A new radiocolloid for sentinel node detection in breast cancer.

BACKGROUND: The optimal radioactive tracer and technique for sentinel lymph node localization in breast cancer is yet to be determined. The dilemma of small particle size with dispersion to second echelon nodes versus failure of migration of larger radiocolloids needs to be resolved. A new radiocolloid preparation with particle size under 0.1 micron was developed with excellent primary/post lymphatic entrapment ratio. OBJECTIVE: To assess the feasibility of a new 99mTc radiocolloid cysteine-rhenium colloid in sentinel lymph node (SLN) localization for breast cancer. METHODS: Forty-seven patients with newly diagnosed T1 or T2 breast cancer underwent injection of 99mTc-labeled cysteine-rhenium colloid followed by lymphoscintigraphy. Same day SLN biopsy with patent blue dye and intraoperative gamma probe to identify SLNs were performed. RESULTS: SLN mapping and intraoperative localization were successful in 46/47 (98%) of patients. The blue dye radioactive tracer concordance was 94%. There was one false-negative in a patient with a nonpalpable tumor that underwent ultrasound-guided peritumoral radiocolloid injection. CONCLUSIONS: 99mTc-cysteine-rhenium colloid is highly effective in identifying SLNs. It has the advantage of smaller particle size than sulfur colloid with easier lymphatic migration. It has a more neutral pH with less pain on injection and does not require filtration, thereby minimizing radiation exposure to technologists.

Sentinel node biopsy in melanoma using technetium-99m rhenium colloid: the London experience.

Nodal metastases in patients with melanoma identify a reduction of survival by 50%; however, elective lymph node dissection (ELND) has not been shown clearly to improve survival. Morton's technique of sentinel node biopsy, using preoperative lymphoscintigraphy and intraoperative blue dye, addresses elegantly the controversy regarding ELND. Sentinel node biopsy has been shown to stage the patient accurately because metastases from melanoma follow an orderly progression from the sentinel node to the remainder of the basin. Fifty-six consecutive patients with American Joint Committee on Cancer stage 1b or 2 melanoma seen at the London Health Sciences Center between July 1998 and January 2000 were enrolled prospectively to undergo sentinel node biopsy. Preoperative lymphoscintigraphy was conducted in the nuclear medicine department. A total of 10 to 15 MBq (0.27-0.41 mCi) of technetium 99m (99mTc) rhenium colloid or filtered sulfur colloid was injected intradermally around the biopsy scar. Images were obtained to localize all draining nodal basins. The location of the sentinel node was marked on the skin. The patient was taken to the operating room and anesthetized. Isosulfan blue dye was injected intradermally around the biopsy scar. A hand-held gamma probe was used intraoperatively as a guide to the first draining node. Blue-stained lymphatic channels aided in the dissection. Sentinel node localization was successful in 55 of 56 patients, for an overall success rate of 98%. Preoperative lymphoscintigraphy identified a sentinel node in an unpredictable location in 32% of patients. On average, 2.3 sentinel nodes per patient were identified on the initial scan, and 2.2 sentinel nodes per patient were recovered at surgery. Both 99mTc rhenium and filtered sulfur colloid showed no substantial differences in tracer uptake and retention in the sentinel node. Twelve patients had a positive sentinel node on routine histology, and 11 patients subsequently underwent completion lymphadenectomy. The mean thickness of the primary melanoma in the 12 patients with positive sentinel nodes was 3.7 mm compared with a mean tumor thickness of 1.8 mm in the remaining 41 patients with negative biopsies (p = 0.0003). Two patients experienced recurrence in a regional basin after negative pathological evaluation of the sentinel node. Reverse transcription-polymerase chain reaction analysis of both of these patients was positive. Two patients are alive with metastatic disease and 54 patients are alive without disease, with a mean follow-up of 1 year (range, 2-24 months). Complications occurred at a substantially higher rate (45%) after completion lymphadenectomy than after sentinel node biopsy alone (9%). Sentinel node biopsy is a feasible technique with a high success rate (98%), but it requires a multidisciplinary approach. This study validates the clinical usefulness of 99mTc rhenium colloid for lymphoscintigraphy.

Pulmonary uptake of technetium-99m-sestamibi induced by dipyridamole-based stress or exercise.

