Evaluation of mammary lymphoscintigraphy by a single intratumoral injection for sentinel node identification.

The aim of this study was to evaluate the findings of mammary lymphoscintigraphy by a single intratumoral injection in 150 patients with breast carcinoma: 100 patients (group A) investigated in the validation phase of the study and 50 (group B) studied after the tracer dose was optimized. METHODS: Immediately after injection of 99mTc-nanocolloid using a 25-gauge needle and a 0.2-mL volume, simultaneous anterior and lateral images were acquired with a dual-head gamma camera during 20 min followed by sequential static anterior and prone lateral breast images after 30 min and after 2 and 4 h. 57Co-assisted skin marking defined the sentinel node location for subsequent gamma probe, blue dye-guided sentinel node biopsy. RESULTS: In group A (mean dose, 61.6 MBq; range, 42-88 MBq) scintigraphy revealed lymph nodes in 83 patients (83%), with an increase in the rate of visualization from 72% for the first 40 patients to 90% for the last 60; patient age (P = 0.01) and administered tracer dose (P = 0.04) were found to be significant factors for visualization, with optimal results obtained from doses higher than 65 MBq. Lymph nodes were visible in 34 patients (41%) during the first 30 min after injection, whereas in 49 patients appearance occurred at 2-4 h. A total of 97 lymphatic basins were visualized (80 axillary, 3 clavicular, 14 internal mammary). In group B (mean dose, 90.8 MBq; range, 68-124 MBq), the visualization rate was 94%, with early lymph node appearance in 27 patients (57%) and a total of 53 basins (45 axillary, 8 internal mammary). In combination with intraoperative blue dye mapping and y probing, the identification rate increased to 90% in group A and 98% in group B. Prone lateral images contributed to identification of intramammary lymph nodes in a total of 14 patients and axillary nodes close to the injection site in 8 other patients. CONCLUSION: Mammary lymphoscintigraphy by single intratumoral injection is a valid method for lymphatic mapping and identification of both axillary and nonaxillary sentinel nodes. Lymph node visualization appears to be improved with higher tracer doses. The compactness of the injection site enables high-quality additional lateral images that can depict intramammary or axillary lymph nodes adjacent to the injection site.     

Lymphoscintigraphy with 99mTc-DTPA-HSA: detection of metastases to iliopelvic lymph nodes

The purpose of this study was to evaluate 99mTc-DTPA-HSA as an iliopelvic lymphoscintigraphic agent in 5 normal volunteers and 10 patients with metastases of malignant tumors (cancer, 9; and malignant lymphoma, 1) to the iliopelvic lymph nodes. The subjects underwent intradermal injection of 185 MBq of 99mTc-DTPA-HSA into digital web spaces of the feet. Massage was applied at the injection sites for 30 sec; the subjects then walked around for 2 min. Whole-body scintigrams were obtained 5 min after injection. The whole-body scanning speed was 20 cm/min. The tracer transport was prompt. Within 15 min after injection, the tracer reached the termination of the thoracic duct in all normal volunteers. Normal whole-body images of excellent quality delineated the lymph nodes and channels almost without background radioactivity. The images of 9 patients with metastases of cancer showed clearly the following abnormal patterns: a) obstruction of lymphatic system (5/9, 55.6%); b) absence of visualization of the thoracic duct (44.4%); c) decreased uptake in lymph nodes (88.9%); d) visualization of collateral circulation (44.4%); e) tracer extravasation into more proximal soft tissue (22.2%). The image in the patient with malignant lymphoma showed increased uptake in the enlarged lymph nodes in addition to the all abnormal findings mentioned above. We concluded that 99mTc-DTPA-HSA is an excellent radiopharmaceutical for iliopelvic lymphoscintigraphy.     

Evaluation of 99mTc-dextran as a lymphoscintigraphic agent in rabbits

Dextran (clinical grade, average mol. wt. 82,200) was labelled with 99mTc and the labelling efficiency was checked by paper and thin-layer chromatography and electrophoresis. The amount of free 99mTcO-4 was always less than 1%. The radiopharmaceutical was injected ID into the web space in hind legs of ten rabbits (200-600 microCi/0.05 ml). Scintigrams were taken at 10-min intervals up to 3 h in three rabbits. The injection site and the hind legs were massaged after injection in the other seven rabbits and scintigrams were taken at 10-min intervals up to 2 h. Blood samples were obtained at 5, 15, 30, 90 and 120 min in both groups. In addition a 180-min sample was also taken in the first group. At the end of the study the rabbits were killed and the popliteal lymph nodes and the organs were removed to be weighed and counted. Our results indicated a high concentration of radioactivity in the popliteal lymph nodes and massage at the injection site increased the average uptake of the popliteal lymph node from 1.12% +/- 0.77% to 4.28% +/- 1.57% at 3 and 2 h, respectively (P less than 0.001). In scintigrams the lymph channels and the nodes were very well visualised. The blood radioactivity levels were too low to present a background problem. With massage 30% of the injected dose was removed from the injection site in 2 h. We have shown that 99mTc-dextran is a good radiopharmaceutical for the visualisation of the lymph system and deserves further experimental and clinical studies.     

