique failed in two patients with follicular carcinoma. A study on a larger patient sample is now warranted.

Improved detection of gastrointestinal bleeding sites with 99mTc market autologous erythrocytes and continuous dynamic scintigraphy with cine-mode display

Scintigraphic studies of gastrointestinal bleeding are usually performed in static acquisition mode and without continuous imaging over a longer period. The aim of this study was to evaluate the diagnostic accuracy of continuous dynamic 99mTc red blood cell scintigraphy (BQS) and cine-mode display in the assessment of unexplained gastrointestinal bleeding. We performed BQS in 40 patients (mean age 57 years) with gastrointestinal bleeding from an undetermined source. All these patients had negative findings of previous examinations. Blood transfusions were required in 16 patients. Continuous dynamic scintigraphic acquisition was performed up to 6 h post injection (p.i.). The scintigraphic data were reviewed without knowledge of the patient's final diagnosis. For this purpose we used a cine-mode display. Dynamic 99mTc red blood cell scintigraphy correctly identified the site of active bleeding in 22 of 23 patients with positive scintigraphic findings. The sensitivity of the scan was 95%, the specificity 94%, the positive and negative predictive values 95% and 94%, respectively. Forty-three percent of the scans became positive within 1.5 h and 82% within 5 h. Positive scans were more likely in patients who required blood transfusions than in patients without transfusion requirement (16 vs 7 patients), and the bleeding site was identified earlier in the former group (mean 2.83 vs 5.28 h p.i.). The scintigraphic identification of the bleeding lesions enabled the performance of a more limited surgical approach in the colon as well as in the distal small intestine, while exact scintigraphic localization was not possible if the bleeding site was located in the proximal small intestine. Continuous dynamic 99mTc red blood cell scintigraphy interpreted by cine-mode display is highly accurate in the identification of a bleeding site. When performed correctly, scintigraphy enables usually segmental resection of these lesions.

Sentinel lymph node mapping for breast cancer: analysis in a diverse patient group.

To evaluate sentinel lymph node mapping in patients with breast cancer. Sixty-two patients with breast cancer scheduled to undergo axillary nodal dissection underwent scintigraphic localization of sentinel lymph nodes with filtered technetium 99m sulfur colloid. At surgery, isosulfan blue was injected. Sentinel nodes were identifiable by blue color and by radioactivity with hand-held gamma probe. Results were analyzed statistically. A sentinel lymph node was identified in 49 patients (79%). Lymph nodes were positive for metastatic disease in 26 patients (42%). The mapping success rate was 78% (n = 21) in the 27 patients with no prior surgery, 78% (n = 18) in the 23 patients with prior surgery, and 86% (n = 12) in the 14 patients with prior chemotherapy. Axillary nodes were positive in 11 (41%) of the 27 patients with no prior intervention, six (26%) of the 23 patients with prior surgery, and 10 (71%) of the 14 patients with prior chemotherapy. There were no false-negative findings in patients without prior intervention. Four patients with positive nodes had false-negative sentinel nodes. Sentinel lymph node mapping and biopsy without axillary dissection is appropriate in patients with breast cancer who have not undergone prior intervention. Further study is necessary to ascertain the accuracy of the procedure for patients who have undergone presurgical chemotherapy or previous excisional biopsy.

Invited commentary to: „Scintigraphic and intraoperative scintimetric localization of an ectopic parathyroid adenoma with Tc-99m Tetrofosmin and Tc-99m Sestamibi“

Invited commentary to: „Scintigraphic and intraoperative scintimetric localization of an ectopic parathyroid adenoma with Tc-99m Tetrofosmin and Tc-99m Sestamibi“

Invited commentary to: „Scintigraphic and intraoperative localization of an ectopic parathyroid adenoma with Tc-99m Tetrofosmin and Tc-99m Sestamibi“