UNLABELLED: On poststress images with 99mTc-sestamibi (MIBI), increased lung uptake of the radiotracer may reflect severe or multivessel coronary artery disease. METHODS: We measured pulmonary/myocardial ratios of MIBI at standardized times on immediate poststress acquisitions and on delayed tomographic acquisitions. In 1500 sequential patients referred for rest and stress myocardial tomography, ancillary planar images were obtained 4 min postinjection at peak stress with exercise, either alone (exercise, n = 674), or after intravenous dipyridamole (dipyridamole, n = 826). RESULTS: Based on 95% confidence limits in the angiographic normals, high values for immediate acquisitions were found in 17% of dipyridamole studies and 15% of exercise studies. High values for delayed acquisitions were found in 10% of dipyridamole studies and 9% of exercise studies. For both stress modes, increased values were related (p < 0.001) to ischemic perfusion defects for immediate images, to fixed defects for delayed images, and to ventricular dilation in both cases. By logistic regression analysis, body weight and history of infarction were also minor independent determinants (p < 0.01) of delayed acquisitions. In a subset of 250 cases with angiographic correlation (163 with dipyridamole; 87 with exercise), immediate lung uptake was highly correlated with ventricular dysfunction and with coronary stenoses (p < 0.0001). Relationships were similar to those in a historic control series imaged with 201TI. Values for delayed poststress images, and for corresponding rest images, showed strong relationships to ventricular dysfunction but not to stenosis severity. CONCLUSION: The relationships of immediate lung uptake to scintigraphic and angiographic disease patterns suggest its possible diagnostic use as an indicator of stress-induced ventricular decompensation.

An atlas of renography with Tc-99m sestamibi: comparison with Tc-99m DTPA.

Tc-99m sestamibil demonstrates considerable renal uptake followed by net urinary clearance similar to that of creatinine. The authors have previously shown that renograms could be obtained in cardiac patients by imaging during the rest injection of the perfusion agent. The present study shows correlating Tc-99m sestamibi and Tc-99m DTPA studies in hypertensive patients with a spectrum of findings, including aortic aneurysms, asymmetry due to renovascular disease, cysts, bilateral renal dysfunction, and horseshoe kidney. Tc-99m sestamibi images have persisting background activity in the liver and spleen, but show renal structure and function in adequate detail. Quantitative analysis confirms that Tc-99m sestamibi has higher renal uptake, but less excretion than Tc-99m DTPA. Review of these correlating studies suggests straightforward transfer of diagnostic expertise with standard renography to this new application.

Dynamic renal imaging with technetium-99m-sestamibi in hypertension: potential for assessment of renovascular disorders.

UNLABELLED: The myocardial perfusion agent, 99mTc-sestamibi (MIBI), offers the potential to combine renal and myocardial imaging because of high initial renal extraction and significant renal clearance. METHODS: Dynamic renal imaging was performed during rest MIBI injections in 3 normal subjects (NS) and 91 patients referred for cardiac assessment. Ten served as normal controls, and 81 were hypertensive. Renal activity of MIBI during the first transit, uptake and excretory phases of the study was quantified. These data were compared with the normal kinetics of 99mTc-diethylenetriaminepentaacetic acid (DTPA) in concurrent studies. RESULTS: With MIBI, clear definition of the kidneys was possible on all phases in most studies; occasionally, overlap with liver or spleen provided a minor problem. Renal MIBI activity reached levels 70% greater than DTPA during first transit and remained higher throughout the study; renal/background activity ratios were also higher on the MIBI study (p < 0.001). During the excretory phase with MIBI, hepatic and splenic activity did not decline, and gut activity increased. In NS, 40% of the total activity was excreted in the urine in 1 hr; urinary MIBI clearances approximated creatinine clearance. Asymmetry in initial renal uptake was seen in 14 of 81 hypertensive patients (17%); renal cysts and aortic dilatation could also be identified. CONCLUSION: These data suggest that ancillary renography during rest injection of MIBI could be a useful addition to the cardiovascular assessment of selected patients.

Biodegradation of distal shunt catheters.

In a review of pediatric and adult distal cerebrospinal fluid shunt failures, the distal catheters were found to have deteriorated to the point of malfunction in 7 individuals after intervals of over 7 years. All cases presented in the first two decades of life with a duration of symptoms ranging from 1 to 62 days. The mechanism of shunt failure was assessed by radionuclide shuntogram study and at surgery. Degradation of catheter material led to irregular attenuation and fracture of the catheter wall with diffuse leakage of radionuclide into surrounding tissues. The catheter length of most chronic duration following implant was inevitably affected. Radionuclide shuntogram study of the distal catheter clearly identified the nature of the problem by showing an irregular outline of the catheter lumen due to spread of radioactivity into the surrounding soft tissues. Occasionally, intense foci of activity were identified at single or multiple sites where the catheter wall was grossly attenuated or fractured, resulting in cessation of catheter flow further distally. The biodegradability of distal shunt catheters leading to malfunction must be considered when assessing a young individual with features of hydrocephalus and a chronically implanted catheter length. Radionuclide shuntogram study is a convenient means of assessing the problem.