Comparison as a lymphoscintigraphic agent between 99Tcm dextran and 99Tcm antimony sulphide colloid

To determine its suitability as a lymph node imaging agent, 99Tcm dextran (99TcmDx) was compared with 99Tcm antimony sulphide colloid (99TcmSb2S3) in rabbits and dogs. In two groups of five rabbits each, absorption from the interstitial injection site, popliteal lymph node sequestration and total body uptake and distribution of both agents were determined. In three dogs, both agents were studied simultaneously, 99TcmDx and 99TcmSb2S3 being injected into the left and right hind feet respectively; therefore, only popliteal lymph node sequestration and image qualities were evaluated. Uptake curves in the rabbits indicated that total body uptake of 99TcmDx is faster and greater than that of 99TcmSb2S3. In spite of rapid lymph node uptake rates, total popliteal lymph node sequestration of 99TcmDx is significantly lower than that observed for 99TcmSb2S3. While lymph node uptake of 99TcmDx in dogs is higher than in rabbits, disparity between the two agents persists and is demonstrable in the image in both species. Reduced lymph node sequestration of 99TcmDx may result from its non-colloidal nature as well as its instability, both of which render this agent unsuitable for imaging pathological features of lymph nodes although its rapid absorption and distribution may be ideal characteristics for the study of lymphatic kinetics.     

Pelvic lymph node visualization with MR imaging using local administration of ultra-small superparamagnetic iron oxide contrast

PURPOSE: To determine if interstitial injection of iron oxide particles improves visualization of pelvic lymph nodes at magnetic resonance imaging (MRI) and to determine the effect of injection site on location of visualized nodes. MATERIALS AND METHODS: In nine healthy volunteers, ferumoxtran-10 iron oxide (0.28 mg iron per kg) was injected into the anterior thigh (three subjects) or perianal (three subjects) or periprostatic tissues (three subjects). MRI at 1.5 T was performed before injection and one, three, and seven days after injection. RESULTS: The mean of 30 nodes seen post-injection was greater than the mean of 5.8 seen pre-injection (P < 0.001). After thigh injection, a mean of three internal vs. 36 external nodes were seen. Compared with thigh injection, there was a higher fraction of internal nodes with perianal (mean of nine internal vs. 14 external, P < 0.001) and periprostatic injection (mean of 11 internal vs. five external, P < 0.001). More nodes were seen with gradient-echo sequences than with other sequences (P < 0.001). CONCLUSION: Interstitial injection of iron oxide particles increases visualization of pelvic lymph nodes. Perianal and periprostatic injection increases the number of internal pelvic lymph nodes seen compared with thigh injection.     

Measurement of lymphatic function with technetium-99m-labelled polyclonal immunoglobulin.

A reliable method for measuring lymph flow in physiological units would be valuable, especially in conditions in which it is uncertain whether lymph flow is increased or decreased. The requirements of a radiopharmaceutical for such measurement include stable radionuclide labelling and rapid access to lymphatic vessels following tissue injection but no access to blood vessels. A soluble macromolecule is likely to come closest to meeting these requirements. Technetium-99m-labelled human polyclonal immunoglobulin (HIG) was therefore investigated firstly in comparison with 99mTc-labelled human serum albumin (HSA) in patients undergoing routine lymphoscintigraphy and secondly with respect to injection site in a group of volunteers with post-mastectomy oedema (PMO). Subcutaneous injection of 99mTc-HIG into the web space of a distal extremity gave images in which lymphatic vessels were more clearly defined compared with images obtained after injection of 99mTc-HSA. Lymph nodes were also more clearly defined, suggesting specific retention of HIG, possibly through Fc-mediated binding. Peripheral blood sampling showed a delayed arrival in blood of radioactivity after 99mTc-HIG compared with 99mTc-HSA, although ultimately, the blood recovery of 99mTc-HIG was significantly higher (P < 0.05) than that of 99mTc-HSA. Clearance rates of radioactivity from the injection site were not significantly different, however, between the two agents. In patients with PMO, web space injection of 99mTc-HIG gave excellent images of normal lymphatic vessels, of lymph nodes and of abnormal lymph drainage such as dermal backflow in swollen arms. In contrast, neither lymphatic vessels nor lymph nodes were visualised after injection into the skin of the dorsum of the distal forearm. Although there was no difference in clearance rates from the injection sites between normal and swollen arms with either agent in PMO, clearance was significantly faster following injection into the web space (0.11% per minute for normal and swollen arms combined) than into the forearm (0.053% per minute; P < 0.05). These results suggest that (a) 99mTc-HIG is a potentially useful agent for measuring lymph flow and lymph node function; but (b) injection into the dorsum of the forearm is not a useful method of administration for these measurements; and (c) clearance rates from the injection site do not support the notion that PMO is the result of decreased lymph flow. Further studies are warranted to evaluate 99mTc-HIG as an agent for assessment of lymphatic function, especially with respect to measurement of lymph flow and possibly also for the evaluation of lymph node Fc-mediated immunocompetence.     

