Life expectancy in differentiated thyroid cancer: a novel approach to survival analysis.

In differentiated thyroid carcinoma 10-year survival rates amount to 80-95%. Because age at diagnosis varies widely, these survival rates strongly depend on age at presentation. The aim of the present study was to analyse the attributable risk factors, including therapy per se, on survival in thyroid cancer after proper adjustment for the baseline mortality rate in the general population and to elucidate the adverse treatment effects on survival. Initial treatment in 504 patients consisted of thyroidectomy and 131I ablation. High-dose 131I was administered for residual disease. Patients in complete remission underwent an annual physical examination and thyroglobulin measurements during TSH suppression. Survival time was studied after transformation to standardised survival time to adjust for the baseline mortality rate in the general population. Median follow-up since diagnosis was 9 years. The 10-year overall survival was 83% and disease-specific survival 91%. After initial treatment, persistent disease occurred in 75 patients (15%). In univariate analysis, T4, N1, M1 status and Hürthle cell type were prognostic for persistent and recurrent disease. Age was not prognostic for recurrent disease in multivariate analysis. The standardised survival time was not altered in disease-free patients. However, patients with persistent disease had a median standardised survival time of only 0.60 (95% confidence interval 0.47;0.72), ranging from 0 to above 1, independent of initial tumour status or age. The cumulative proportion of persistent disease was at least 20% of the whole group. Disease-free patients after thyroid carcinoma have a normal residual life span. In contrast, in cases of persistent disease the life expectancy ranges widely with its median being reduced to 60%. Overall, treatment including radioiodine is safe but unsuccessful in 20% of the patients. Age is not a disease-specific risk factor and should not be used as an independent factor in treatment algorithms.

Sentinel lymph node procedure is highly accurate in squamous cell carcinoma of the vulva.

PURPOSE: To determine the diagnostic accuracy of the sentinel lymph node procedure in patients with squamous cell carcinoma of the vulva and to investigate whether step sectioning and immunohistochemistry of sentinel lymph nodes increase the sensitivity for detection of metastases. PATIENTS AND METHODS: Between July 1996 and July 1999, 59 patients with primary vulvar cancer were entered onto a two-center prospective study. All patients underwent sentinel lymph node procedure with the combined technique (preoperative lymphoscintigraphy with technetium-99m-labeled nanocolloid and intraoperative blue dye). Radical excision of the primary tumor with uni- or bilateral inguinofemoral lymphadenectomy was performed subsequently. Sentinel lymph nodes and lymphadenectomy specimens were sent for histopathologic examination separately. Sentinel lymph nodes, negative at the time of routine pathologic examination, were re-examined with step sectioning and immunohistochemistry. RESULTS: In 59 patients, 107 inguinofemoral lymphadenectomies were performed (11 unilateral and 48 bilateral). All sentinel lymph nodes, as observed on preoperative lymphoscintigram, were identified successfully intraoperatively. Routine histopathologic examination showed lymph node metastases in 27 groins, all of which were detected by the sentinel lymph node procedure. The negative predictive value for a negative sentinel lymph node was 100% (97.5% confidence interval [CI], 95% to 100%). Step sectioning and immunohistochemistry showed four additional metastases in 102 sentinel lymph nodes (4%; 95% CI, 1% to 9%) that were negative at the time of routine histopathologic examination. CONCLUSION: Sentinel lymph node procedure with the combined technique is highly accurate in predicting the inguinofemoral lymph node status in patients with early-stage vulvar cancer. Future trials should focus on the safe clinical implementation of the sentinel lymph node procedure in these patients. Step sectioning and immunohistochemistry slightly increase the sensitivity of detecting metastases in sentinel lymph nodes and should be included in these trials.

No difference in cardiac event-free survival between positron emission tomography-guided and single-photon emission computed tomography-guided patient management: a prospective, randomized comparison of patients with suspicion of jeopardized myocardium.