Three-phase bone scintigraphy. Asymmetric patterns in the upper extremities of asymptomatic normals and reflex sympathetic dystrophy patients.

Three-phase Tc-99m MDP scans of 61 patients with asymptomatic upper extremities randomly mixed with 17 studies of patients previously diagnosed with reflex sympathetic dystrophy were blindly interpreted by three observers. Asymmetry in any of the phases was recorded and a final diagnostic impression made. Thirteen of 17 reflux sympathetic dystrophy studies were rated abnormal by at least two observers. Mild to striking asymmetry was occasionally seen in all three phases in asymptomatic upper extremities. Twenty of 61 asymptomatic patients (33%) were rated abnormal by at least one observer, and 5 of 61 studies (8%) were rated abnormal by all observers. Asymmetries in normal patients occurred more commonly in the earlier phases, while asymmetry in the delayed images was mild in all but one. Tightening the criteria to exclude mild asymmetry in delayed images resulted in unacceptably low sensitivity for reflex sympathetic dystrophy (29%). Interobserver variability was most prominent in the flow and immediate images. In the diagnosis of reflex sympathetic dystrophy a greater reliance should be placed on the delayed images, which in themselves have an overall sensitivity of 94%. It is important, however, to recognize that occasional mild and rare moderate asymmetries in even the delayed images of normal individuals result in an overall lower specificity of 77%.

Comparison of Tl-201 renal uptake with Tc-99m DTPA angiorenography in patients with hypertension. Measures of renal asymmetry.

Renal uptake of Tl-201 reflects renal perfusion and may have a role in defining renal asymmetry in patients with hypertension who are referred for myocardial scintigraphy. The authors compared two methods of quantitating differential renal uptake of Tl-201, with similar data obtained from the angiographic and renal uptake (RU) phases of Tc-99m DTPA scintigraphy in 35 patients with hypertension. For Tl-201, asymmetry in renal counts was quantitated based on a simple outline technique or on interpolative background subtraction of 5-minute posterior images. Inter-observer and intra-observer variability among duplicate measurements were lower for Tl-201, particularly with interpolative background subtraction, than for Tc-99m DTPA. Renal/background ratios were similar for Tl-201 and RU-phase Tc-99m DTPA images when considering liver, spleen, or inter-renal regions as background; however, paraspinal uptake was relatively higher with Tl-201 (P less than 0.01). Qualitatively, renal asymmetry scores with the two radiotracers agreed (r = 0.89, blinded readings by four observers), although asymmetry was more marked with Tl-201 (P = 0.06). Measurements with Tl-201 agreed with both phases of Tc-99m DTPA (r = 0.96 to 0.98), but interpolative background subtraction systematically yielded greater inter-renal asymmetry than RU (P less than 0.01), reflecting the qualitative impression. Thus, ancillary Tl-201 imaging reflects differences between the kidneys in a fashion similar but not identical to Tc-99m DTPA scintigraphy.

Differential renal uptake of 201Tl: requirements for acquisition, display and quantification.

Renal uptake of 201Tl may have a role in screening for renal asymmetry in hypertensive patients (HP) who are referred for myocardial scintigraphy. The qualitative aspects of digitized planar images, and quantified differential renal uptake (DRU) of 201Tl were rated by comparing a simple technique (S) for outlining each kidney with an interpolative background subtracted technique (IB). These parameters were assessed in an initial series of patients by varying the length of acquisition (from 1 to 5 min), delay in acquisition (from 10 to 210 min after injection), and image preparation (nine-point smoothing). Six blinded observers rated the quality of coded images. Image quality was improved (P less than 0.01) by increasing the length of acquisition to at least 2 min, by smoothing of the images and by imaging within 2 h of 201Tl injection. Variability in quantification of DRU was suboptimal with acquisition for only 1 min and was more adversely affected with S than with IB. Clinical application of the quantitative technique was assessed in 180 HP and 32 normotensive controls. With IB, the normal range for DRU was slightly greater than for S. The two techniques were comparable in identifying abnormal cases and found 21 +/- 3% (S) and 19 +/- 3% (IB) of HP as lying outside the normal 99% confidence interval. Both quantitative techniques showed excellent agreement with renal angiography (n = 24). Furthermore, preliminary experience with surface markers and with 180 degrees tomography suggests the potential for simultaneous correction for renal depth. These data justify the use of adjunctive renal imaging during myocardial scintigraphy with 201Tl.