99锝m N-2-巯基吡啶-N-氧化物与99锝m-甲氧基异丁基异腈对犬急性心肌梗死模型的对照研究

目的 在正常和心肌梗死犬模型上,研究99TcmN-2-巯基吡啶-N-氧化物(99TcmN-MPO)的药物代谢动力学特征、生物学分布特征和对急性心肌梗死的诊断能力,并与传统示踪剂99锝m-甲氧基异丁基异腈(99Tcm-MIBI)进行对比研究.方法 正常杂种犬12只.静脉注射99TcmN-MPO,于不同时间点(30 s及1、2、3、4、5、10、20、30、40、60和90 min)静脉分别采血1 ml,经γ探测器测量其放射活性;注药后10、20、30、60、90及120 min行全身SPECT显像,并于不同器官上各取同样大小的ROI,测量其放射性计数进行定量研究.每只犬均注射相同剂量的99TcmMIBI,进行相同的实验作为对照.介入学方法构建犬急性心肌梗死模型,24 h后,静脉注入99TcmN-MPO(5只)和99Tcm-MIBI(5只),并于注药后30、60min进行心肌SPECT显像.结果 在静脉注射90 min内,99TcmN-MPO和99Tcm-MIBI均表现为快速的血液清除.两种示踪剂的初始注射剂量均为370 MBq.注射后1 min,每毫克血浆的放射活性小于初始注射剂量的50%[99TcmN-MPO为(35.77±6.31)%ID/mg;99Tcm-MIBI为(34.46±6.83)%ID/mg],30 min时＜5%[99TcmN-MPO:(3.11±1.44)%ID/mg;99Tcm-MIBI:(2.93±0.39)%ID/mg].99TcmN-MPO在心脏的浓聚明显,且存留时间很长,由于其在肝脏清除的速度较快,因此可获得良好的心/肝摄取比值,注射后10 min为0.54±0.06,30 min为1.02±0.06,60 min上升到1.38±0.06.相比之下,99Tcm-MIBI的心/肝摄取比值上升较为缓慢(注射后10 min为0.46±0.03,30 min为0.63±0.03,60 min为0.62±0.12).犬心肌梗死后SPECT心肌断层扫描显示,在注射99TcmN-MPO 30 min后,心脏与肝脏分界清楚,可清楚显示心肌缺血、梗死灌注缺损区域、范围和程度;而99Tcm-MIBI注射后60 min,心脏和肝脏的分界依然不清,尤其是肝脏的高放射性对心脏下壁和左心室壁的影响很大,对心脏左心室壁的心肌梗死灌注缺损区域的显示不佳.结论 99TcmN-MPO具有心肌摄取量较高,肝脏代谢快的特点,是一种具有广阔临床应用前景的SPECT心肌灌注成像显像剂.

Abstract：

Objective The purpose of the present study is to compare the pharmacokinetic and biodistribution properties of 99Tcm N-mercaptopyridine-N-oxide (99 Tcm N-MPO) with 99 Tcm-sestamibi (99 Tcm-MIBI) in normal dogs, and to investigate the potential of 99TcmN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction. Methods Twelve healthy mongrel dogs were injected intravenously with 99TcmN-MPO (n = 6) or 99Tcm-MIBI (n = 6). Tracer kinetics in body fluids were determined by collecting blood of 1 ml via a femoral vein catheter at 30 s, 1,2,3,4,5, 10, 20, 30, 40, 60and 90 min post-injection (p. i.). The collected blood samples were weighed and counted for radioactivity in a γ-counter. Anterior and posterior planar γ-camera images were collected at 10, 20, 30, 60, 90, and 120 min after injection, with organ uptake quantified by region-of-interest (ROIs) analysis. For comparison, 99Tcm-MIBI was also evaluated in the same twelve dogs. Canine infarct models were set up by micro-invasive interventional embolization. SPECT images in the canine infarct model were collected 24 hours after myocardial infarction at 30 min and 60 min after the administration of 99Tcm N-MPO (n = 5) or 99Tcm-MIBI (n = 5). Results Both of 99Tcm N-MPO and 99Tcm-M1BI had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min [99TcmN-MPO: (35. 77 ± 6. 31)% ID/mg ,99Tcm-MIBI (34. 46 ± 6. 83) % ID/mg] and less than 5% at 30 min p. i. [99Tcm N-MPO(3. 11 ± 1.44) % ID/mg,99Tcm-MIBI (2.93 ±0. 39)% ID/mg] . After injection, 99TcmN-MPO showed significant accumulation in the myocardium and prolonged retention. This rapid liver clearance of 99TcmN-MPO led to favorable heart-to-liver ratios, reaching values of 0. 54 ±0. 06 at 10 min, 1.02 ±0. 06 at 30 min, and 1.38 ±0. 06 at 60 min p. i.In contrast, the heart/liver ratio of 99Tcm-MIBI remained low at all time points (0. 46 ± 0. 03 at 10 min,0. 63 ±0. 03 at 30 min, and 0. 62 ± 0. 12 at 60 min p. i.). SPECT imaging studies in canines with acute myocardial infarction indicated that good visualization of the left ventricular wall and perfusion defects could be achieved at 30 min after administration of 99TcmN-MPO, but not 99Tcm-MIBI. Conclusion The combination of high heart uptake and rapid liver clearance makes 99TcmN-MPO a promising new radiotracer for myocardial perfusion imaging.     