OBJECTIVES: We sought to prospectively compare nitrogen-13 (13N)-ammonia/18fluorodeoxyglucose (18FDG) positron emission tomography (PET)-guided management with stress/rest technetium-99m (99mTc)-sestamibi single-photon emission computed tomography (SPECT)-guided management. BACKGROUND: Patients with evidence of jeopardized (i.e., ischemic or viable) myocardium may benefit from revascularization, whereas patients without it should be treated with drugs. Both PET and SPECT imaging have been proven to delineate jeopardized myocardium. When patient management is based on identification of jeopardized myocardium, it is unknown which technique is most accurate for long-term prognosis. METHODS: In a clinical setting, 103 patients considered for revascularization with left ventricular wall motion abnormalities and suspicion of jeopardized myocardium underwent both PET and SPECT imaging. The imaging results were used in a randomized fashion to determine management (percutaneous transluminal coronary angioplasty [PTCA], coronary artery bypass graft surgery [CABG] or drug treatment). Follow-up for cardiac events (cardiac death, myocardial infarction and revascularization) was recorded for 28 +/- 1 months. The study was designed to have a power of 80% to detect a 20% difference in the event rate between PET- and SPECT-based management. RESULTS: Management decisions in 49 patients randomized to PET (12 who had PTCA, 14 CABG and 23 drug therapy) were comparable with 54 patients randomized to SPECT (15 who had PTCA, 13 CABG and 26 drug therapy). In terms of cardiac event-free survival, no differences between PET and SPECT were observed (11 vs. 13 cardiac events for PET and SPECT, respectively; p = NS by the Kaplan-Meier statistic). CONCLUSIONS: No difference in patient management or cardiac event-free survival was demonstrated between management based on 13N-ammonia/18FDG PET and that based on stress/rest 99mTc-sestamibi SPECT imaging. Both techniques may be used for management of patients considered for revascularization with suspicion of jeopardized myocardium.

Imaging of soft-tissue tumors using L-3-[iodine-123]iodo-alpha-methyl-tyrosine single photon emission computed tomography: comparison with proliferative and mitotic activity, cellularity, and vascularity.

The radiolabeled amino acid L-3-[123I]-iodo-alpha-methyltyrosine (IMT) is a new tumor tracer that accumulates in many tumors and is suitable for single photon emission computed tomography (SPECT) imaging. Using IMT SPECT, we studied 32 patients with a soft-tissue tumor suspected to be a soft-tissue sarcoma to determine whether: (a) tumors can be visualized; (b) benign and malignant lesions can be distinguished; and (c) IMT uptake is related to tumor grade and proliferation. Whole-body imaging was performed 15 min after administration of 300 MBq IMT, biopsy, or resection 1-2 weeks later. IMT uptake was quantified using a region-of-interest method resulting in tumor:background (T:B) ratios. These were compared with tumor grade, mitotic index, tumor cellularity, vascularity, and the Ki-67 proliferation index. Eleven patients had a benign tumor, and 21 patients had a soft-tissue sarcoma. Six benign tumors demonstrated minor IMT uptake, and five lipomas had no uptake. All malignant tumors had high uptake and were clearly visualized. T:B ratios in malignant tumors (3.83 +/- 1.16) were higher (P < 0.001) than in benign tumors (1.52 +/- 0.60). Small (<5 mm) metastases in two patients were not detected. Taking the T:B ratio 2.0 as the cutoff level, the sensitivity for detection of malignancy was 100%, and specificity was 88%. IMT uptake correlated with histological grade (r = 0.82; P < 0.001), mitotic index (r = 0.75; P < 0.001), tumor cellularity (r = 0.73; P < 0.01), and with the Ki-67 proliferation index (r = 0.63; P < 0.01). In conclusion, IMT SPECT visualized all soft-tissue sarcomas. Uptake in sarcomas was clearly higher than in benign lesions, yielding 100% sensitivity for detection of malignancy at 88% specificity. Uptake increased with higher tumor grade and higher proliferation rate.

Phase II study of high-dose epirubicin and etoposide in advanced non-small cell lung cancer.

25 consecutive patients with advanced non-small cell lung cancer (NSCLC) were treated with high-dose epirubicin (HDE) 135 mg/m2 and etoposide 60 mg/m2 (days 1-3) every 3 weeks. 121 courses, (median 6, range 1-7), were administered and evaluable for toxicity: WHO grades III/IV leukocytopenia in 60/36 (80%) courses, thrombocytopenia in 18/6 (20%) and grades II/III anaemia in 31/6 (31%). Median (range) left ventricular ejection fraction (LVEF) fell from 63% (53-73, n = 25) to 60% (48-73 n = 16) after 5 courses (P < 0.02). 2 patients had a drop of more than 15% in LVEF with an epirubicin dose of 675 mg/m2. Apart from 1 patient who had tachycardia 6 months after the last course, no patient had congestive heart failure. There were 2 complete and 7 partial responses [total 9/25 (36%, 95% confidence interval: 18-57.5%)]. Median survival is 31.8 (4.3-75) weeks. Combination HDE and etoposide in NSCLC offers no advantage over HDE alone and is more toxic.