Invited commentary to: „Scintigraphic and intraoperative localization of an ectopic parathyroid adenoma with Tc-99m Tetrofosmin and Tc-99m Sestamibi“

Invited commentary to: „Scintigraphic and inoperative scintimetric localization of an ectopic parathyroid adenoma with Tc-99m Tetrofosmin and Tc-99m Sestamibi“

Invited commentary to: „Scintigraphic and inoperative scintimetric localization of an ectopic parathyroid adenoma with Tc-99m Tetrofosmin and Tc-99m Sestamibi“

Intraoperative Scintigraphic Detection of Abdominal Endocrine Tumors

Surgery of endocrine tumors benefit from accurate pre and- intraoperative localization methods,and scintigraphy has become an important contribution in this respect. In the present thesis therequisites for scintigraphic localization of abdominal endocrine tumors and new detectors forintraoperative gammadetection are evaluated.Ac5 is a monoclonal murine antibody developed against human adrenocortical carcinoma. In a nude mouse experimental model, the radiolabeled antibody and its Fab´2 fragment were evaluated after grafting of two human adrenocortical carcinoma cell-lines (SW 13, T-CAR1). During scintigraphy of grafted animals, tumors were visualized especially with the fragmented antibody. The Ac5 antibody/Fab2 fragment may become a diagnostic tool for detection of adrenocortical carcinoma.The somatostatin analogue [111In]-DTPA-D-[Phe1]-octreotide (OctreoScan®) has been shown to visualize endocrine tumors with scintigraphy. The biodistribution of [111In]-DTPA-D-[phe1]-octreotide was studied by use of operative biopsies. Mid-gut carcinoids and endocrine pancreatic tumors of patients exposed to [111In]-DTPA-D-[Phe1]-octreotide, revealed high uptake in tumors with a tumor-to-blood ratio up to 2000. After preoperative single photon emission computerized tomography (SPECT), commercially available hand-held gammasensitive probes were used for intraoperative detection of tumors. These detectors were found to be insufficient in the abdomen mainly because of poor adaptation to the high background activity of 111In. A novel detector, H-probe2 was constructed. It was found to detect even tiny tumors, lesions inaccessible to surgical palpation upon ex vivo scanning of operative specimens. In vivo, H-probe2 detected smaller tumors than preoperative SPECT, but the scanning procedure was too time consuming for surgical applicability. Further development resulted in Matris 16, a computerized 16 channel detector for intraoperative use in combination with [111In]-DTPA-D-[Phe1]-octreotide. Matris 16 demonstratedsubstantial sensitivity and spatial resolution. It had the ability to detect abdominal endocrine tumorsmeasuring down to a few mm both in vivo and ex vivo. By allowing faster scanning with preserved sensitivity Matris 16 can improve the intraoperative tumor detection of endocrine neoplasms.

Scintigraphy and biodistribution of monoclonal adrenocortical antibody in mice grafted with human adrenocortical carcinoma

A murine monoclonal antibody recognizing normal and neoplastic human adrenocortical cells has been evaluated for scintigraphic localization and biodistribution in 53 nude mice grafted subcutaneously with human adrenocortical cell lines SW-13 and T-CAR 1. The immunoglobulin G1 antibody and its Fab'2 fragment were purified and labeled with 125I. The tumor grafts exhibited diameters of 5 to 15 mm at 4 to 6 weeks after transplantation, when mice received a single subcutaneous or intraperitoneal injection of 50 micrograms iodinated intact or fragmented antibody, respectively. Examination up to 8 days after immunoglobulin G administration showed mean radioactivity ratios less than 1.0 for tumor to blood and corresponding ratios in tumor to lung, liver, spleen, and kidney from 0.6 to 5.3 at the time of peak tumor to blood ratio. A high background activity was noted on scintigraphic tumor visualization with the iodinated immunoglobulin G. In contrast, the radiolabeled Fab'2 fragment displayed gradually rising tumor to blood ratios, which, 4 days after injection, averaged 10.5 for T-CAR1 and 5.3 for SW-13. Tumor transplants were scintigraphically visualized without substantial background activity 3 days after Fab'2 injection, when the ratio of radioactivity in the tumor to the investigated murine organs was 0.5 to 7.3. The findings substantiate that immunoscintigraphy with the Fab'2 fragment of the antiadrenocortical Ac5 antibody may become a tool to localize human adrenocortical carcinoma.