Radiolabelled granulocytes in inflammatory bowel disease: diagnostic possibilities and clinical indications

Radiolabelled granulocytes in chronic inflammatory bowel diseases (CIBD) are able to diagnose the disease extent and assess the disease activity. It may be performed with 111In oxine- and 99Tcm hexamethylpropyleneamineoxime (HMPAO)-labelled cells. The granulocyte scan localizes inflamed bowel segments with an accuracy comparable with radiology and endoscopy including biopsy of the bowel (r = 0.95; P less than 0.001). The specificity of the scan for diseased segments is near 100%, the sensitivity 92%. A three-phase white blood cell scan (imaging: 0.5, 4, 20 h post injection) allows differentiation of diseased bowel segments from abscesses and fistulas. False positive results are possible in necrotic carcinomas. The 99Tcm HMPAO scan shows rapid renal and delayed biliary and intestinal excretion of tracer. In this way diagnostic problems arise in the small pelvis. Because of the intestinal and biliary excretion, early images should be obtained (0.5-2 h post injection). Later scans with 99Tcm HMPAO are of minor importance. The disease activity can very specifically be assessed by the determination of the percentage faecal 111In excretion (96 h faecal collection). Active and non-active diseases can be clearly differentiated. We found no correlation with the subjectively influenced Crohn's disease activity index (CDAI) (r = 0.25; P greater than 0.05), but good correlations with the Dutch Index (van Hees: r = 0.67), ESR (r = 0.69), serum albumin (r = -0.54) and orosomucoid (r = 0.65). The percentage faecal excretion correlates well with the histologically estimated leucocytic bowel infiltration. Because of the intestinal 99Tcm HMPAO excretion the determination of faecal excretion is pointless in 99Tcm studies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical experience with intra lymphatic administration of111In-labelled monoclonal antibody PAY 276 for the detection of pelvic nodal metastases in prostatic carcinoma

The ability of¹¹¹In-PAY 276 (anti prostatic acid phosphatase antibody) in detecting pelvic lymph node metastasis following bipedal intra lymphatic administration was studied in five patients with carcinoma of the prostate. The labeled antibody was injected directly into the lymphatics of each foot. Planar and tomographic images radioactivity content of lymph nodes resected during staging pelvic lymphadenectomy were compared to the histologic and immunoperoxidase findings. Radioactivity in pelvic lymph nodes was prominently seen within 20 min of injection and was present 16 days later. Persistent accumulation of tracer in the lymphatics of the lower extremities was also observed in all patients 16 days post injection. Radioactivity counts in tumor-free lymph nodes were higher than in tumored lymph nodes resected. Our results demonstrate that intra lymphatic administration of¹¹¹In-labeled PAY 276 monoclonal antibody has major technical limitations, and that further research directed at the causes of tracer accumulation in the lymphatics and tumor-free lymph nodes is required.     

Lymphatic mapping with 99mTc-Evans Blue dye in sheep

Objective   ^99mTc-Evans Blue (EB) is an agent that contains both radioactive and color signals in a single dose. Earlier studies in animal models have suggested that this agent when compared with the dual-injection technique of radiocolloid/blue dye can successfully discriminate the sentinel lymph node. The aim of this study was to investigate the potential of ^99mTc-EB as an agent to map the lymphatic system in an ovine model. Methods  Doses of ^99mTc-EB (23 MBq) containing EB dye (4 mg) were administered intradermally to the limbs of four anesthetized sheep, and they were then imaged over 20–30 min using a gamma camera. The study protocol was repeated using ^99mTc-antimony trisulfide colloid (ATC) and Patent Blue V dye. The lymph nodes (popliteal, inguinal, and iliac for hind limbs or prescapular for fore limbs) were identified with a gamma probe during the operative exposure, then dissected and counted in a large volume counter. Results  Simple and complex (dual) drainage patterns were visible on the scans, and the sentinel node was more radioactive than higher tier nodes in a chain, for both radiotracers. For ^99mTc-EB, maximum radioactive uptake was achieved at 3–6 min for popliteal lymph nodes, 12–14 min for iliac nodes, and 13–14 min for prescapular nodes. ^99mTc-ATC resulted in maximum radioactive uptake at 4–6 min for popliteal lymph nodes, 13 min for an inguinal node, 13–20 min for iliac nodes, and 18 min for a prescapular node. Following ^99mTc-EB injection, 15/15 lymph nodes harvested were all radioactive and blue. For ^99mTc-radiocolloid/Patent Blue V injection, 8/14 nodes were radioactive and blue, and 6/14 nodes were radioactive only. Conclusions  The soluble radiotracer ^99mTc-EB appeared to be a useful lymphoscintigraphic agent in sheep, in which radioactive counts from superficial lymphatic channels and lymph nodes were sufficient for planar imaging. In comparison with ^99mTc-antimony trisulfide colloid, both tracers discriminated the sentinel lymph node up to 50 min after administration; however, ^99mTc-EB had the advantage of providing radioactive (gamma probe) and color signals simultaneously during the operative exposure.     