Screening for a renovascular etiology in hypertensive patients undergoing myocardial scintigraphy: differential renal thallium-201 uptake.

In hypertensive patients with target organ damage the search for possible etiologic factors may be particularly relevant. To evaluate renal symmetry, differential renal uptake of thallium-201 was quantified on renal images at 30 mins to 3 h after tracer injection in 112 hypertensive patients undergoing myocardial perfusion scintigraphy for chest pain. In some patients, renal angiographic status was known at the time of thallium-201 scintigraphy (n = 10), or disease was highly suspected (failed angioplasty, n = 6); the remainder (n = 96) were 'screened' for renovascular disease by renal thallium-201 imaging; 32 normotensive patients with no history of renal disease served as controls. Validation of thallium-201 renal imaging was obtained in a total of 17 hypertensive patients who had correlating contrast angiography, confirming eight cases of unilateral or asymmetric bilateral renovascular disease. Renography with technetium-99m DTPA was performed in 28 patients; differential renal function according to this modality correlated well with differential renal uptake of thallium-201 (r = 0.98). Of the screened hypertensives, eight had marked asymmetry of differential renal uptake and eight had possibly significant asymmetry. Renal thallium-201 imaging provided the first evidence of asymmetric renal perfusion in four cases subsequently confirmed by abdominal angiography. In addition, four post angioplasty cases had persistent or progressive asymmetry of renal perfusion disclosed by this technique. Thus, ancillary renal imaging with thallium-201 can be used to identify hypertensive patients who should be considered for renal angiographic evaluation.

Diagnostic accuracy and pitfalls of [iodine-131]6-beta-iodomethyl-19-norcholesterol (NP-59) imaging.

NP-59 concentrates in steroid hormone synthesizing tissues, enabling scintigraphic localization and characterization of endocrine dysfunction in the adrenal cortex and ovary. Studying 108 consecutive cases from 1982 to 1985 and using clinical, biochemical, radiographic, and pathologic data, we performed a rigorous assessment of the accuracy and pitfalls of NP-59 scintigraphy. The evaluation was divided into categories of abnormal hormone secretion: Cushing's syndrome, primary aldosteronism, and hyperandrogenism. Additional categories included euadrenal tumors (without detectable hormone dysfunction) and sites of residual adrenal cortical tissue. The accuracy of NP-59 scintigraphy ranged from 71% in primary aldosteronism and 75% in euadrenal tumors, to 100% for Cushing's syndrome and hyperandrogenism. However, more than in most nuclear medicine studies, NP-59 imaging requires well-defined indications to be met for it to be efficacious, including the fulfillment of clear clinical, biochemical, and radiographic criteria. The high reproducibility of NP-59 scintigraphic interpretation was demonstrated when 40 random cases underwent interinstitutional exchange and through interobserver evaluation at the University of Michigan. Responses of 85/126 medical centers to questionnaires revealed the high level of NP-59 safety.

Renal uptake of Tl-201 in hypertensive patients undergoing myocardial perfusion imaging.

The detection of renovascular disease (RVD) has particular relevance in hypertensive patients (HP) who have symptoms of target organ damage. To evaluate the possibility of RVD in HP undergoing myocardial perfusion scintigraphy for chest pain symptoms, posterior renal images were obtained at 1-3 hours after Tl-201 injection. Analog and computer images were obtained for 5 minutes in 45 HP; 12 patients with no history of hypertension or renal disease served as normal controls. For qualitative analysis, images were coded and read by three observers as to symmetry of renal uptake. Differential renal uptake of Tl-201 (DRU) was quantitated on computer images. In normal controls, uptake was agreed on as symmetric. In HP, 6 patients had marked asymmetry of DRU and 4 had possibly significant asymmetry; 2 had decreased uptake in both kidneys suggesting bilateral RVD or nephrosclerosis. Objective correlation with DRU was obtained in 10 HP who had contrast angiography, confirming 4 cases of unilateral RVD and 2 of bilateral RVD. Thirteen patients also had renography with Tc-99m DTPA; differential renal function by this modality correlated well with DRU of Tl-201 (r = 0.98). Thus, DRU of Tl-201 can be used as a supplement to myocardial scintigraphy to identify HP who require further evaluation and treatment of RVD.