Combined use of 111In-labeled pentetreotide and three-step immunoscintigraphy with antichromogranin A monoclonal antibody in the diagnosis of pituitary adenomas.

For various pituitary adenomas, it has been demonstrated that somatostatin receptor can be present. Pilot studies have shown that radio-indium labeled pentetreotide allows very good scintigraphic localization of somatostatin receptor-bearing cell masses. Recently, the presence of CgA in pituitary adenomas has also been demonstrated. MAb A11, raised against CgA, has been successfully used with a three-step ISG for the diagnosis of neuroendocrine tumors. Therefore the combined use of three-step ISG with MAb A11 and radiolabeled somatostatin can be useful in the diagnosis of pituitary adenomas. Twelve patients, 5 secreting (group A) and 7 nonsecreting (group B) pituitary adenomas, were enrolled in the study. All patients underwent three-step ISG, and, 2 wk later, scintigraphy with 111In-labeled pentetreotide (Octreoscan). Three-step ISG consisted of i.v. injection of 1 mg of biotinylated MAb A11 (first step), followed by 10 mg of avidin (second step) and [99mTc]PnAO-biotin (third step). Tomographic imaging were acquired for three-step ISG and Octreoscan at 2 and 4 h after radiotracer injection, respectively. The results are the following: 2 patients of group A (secreting tumors) had a positive three-step ISG, whereas all the patients but one of the same group had a positive pentetreotide study; all the patients of group B (nonsecreting tumors) had a positive three-step ISG and 4 had a positive pentetreotide scintigraphy. These data suggest the utility of the combined use of these techniques for a better diagnosis of pituitary adenomas.

In vitro autoradiographic and in vivo scintigraphic localization of somatostatin receptors in human lymphatic tissue

Receptors for the neuropeptide somatostatin (SS) were evaluated in vitro and in vivo in various human lymphatic tissues, ie, thymus, spleen, and lymph nodes; thymic carcinoids and thymomas were also tested. The receptors were measured in vitro using receptor autoradiography on tissue sections incubated with the SS analog 125I- [Tyr3]-octreotide or 125I-[Leu8,D-Trp22,Tyr25]-SS-28. All tissues were SS-receptor positive for either radioligand, except the thymomas. In thymic tissue, the receptors were diffusely located in the medulla, presumably on epithelial cells. In the spleen, the red pulp was strongly labeled. In the lymph nodes, the germinal centers were preferentially labeled. In all tissues, the receptors were of high affinity (kd thymus, 0.84 nmol/L; kd spleen, 1.6 nmol/L; kd lymph node, 0.62 nmol/L) and specific for SS. Displacement by nanomolar concentrations of SS-14, SS-28, and octreotide was observed, as was guanosine triphosphate dependency. The in vivo visualization of somatostatin receptors was performed after injection of 111In-DTPA- octreotide and gamma-camera scintigraphy. The spleen, but not thymus or lymph nodes, were visualized. These data suggest an important role for SS in regulating immune functions through SS receptors in thymus, spleen, and lymph nodes. Furthermore, SS may regulate neuroendocrine functions in the thymus.