Clinical experience with intra lymphatic administration of 111In-labelled monoclonal antibody PAY 276 for the detection of pelvic nodal metastases in prostatic carcinoma

The ability of 111In-PAY 276 (anti prostatic acid phosphatase antibody) in detecting pelvic lymph node metastasis following bipedal intra lymphatic administration was studied in five patients with carcinoma of the prostate. The labeled antibody was injected directly into the lymphatics of each foot. Planar and tomographic images radioactivity content of lymph nodes resected during staging pelvic lymphadenectomy were compared to the histologic and immunoperoxidase findings. Radioactivity in pelvic lymph nodes was prominently seen within 20 min of injection and was present 16 days later. Persistent accumulation of tracer in the lymphatics of the lower extremities was also observed in all patients 16 days post injection. Radioactivity counts in tumor-free lymph nodes were higher than in tumored lymph nodes resected. Our results demonstrate that intra lymphatic administration of 111In-labeled PAY 276 monoclonal antibody has major technical limitations, and that further research directed at the causes of tracer accumulation in the lymphatics and tumor-free lymph nodes is required.     

Phytate technetium-99m versus dextran 500 technetium-99m in the sentinel lymph node biopsy

PURPOSE: To study which of the two most used radiopharmaceutical drugs for the sentinel lymph node (SLN) biopsy procedure (dextran 500 99mTc and phytate 99mTc) best defines the SLN and migrates less to other lymph nodes. MATERIAL AND METHODS: Thirty-two rats, separated into two groups, underwent lymphoscintigraphy examination with either dextran or phytate followed by sentinel (popliteal), lumbar, and inguinal lymph node biopsy. Radiation was detected with a gamma probe. RESULTS: The statistical study indicated count rates significantly higher in the SLN than in the other basins for both the dextran (P<0.01) and phytate groups (P<0.001). There was no statistically significant difference concerning SLN absorption in either group (P=0.2981). In the dextran group, migration occurred to 1.5 lymphatic basins with counting higher than 10% of that found in the SLN versus 0.8 in the phytate group (P=0.0023). Migration was thus higher in the dextran group (P=0.0207). CONCLUSION: There was no statistically significant difference between dextran and phytate in the SLN identification, but the phytate migrated to fewer lymphatic basins beyond the SLN and with less intensity.     

Detection of inflammatory lymph nodes in rabbits by 99mTc-HIG lymphoscintigraphy

Tc-Human immunoglobulin G ( Tc-HIG) is a well-known radiopharmaceutical for the evaluation of inflammatory lesions. Recently, it has been demonstrated as a new agent for the visualization of the lymphatic system by our group. Our aim was to investigate the feasibility of detection of inflammatory lymph nodes by Tc-HIG lymphoscintigraphy. Ten adult New Zealand rabbits were used as group A. In a baseline study, 37 MBq Tc-HIG (0.1 ml) was injected into both hind legs of the rabbits, and sequential posterior gamma imaging with the rabbits lying prone was performed at 5, 15, 30, 60, 90 and 120 min using a single-headed gamma camera (Toshiba GCA G01 E). One week later, microorganisms ( ) were injected in a volume of 0.1 ml intradermally into the web space between the second and third toes in the bilateral hind legs of each rabbit in order to obtain inflammation in the popliteal lymph nodes. After 4 days, 37 MBq Tc-HIG (0.1 ml) was injected into the hind legs of the rabbits bilaterally, and sequential posterior gamma imaging was performed as described above (second study). Another group of 10 adult New Zealand rabbits (group B) was injected with the same microorganisms in the right hind legs only. After 4 days, scintigraphic imaging was carried out in the same way as described above (third study). Regions of interest were drawn over the injection sites and popliteal lymph nodes on each image for semiquantitative analysis. Count rates for each were calculated and a decay correction was applied. Time-activity curves were generated to show the percentage retention of radioactivity in each region. After the scintigraphic study, some of the group B rabbits were killed by intravenous injection of pentobarbitone (100-150 mg.kg, and both left and right lymph nodes were removed for microscopic examination. On the scintigrams, lymphatic channels and popliteal lymph nodes were visualized within 15 min. In the second study, bilateral popliteal lymph nodes were visualized more clearly than in the baseline study. The right popliteal lymph nodes of the rabbits were more clearly visualized in the third study. Semiquantitative analysis showed a higher percentage uptake of radioactivity in the right compared to the left popliteal lymph nodes in group B rabbits. Microscopic examination of the tissue sections demonstrated inflammation in the right lymph nodes of group B rabbits. In this preliminary study, it was found that Tc-HIG is a new promising agent for the demonstration and evaluation of inflammatory lymph nodes.     