Radioimmunodetection of human small cell lung carcinoma xenografts in the nude rat using 111in-labelled monoclonal antibody MOC-31.

The applicability of mouse monoclonal antibody MOC-31 for in vivo radioimmunodetection of human small cell lung cancer (SCLC) was investigated in a nude rat xenograft model. MOC-31 is reactive with a 38 kD pancarcinoma membrane antigen. [111In]DTPA-MOC-31 showed good in vivo immunolocalisation to xenografted SCLC cells, whereas antigen-related uptake was low in normal rat tissues and in a control antigen-negative, human-derived tumour. Non-antigen-related uptake in the liver could be blocked by pretreatment with irrelevant antibody. It is concluded that MOC-31 can be used for radioimmunodetection of SCLC in vivo and may be suitable as a targeting device in patients.

Technetium-99m-MAG3 clearance as a parameter of effective renal plasma flow in patients with proteinuria and lowered serum albumin levels.

Although the renal clearance of 99mTc-MAG3 is about 60% of the 131I-hippurate clearance, 99mTc-MAG3 clearance may be useful to estimate ERPF. In one study, however, proteinuria seemed to influence the MAG3/hippurate clearance ratio. In order to establish whether proteinuria or serum albumin level has influence on this ratio, a comparison was made between 99mTc-MAG3 clearance and 131I-hippurate clearance in 14 patients. There was a good linear correlation between MAG3 and hippurate clearance, although the standard error of estimate of ERPF from MAG3 was relatively large, which remained unexplained. No correlation was found between proteinuria and MAG3/hippurate clearance ratio nor between serum albumin level, GFR, FF, ERPF and the MAG3/hippurate clearance ratio. We therefore conclude that there is no correlation between proteinuria and albumin level and the MAG3/hippurate ratio. A reasonable estimation of ERPF with MAG3 can be made in patients with proteinuria and lowered serum albumin levels although the estimation may be less accurate.

Meta-[I-131]iodobenzylguanidine uptake in a nonsecreting paraganglioma.

In a patient with a paraganglioma at the carotid bifurcation, intense uptake of meta-[I-131]iodobenzylguanidine (I-131 MIBG) in the tumor was found. There was no clinical or biochemical evidence for catecholamine secretion by the tumor, although analysis of the tissue revealed that catecholamine biosynthesis took place. We conclude that accumulation of I-131 MIBG may occur in a paraganglioma, but does not necessarily indicate endocrine activity of the tumor.

Esophageal hypomotility in primary and secondary Raynaud's phenomenon: comparison of esophageal scintigraphy with manometry.

UNLABELLED: Esophageal motility was assessed by manometry and scintigraphy in 25 patients with primary Raynaud's phenomenon and 24 patients with secondary Raynaud's phenomenon as part of a connective tissue disorder. METHODS: For each scintigraphic study, transit time was evaluated after three separate swallows. Scintigraphy was abnormal if transit time was longer than 15 sec for two or three measurements. RESULTS: In the case of primary Raynaud's phenomenon, manometry was normal in 24 of 25 patients. A similar ratio was found with scintigraphy. In the case of secondary Raynaud's phenomenon manometry was abnormal in 15 of 24 patients, while scintigraphy was abnormal in 13 of 24 patients. Considering manometry as gold standard, overall sensitivity of scintigraphy was 86%, specificity 89%, positive predictive value 75% and negative predictive value 94%. CONCLUSION: Esophageal dysfunction is common in patients with connective tissue disorders but rare in patients with primary Raynaud's phenomenon. Esophageal scintigraphy is a useful noninvasive initial screening test for esophageal dysfunction in patients with Raynaud's phenomenon.

Diagnostic use of angiotensin converting enzyme inhibitors in radioisotope evaluation of unilateral renal artery stenosis.