In Vitro Autoradiographic and In Vivo Scintigraphic Localization of Somatostatin Receptors in Human Lymphatic Tissue

Receptors for the neuropeptide somatostatin (SS) were evaluated in vitro and in vivo in various human lymphatic tissues, ie, thymus, spleen, and lymph nodes; thymic carcinoids and thymomas were also tested. The receptors were measured in vitro using receptor autoradiography on tissue sections incubated with the SS analog 125I-[Tyr3]-octreotide or 125I-[Leu8,D-Trp22,Tyr25]-SS-28. All tissues were SS-receptor positive for either radioligand, except the thymomas. In thymic tissue, the receptors were diffusely located in the medulla, presumably on epithelial cells. In the spleen, the red pulp was strongly labeled. In the lymph nodes, the germinal centers were preferentially labeled. In all tissues, the receptors were of high affinity (kd thymus, 0.84 nmol/L; kd spleen, 1.6 nmol/L; kd lymph node, 0.62 nmol/L) and specific for SS. Displacement by nanomolar concentrations of SS-14, SS-28, and octreotide was observed, as was guanosine triphosphate dependency. The in vivo visualization of somatostatin receptors was performed after injection of 111In-DTPA-octreotide and gamma-camera scintigraphy. The spleen, but not thymus or lymph nodes, were visualized. These data suggest an important role for SS in regulating immune functions through SS receptors in thymus, spleen, and lymph nodes. Furthermore, SS may regulate neuroendocrine functions in the thymus.

Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients.

Various tumours, classically specified as either neuroendocrine or non-neuroendocrine, contain high numbers of somatostatin receptors, which enable in vivo localization of the primary tumour and its metastases by scintigraphy with the radiolabelled somatostatin analogue octreotide. In addition granulomas and autoimmune processes can be visualized because of local accumulation of somatostatin receptor-positive activated mononuclear leucocytes. In many instances a positive scintigram predicts a favourable response to treatment with octreotide. It is tempting to speculate that octreotide labelled with an appropriate radionuclide might be used in cancer therapy. The successful application of radiolabelled octreotide in scintigraphy indicates the possible usefulness of other radiolabelled peptides, either native peptides or derivatives of these, in, for example, nuclear oncology. The small size of these peptides, e.g. bombesin and substance P, is of the utmost importance for a relatively fast blood clearance, thus leading to low background radioactivity. In this way peptides are powerful alternatives to (fragments of) monoclonal antibodies, the application of which to scintigraphic localization of specific cell surface antigen-bearing tumours is plagued by slow blood clearance and, hence, high background levels.

Tc-99m albumin scintigraphy in the localization of protein loss in the gut.

Scintigraphic localization of gastrointestinal protein loss has been recently reported. A noninvasive method for the localization of protein loss in the gut using Tc-99m labeled albumin seems encouraging and is described here. In six patients studied for protein-losing enteropathy, scintigraphic results of four were positive.

Labelling of leukocytes with 99mTc-HMPAO for scintigraphy of inflammatory lesions and abscesses

A simplified and efficient procedure for 99mTc-HMPAO-labelling of leukocytes is described. For this purpose, the pH and concentration of the 99mTc-HMPAO preparation was modified. Leukocytes were isolated from a 20 mL mixture of patient blood, 5 mL ACD and 0.8 mL methylcellulose after 1 h sedimentation of erythrocytes and centrifugation (at 400 g) of the obtained plasma layer. Simultaneously, 99mTc-HMPAO was prepared (one single-dose kit for two patients) by adding 2.2 mL 99mTc-generator eluate and, after 10 min, 0.3 mL of phosphate buffer to lower the pH to 7. The isolated WBCs were then labelled by the addition of 1-1.2 mL of 99mTc-HMPAO solution and incubated for 20 min. The unbound tracer was then discarded, the labelled WBC washed and finally resuspended in autologous cell-free plasma. Leukocytes labelled by this procedure were used for scintigraphic localization of inflammatory lesions and abscesses in the gastro-intestinal tract. The labelling efficiency was 60 ± 9%, with a separation yield of 55 ± 11%.