Improved sentinel node visualization in breast cancer by optimizing the colloid particle concentration and tracer dosage

Faint lymph uptake may hamper sentinel node (SN) identification by scintigraphy and subsequent gamma probe localization. The aim of the present study was to evaluate an adjustment in the colloid particle concentration and tracer dosage to optimize mammary lymphoscintigraphy. Scintigraphy was performed in 151 patients with a palpable breast carcinoma and clinically negative axilla: for the first 75 patients (group A) a standard labelling of 0.5 mg nanocolloid with 99Tcm was performed, for the subsequent 76 patients (group B) the labelling dilution volume was reduced from 4 to 2 ml. For both groups the volume of injection was 0.2 ml. Lymph node uptake was evaluated by a 4-step visual score (from 0 = absent to 3+ = very intense), and by count quantification of at 4 h in the first draining SN. The SN visualization rate increased from 93% (70/75) in group A (mean dosage 93.4 MBq, range 57-130 MBq) to 99% (75/76) in group B (mean dosage 106.5 MBq, range 74-139 MBq). The percentage of patients with uptake 3+ was significantly higher (P = 0.001) in group B (51% vs 35% in group A). SN counts were significantly higher for group B (P<0.001). The percentage of patients with less than 2000 counts/node diminished from 45% in group A to 9% in group B (P = 0.001). In group B (P = 0.033) more lymph channels (53% vs 35% in group A) were visualized and for a longer time (26% vs 4% at 4 h). Axillary drainage was seen in 96% in group A and 98% in group B whereas non-axillary drainage was observed in 19% and 25%, respectively. Intraoperative SN identification rate was 97% in group A and 100% in group B. SN metastases were found in 41% of group A and 47% of group B. It is concluded that enhancement of colloid particle concentration and adjustment of tracer dosage led to improved SN identification by substantial increase in lymph node uptake and lymph vessel depiction. A significant reduction of cases with faint SN uptake enables better surgical efficacy.     

Measurement of lymphatic function with technetium-99m-labelled polyclonal immunoglobulin

A reliable method for measuring lymph flow in physiological units would be valuable, especially in conditions in which it is uncertain whether lymph flow is increased or decreased. The requirements of a radiopharmaceutical for such measurement include stable radionuclide labelling and rapid access to lymphatic vessels following tissue injection but no access to blood vessels. A soluble macromolecule is likely to come closest to meeting these requirements. Technetium-99m- labelled human polyclonal immunoglobulin (HIG) was therefore investigated firstly in comparison with ^99mTc-labelled human serum albumin (HSA) in patients undergoing routine lymphoscintigraphy and secondly with respect to injection site in a group of volunteers with post-mastectomy oedema (PMO). Subcutaneous injection of ^99mTc-HIG into the web space of a distal extremity gave images in which lymphatic vessels were more clearly defined compared with images obtained after injection of ^99mTc-HSA. Lymph nodes were also more clearly defined, suggesting specific retention of HIG, possibly through Fc-mediated binding. Peripheral blood sampling showed a delayed arrival in blood of radioactivity after ^99mTc-HIG compared with ^99mTc-HSA, although ultimately, the blood recovery of ^99mTc-HIG was significantly higher (P <0.05) than that of ^99mTc-HSA. Clearance rates of radioactivity from the injection site were not sinificantly different, however, between the two agents. In patients with PMO, web space injection of ^99mTc-HIG gave excellent images of normal lymphatic vessels, of lymph nodes and of abnormal lymph drainage such as dermal backflow in swollen arms. In contrast, neither lymphatic vessels nor lymph nodes were visualised after injection into the skin of the dorsum of the distal forearm. Although there was no difference in clearance rates from the injection sites between normal and swollen arms with either agent in PMO, clearance was significantly faster following injection into the web space (0.11% per minute for normal and swollen arms combined) than into the forearm (0.053% per minute; P<0.05). These results suggest that (a) ^99mTc-HIG is a potentially useful agent for measuring lymph flow and lymph node function; but (b) injection into the dorsum of the forearm is not a useful method of administration for these measurements; and (c) clearance rates from the injection site do not support the notion that PMO is the result of decreased lymph flow. Further studies are warranted to evaluate ^99mTc-HIG as an agent for assessment of lymphatic function, especially with respect to measurement of lymph flow and possibly also for the evaluation of lymph node Fc-mediated immunocompetence. Received 28 July and in revised form 26 October 1998     