Iodine-123 hippurate renography, [99mTc]diethylenetriaminepentaacetic acid (DTPA) renography, and [99mTc]dimercapto succinic acid (DMSA) renal scintigraphy were performed before and during angiotensin converting enzyme (ACE) inhibition in a group of 15 hypertensive patients with angiographically "significant" unilateral renal artery stenosis. Visual and quantitative evaluation of the three radioisotope methods before ACE inhibition already disclosed abnormalities suggestive of renal artery stenosis in a high percentage (87%, 60%, and 60%, respectively) in this group of patients, but ACE inhibition further improved the diagnostic yield in all three methods (93%, 86%, and 80%). Iodine-123 hippurate renography was at least as useful as [99mTc]DTPA renography in this respect, while [99mTc]DMSA scintigraphy can be used particularly in segmental stenosis. Despite a large drop in blood pressure after ACE inhibition little adverse reactions were seen and overall renal function was fairly well maintained, the exceptions noted in patients with initially a more impaired renal function.

Renal handling of technetium-99m DMSA: evidence for glomerular filtration and peritubular uptake.

The finding of an enhanced excretion of [99mTc]dimercaptosuccinic acid (DMSA) in patients with tubular reabsorption disorders prompted us to investigate the role of filtration in the renal handling of [99mTc]DMSA. Our studies in human serum indicated that binding to serum proteins was approximately 90%. Chromatography of human urine and studies in rats showed that the complex was excreted unaltered into the urine. Renal extraction of [99mTc]DMSA in a human volunteer was 5.8%. Continuous infusion of [99mTc]DMSA in 13 individuals with normal renal function gave the following results (mean +/- s.d.): plasma clearance of [99mTc]DMSA 34 +/- 4 ml/min, urinary clearance of [99mTc]DMSA 12 +/- 3 ml/min. The calculated filtered load of [99mTc]DMSA closely resembled the urinary clearance, whereas the plasma clearance was about three times faster. This indicates that peritubular uptake accounts for approximately 65% and filtration for approximately 35% of the renal handling of [99mTc]DMSA.

Angiotensin-converting enzyme inhibition-induced changes in hippurate renography and renal function in renovascular hypertension.

UNLABELLED: We studied the mechanism of angiotensin-converting enzyme (ACE) inhibition-induced changes in hippurate renography of the poststenotic kidney. METHODS: Ten male mongrel dogs, six with unilateral and four with bilateral renal artery stenosis, were equipped with renal artery blood flow probes and catheters in the aorta, atrium and both renal veins. RESULTS: Enalaprilat (10 mg intravenously) in conscious dogs with renal artery stenoses produced changes in all stenotic (n = 11) but not in nonstenotic kidney 123I-hippurate renograms (n = 6). Renographic changes correlated significantly with initiation of intrarenal 131I-hippurate retention, a decrease in mean arterial pressure (MAP), renal extraction of 131I-hippurate and 125I-iothalamate (r = 0.68, r = 0.62, r = 0.84, r = 0.83, respectively) but not with renal blood flow changes (r = 0.34). Furthermore, renal uptake of 131I-hippurate and 125I-iothalamate decreased in stenotic kidneys with a grade II renogram (-52 +/- 11% and -79 +/- 6%, respectively). Iodine-125-hippurate autoradiograms of stenotic kidneys during ACE inhibition showed tracer retention mainly in the proximal tubular cells. Results during osmotic diuresis supported our findings. CONCLUSION: Angiotensin-converting enzyme inhibition-induced hippurate retention curves of poststenotic kidneys appear to result from a sequence of events. A decrease in MAP combined with efferent vasodilation leads to a decrease in intraglomerular capillary pressure. This decrease in pressure causes a decrease in glomerular filtration rate and proximal tubular urine flow. This decrease in turn hampers tubular hippurate transit and transport across the luminal membrane, leading to intrarenal hippurate retention and, in more severe cases, decreased renal hippurate uptake.

L-3-[123I]Iodo-alpha-methyltyrosine scintigraphy in carcinoid tumors: correlation with biochemical activity and comparison with [111In-DTPA-D-Phe1]-octreotide imaging.