Scintigraphic localization of ectopic parathyroid lesions with thallium‐201

Six consecutive patients with ectopic parathyroid lesions were studied by preoperative thallium-technetium scintigraphy. Ectopic lesions were accurately localized in 5 of 6 patients. Four of five lesions deep in the superior mediastinum, and 1 in the superior carotid sheath, were correctly identified. Ectopic lesions in 4 of 5 patients, who had previously undergone unsuccessful exploration, were correctly localized. In 1 previously unoperated patient, a mediastinal lesion was identified by preoperative scintigraphy. In 2 patients, deep mediastinal exploration via manubriotomy was successfully conducted without confirmation by "invasive" intravascular procedures. There were no false-positive studies. Lesions identified weighed from 185 mg to 9 g and were from 1.1 to 3.0 cm in size. Scintigraphy is particularly effective for demonstration of ectopic parathyroid tissue, because the absence of thyroid tissue in the mediastinum or superior cervical region permits appreciation of areas of abnormal thallium uptake unobscured by uptake in adjacent thyroid tissue. We conclude that ectopic parathyroid tissue may be accurately identified by thallium-technetium scintigraphy without confirmation by invasive intravascular studies.

Scintigraphic Localization of a Bleeding Leiomyosarcoma of the Proximal Jejunum

We report a case of scintigraphic detection and localization of a bleeding leiomyosarcoma of the jejunum utilizing Tc-99m labeled red blood cells. Despite conflicting mesenteric arteriograms, the patient underwent surgery based upon the scintigraphic study, resulting in a successful outcome.

Rapid preparation of 123I-labelled methylene blue and toluidine blue

Methylene blue and toluidine blue are phenothiazinium dyes used to localize parathyroid glands visually during surgery. For the purpose of assessing the potential of radiolabelled analogues for scintigraphic localization of parathyroids, a rapid and convenient method has been developed for covalently labelling the dyes with iodine-123. Treatment of aqueous methylene blue or toluidine blue with 123I-sodium iodide in the presence of potassium iodate and hydrochloric acid at 100 degrees C for 1 h results in incorporation of 80-90% of the radioiodine into the dye. The chemical and radiochemical impurities are readily removed by passage through a disposable sample preparation column. Using the optimized protocol, a sterile, pyrogen-free multi-dose solution of radioiodinated dye (pH 7, specific activity greater than or equal to 37 MBq mg-1, radioactivity concentration congruent to 37 MBq ml-1, radiochemical purity greater than 99%, overall activity yield available for injection 60-70%) can be prepared within 1.5 h.

Radioiodinated benzodiazepines: agents for mapping glial tumors.

Two isomeric iodinated analogues of the peripheral benzodiazepine binding site (PBS) ligand Ro5-4864 have been synthesized and labeled in high specific activity with iodine-125. Competitive binding assays conducted with the unlabeled analogues indicate high affinity for PBS. Tissue biodistribution studies in rats with these 125I-labeled ligands indicate high uptake of radioactivity in the adrenals, heart, and kidney--tissues known to have high concentrations of PBS. Preadministration of the potent PBS antagonist PK 11195 blocked in vivo uptake in adrenal tissue by over 75%, but to a lesser degree in other normal tissues. In vivo binding autoradiography in brain conducted in C6 glioma bearing rats showed dense, PBS-mediated accumulation of radioactivity in the tumor. Ligand 6 labeled with 123I may have potential for scintigraphic localization of intracranial glioma.

A simple method of granulocyte enrichment of crude white cell suspensions labelled with 111In.

A simple method of granulocyte enrichment of a 111In-labelled mixed white cell suspension is described. The method rests on preferential sedimentation by gravity of the granulocytes during labelling. In the 50 studies performed, the granulocytes constituted on average 90% of the 111In-labelled white cells injected for abscess detection. The modest degree of artefactual granulocyte pooling in the lungs and the results of the scintigraphic studies suggest that the method described is well-suited for scintigraphic localization of infectious and inflammatory processes.