Influence of fast lymphatic drainage on metastatic spread in cutaneous malignant melanoma: a prospective feasibility study

The concept of sentinel lymph node biopsy in cutaneous malignant melanoma is widely established. Preoperative cutaneous lymphoscintigraphic mapping is a reliable method for identifying the nodal basins at risk of metastases in melanomas. In this prospective study we investigated the correlation between the scintigraphic appearance time and the metastatic involvement of sentinel lymph nodes. In 276 malignant melanoma patients (137 women, 139 men; age 16-93 years), dynamic and static lymphoscintigraphy was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour or biopsy scar. Analysis of dynamic scans primarily focussed on the appearance time of sentinel lymph nodes. Sentinel lymph node visualisation 20 min as slow drainage. Fast lymphatic drainage was found in 236 patients, of whom 34 (14.4%) had sentinel lymph node metastases. Twenty-two patients showed hybrid (fast and slow) lymphatic drainage, and eight (36.4%) of them had sentinel lymph node metastases. Seven of the latter demonstrated fast lymphatic drainage, while one showed one positive sentinel lymph node with fast and another with slow drainage. The melanomas of 18 patients demonstrated exclusively slow lymphatic drainage, in all cases without sentinel lymph node metastases. This prospective study indicates that the scintigraphic appearance time of sentinel lymph nodes seems to be a clinically relevant factor for prediction of metastatic spread of cutaneous malignant melanoma. Larger numbers of patients need to be examined to truly assess the benefit of the scintigraphic appearance time compared with other predictors of sentinel lymph node tumour positivity.     

Finding an optimal method for imaging lymphatic vessels of the upper limb

Lymphoscintigraphy involves interstitial injection of radiolabelled particulate materials or radioproteins. Although several variations in the technique have been described, their place in clinical practice remains controversial. Traditional diagnostic criteria are based primarily on lymph node appearances but in situations such as breast cancer, where lymph nodes may have been excised, these criteria are of limited use. In these circumstances, lymphatic vessel morphology takes on greater importance as a clinical endpoint, so a method that gives good definition of lymphatic vessels would be useful. In patients with breast cancer, for example, such a method, used before and after lymph node resection, may assist in predicting the development of breast cancer-related lymphoedema. The aim of this study was to optimise a method for the visualisation of lymphatic vessels. Subcutaneous (sc) and intradermal (id) injection sites were compared, and technetium-99m nanocolloid, a particulate material, was compared with ^99mTc-human immunoglobulin (HIG), which is a soluble macromolecule. Twelve normal volunteers were each studied on two occasions. In three subjects, id ^99mTc-HIG was compared with sc ^99mTc-HIG, in three id ^99mTc-nanocolloid was compared with sc ^99mTc-nanocolloid, in three id ^99mTc-HIG was compared with id ^99mTc-nanocolloid and in three sc ^99mTc-HIG was compared with sc ^99mTc-nanocolloid. Endpoints were quality of lymphatic vessel definition, the time after injection at which vessels were most clearly visualised, the rate constant of depot disappearance (k) and the systemic blood accumulation rate as measured by gamma camera imaging over the liver or cardiac blood pool. Excellent definition of lymphatic vessels was obtained following id injection of either radiopharmaceutical, an injection route that was clearly superior to sc. Differences between radiopharmaceuticals were less clear, although after id injection, ^99mTc-HIG gave images that were marginally but significantly better than those given by ^99mTc-nanocolloid. Image quality correlated inversely with time after injection at which the best image was obtained, consistent with the notion that good vessel definition was dependent on a narrow bolus width. k was approximately three times higher after id injection than after sc injection but it was not significantly different between radiopharmaceuticals for either injection route. Intradermal ^99mTc-HIG gave a cardiac blood pool signal that, over the first 60 min, increased about five times faster than that with sc ^99mTc-HIG, but no clear difference was observed in the rate of increase in hepatic activity between id ^99mTc-nanocolloid and sc ^99mTc-nanocolloid. We conclude that id injection provides rapid access of radiotracers to lymphatic vessels, which is ideal for imaging lymphatic vessel morphology. ^99mTc-HIG is marginally superior to nanocolloid for this purpose and, in drainage basins from which lymph nodes have been excised, is not handicapped by a potentially inferior ability, compared with radiocolloid, to image lymph nodes.     