Cerebral perfusion imaging with technetium-99m HM-PAO in brain death and severe central nervous system injury.

We performed 38 cerebral perfusion studies in 33 patients with brain death or with severe central nervous system injury using technetium-99m hexamethyl-propyleneamine oxime [( 99mTc]HM-PAO). Uptake by the cerebrum and/or cerebellium was present in all patients who were not clinically brain dead (ten studies) although the study was often abnormal. In those patients who were brain dead, 16/17 studies demonstrated no uptake in either the cerebrum or cerebellum. In patients suspected of brain death, but who had conditions interfering with the diagnosis the test demonstrated no uptake in 9/11 studies, confirming brain death. A radionuclide angiogram (RNA) of the head was also performed in 33/38 studies and showed complete agreement with the [99mTc]HM-PAO uptake, except in one case. We conclude that cerebral perfusion imaging with [99mTc]HM-PAO is a simple, noninvasive and reliable test to confirm brain death. By comparison with conventional technetium agents, [99mTc]HM-PAO is not dependent on the quality of the bolus injection, is easier to interpret and allows evaluation of posterior fossa blood flow.

Impact on surgery of preoperative localization of parathyroid lesions with dual radionuclide subtraction scanning.

In an effort to localize parathyroid lesions preoperatively, scanning with radioactive thallium and technetium was performed in 20 patients considered clinically to have hyperparathyroidism. In the 11 found at surgery to have single parathyroid adenomas, scanning correctly localized the lesion in 10; in the other patient the lesion was in the unscanned mediastinum. Preoperative scanning was not as rewarding in the seven patients with parathyroid hyperplasia. A thyroid lesion was the source of an abnormality seen on the parathyroid scan in one patient, while neck scanning and surgical exploration were negative in another. Comparison of the patients who had parathyroid adenomas localized in the neck with a control group of similar patients who did not undergo preoperative scanning showed that the average surgical time was reduced by 50% with preoperative localization and there was a decrease in the number of nonparathyroid tissue biopsies.

Ventilation imaging with Kr-81m. A comparison with Xe-133.

Sixty-five patients with suspected pulmonary embolism were studied prospectively with both Kr-81m and Xe-133 ventilation imaging and Tc-99m MAA perfusion imaging. The krypton images, perfusion scintigrams and chest radiographs were read independently of the xenon images, perfusion scintigrams and chest radiographs by three observers. The studies of 53 patients were interpreted as normal or as indicative of a low or intermediate probability for pulmonary embolism with both gases. One study indicated intermediate probability with Xe-133 due to diffuse, severe xenon retention but low probability with Kr-81m because of close ventilation-perfusion correspondence. The studies of 9 patients indicated a high probability of embolism with both gases, while those of two additional patients (one with emboli at angiography) indicated a high probability only with Kr-81m. While essential agreement between Xe-133 and Kr-81m ventilation imaging was found in most patients, the significant difference in interpretation in 2 of 11 patients with probable pulmonary embolism suggests that a controlled, prospective trial with pulmonary angiography is warranted before Kr-81m is employed for routine clinical use.

Ventilation-perfusion studies in suspected pulmonary embolism.

The results of ventilation-perfusion (V-Q) imaging and pulmonary angiography were retrospectively analyzed in 146 patients with suspected pulmonary embolism (PE) to define the frequency of PE associated with various scintigraphic patterns. When the radionuclide images demonstrated at least two moderate-sized or one large area of V-Q mismatch, the probability of PE was 92%. However, only one of three patients with a single moderate-sized V-Q mismatch had PE, while small V-Q mismatches were not associated with PE in any of 19 patients. Matched V-Q abnormalities in lung regions that were radiographically normal were infrequently due to PE (4.8%). When a perfusion defect was substantially smaller than a corresponding radiographic abnormality, the frequency of PE was low (7.7%). Conversely, when a perfusion defect was substantially larger than the corresponding radiographic abnormality, there was a high probability of PE (87%). Matched perfusion and radiographic abnormalities indicated an intermediate probability of PE (27%). Patients with suspected pulmonary embolism may be classified into groups with low, intermediate, or high probability of pulmonary embolism on the basis of size and number of perfusion defects and a careful comparison of perfusion defects with ventilatory and radiographic findings.