新型心肌显像剂[99Tcm(N)(PNP5)(DBODC)]+猪心肌显像研究

目的 评价新型心肌显像剂[99Tcm(N)(PNP=5)(DBODC)]+在猪体内的药代动力学特征及生物分布特性.方法 利用药盒法制备[99Tcm(N)(PNP5)(DBODC)]+注射液.实验动物选7头实验用成年健康中华小型猪,由耳静脉注入[99Tcm(N)(PNP5)(DBODC)]+,分别于注射后2,5,10,15,30,45,60,75,90,120,150和180 min从猪后肢静脉进行血样采集以获得药代动力学参数,同时进行胸腹部平面系列显像,以观察该药物在猪体内的生物分布和靶/非靶比值,并与99Tcm-甲氧基异丁基异腈(MIBI)显像比较(采用配对t检验).结果 [99Tcm(N)(PNP5)(DBODC)]+标记率为(95.54±0.85)%,其符合一次静脉给药的药代动力学二室模型,分布半衰期T1/2á=(2.97±0.48)min,消除半衰期T1/2a=(52.49±19.49)min,血液总清除速率(CL)=(14 314.29.±8445.79)ml/h.心、肝、肺时间-放射性曲线显示[99Tcm(N)(PNP5)(DBODC)]+肝摄取在初始时明显高于心肌,但肝内放射性清除迅速,在注射30 min后,肝内放射性已低于心肌放射性,而99Tcm-MIBI肝摄取在180 min内均高于心肌.[99Tcm(N)(PNT5)(DBODC)]+的心/肝比值在注射后30～180 min均高于99Tcm-MIBI(t值为10.395～54.482,P均＜0.05).显像示在注射[99Tcm(N)(PNP5)(DBODC)]+后5～180 min均可获得清晰的心肌图像,肝内示踪剂迅速排入胆、肠系统,致使肝内放射性迅速减低,有利于减少对左室下壁的干扰.结论 [99Tcm(N)(PNP5)(DBODC)]+有望成为一种新的心肌灌注显像剂.     

Quantitative lymphoscintigraphy using 99Tcm human serum albumin in patients with previously treated uterine cancer.

To evaluate the clinical usefulness of lymphoscintigraphy using 99Tcm human serum albumin (99Tc-HSA) in assessing lymphoedema in the lower extremities, lymphoscintigraphy was performed by subcutaneous injection of 7.4 MBq of 99Tcm-HSA in 26 patients with uterine cancer, previously treated by operation (OP) and/or radiation therapy (RT), and in five controls. Radioactivity at the injection site in the lower extremities was counted for 3 min at 10 min (A) and at 3 h (B) after injection, and clearance of 99Tcm-HSA was defined as (1-(B)/(A)) x 100(%). Clearance in controls was 46.8 +/- 3.9%, which was significantly more than those in the other treatment groups. Clearances in patients treated with both OP and RT were less than those in patients treated with either OP or RT alone (30.1 +/- 11.4 vs. 41.9 +/- 8.9, 43.7 +/- 9.6%, respectively; p less than 0.01). The clearance in legs with lymphoedema was less than those without lymphoedema in patients treated with both OP and RT (16.6 +/- 7.7 vs. 34.9 +/- 9.3%; p less than 0.01) and in patients treated with RT (33.1 +/- 7.4 vs. 48.0 +/- 5.6%; p less than 0.01). There was a significant difference between clearance in controls and clearance in non-oedematous patients' legs treated with OP and RT (p less than 0.01). In patients treated with RT alone, radiation dose was closely correlated with 99Tcm-HSA clearance and with the development of lymphoedema. These data suggest that lymphoscintigraphy using 99Tcm-HSA is useful in evaluating lymphoedema and that radiation dose is one of the factors in the development of lymphoedema.     

Comparison of technetium-99m aerosol and krypton-81m in ventilation studies for the diagnosis of pulmonary embolism

A new method of producing aerosols (technegas) in which 99Tcm is bound to carbon atoms (99Tcm-C) was evaluated by comparing 99Tcm-C images with those obtained with 81Krm in the same patients. Twenty-five patients with suspected pulmonary embolism (PE) were studied. Immediately after the last 99Tcm-C view, the patients remained in supine position and inhaled 81Krm at tidal volume. Immediately after the 81Krm ventilation views were recorded, 4-7 mCi of MAA were injected IV. The same four views (ant, lop, rop, post) were recorded after inhalation of 99Tcm-C and 81Krm (200 kcounts) and 99Tcm MAA injection (400 kcounts). The mean penetration index of 99Tcm-C (0.91) was lower than that of 81Krm (1.04) (P less than 0.03). The apex to base lung distribution of 99Tcm-C and 81Krm appeared to be similar. The mean heterogeneity of 99Tcm distribution was 23, greater than that of 81Krm (14) (P = 10(-4)). The 99Tcm-C ventilation image quality was considered very good for 16 patients and good for 6 others. Significant foci of high bronchial uptake were infrequent. Interpretation of the examinations performed after inhalation of 99Tcm-C and 81Krm was concordant in all cases. No patient had an 81Krm/99Tcm MAA examination suggestive of PE when 99Tcm-C/99Tcm MAA indicated a low probability of PE, and vice versa. 99Tcm-C aerosols enable good quality ventilation images to be obtained in nearly all cases. Thus 99Tcm-C aerosols could be used in preference to 81Krm in ventilation studies for the diagnosis of PE.