UNLABELLED: Carcinoid tumors can produce serotonin (5-hydroxytryptamine) and catecholamines from the precursors tryptophan and tyrosine. Our aim was to evaluate the tyrosine analog L-3-[123I]iodo-alpha-methyltyrosine (IMT) in the detection and the determination of biochemical activity of these tumors in comparison with 111In-labeled [diethylenetriaminepentaacetic acid (DTPA)-D-Phe1]-octreotide (111In-octreotide) scintigraphy. METHODS: SPECT and planar whole-body imaging were performed 15 min after administration of 300 MBq IMT in 22 patients with metastatic carcinoid tumors. The number of lesions detected was compared with the number detected by 111In-octreotide scintigraphy. The size and intensity of uptake of all lesions were graded using a simple scoring system, yielding a total body uptake score for both tracers. These scores were compared (nonparametric correlation) with biochemical markers of serotonin and catecholamine metabolism. RESULTS: IMT SPECT detected only 63 of 145 lesions detected by 111In-octreotide imaging (43%). IMT SPECT performance was best in the liver (60% detection rate). Both IMT uptake and 111In-octreotide uptake scores correlated with markers of serotonin metabolism (respective values for urinary 5-hydroxyindoleacetic acid: r = 0.67 and 0.48, P < 0.001 and 0.05; for urinary serotonin: r = 0.56 and 0.40, P = 0.002 and 0.05; and for platelet serotonin: r = 0.57 and 0.45, P < 0.01 and 0.05). No correlation with adrenaline or noradrenaline metabolites was found. However, IMT uptake, but not 111In-octreotide uptake, correlated with dopamine metabolite excretion (homovanillic acid: r = 0.60, P < 0.05; and dopamine relative sum: r = 0.61, P < 0.05). IMT uptake was higher in patients with increased dopamine metabolite excretion (P = 0.05). CONCLUSION: IMT uptake can be demonstrated in carcinoid lesions, but the method detected only 43% of carcinoid lesions that were positive on 111In-octreotide scintigraphy. Uptake of both tracers is related to the serotonin secretory activity. However, IMT uptake, but not 111In-octreotide uptake, was related to tumor dopamine metabolism. These findings may be of interest in the metabolic targeting of carcinoids.

Kinetic studies with iodine-123-labeled serum amyloid P component in patients with systemic AA and AL amyloidosis and assessment of clinical value.

UNLABELLED: In systemic amyloidosis, widespread amyloid deposition interferes with organ function, frequently with fatal consequences. Diagnosis rests on demonstrating amyloid deposits in the tissues, traditionally with histology although scintigraphic imaging with radiolabeled serum amyloid P component (SAP) has lately been developed as a specific noninvasive alternative. We report a detailed analysis of the abnormal turnover of SAP in patients with systemic amyloidosis and an assessment of its clinical value. METHODS: Iodine-123-labeled human SAP (200 MBq) SAP was injected intravenously into 49 patients with histologically proven systemic AA- or AL- amyloidosis and in 7 control subjects. Plasma clearance and whole-body retention of labeled SAP were analyzed over 48 hr using plasma sampling, whole-body gamma camera imaging and measurement of radioactivity in the urine. The rate of SAP synthesis and interstitial exchange were determined, and the size of the amyloid compartment was compared with clinical estimates of whole-body amyloid load and patient survival. RESULTS: All plasma time-activity curves were biphasic. In comparison with control subjects, patients with amyloidosis showed significantly faster plasma disappearance [4-hr value: AA 48% +/- 18%, AL 45% +/- 15% versus 65% +/- 8% (p < 0.05)], higher total-body retention 48 hr p.i. [AA 74% +/- 14%, AL 73% +/- 17% versus 46% +/- 15% (p < 0.01)] and especially higher extravascular retention 48 hr p.i. [AA 59% +/- 16%, AL 58% +/- 19% versus 30% +/- 14% (p < 0.01)]. Extravascular retention correlated with clinical estimation of the amyloid load. If extravascular retention values in patients with AL amyloidosis were over 60%, survival was decreased (median 4 versus 23 mo, p < 0.001). Markedly increased interstitial exchange rates were present in amyloidosis (AA 64 +/- 61, AL 50 +/- 37 versus 18 +/- 8 mg/hr), whereas the SAP synthesis rate did not differ from the control values (AA 5.0 +/- 3.0, AL 5.5 +/- 3.2 versus 4.5 +/- 1.4 mg/hr). CONCLUSION: The presence of systemic amyloidosis is characterized by accelerated initial clearance of 123I-SAP from the plasma and increased interstitial exchange rate and extravascular retention. These findings reflect reversible binding of radiolabeled SAP to amyloid deposits and provide clinically useful information for diagnosis, monitoring of therapy and prognosis in patients with systemic amyloidosis.

Sentinel lymph node identification with technetium-99m-labeled nanocolloid in squamous cell cancer of the vulva.

UNLABELLED: In patients with early-stage squamous cell cancer of the vulva, inguinofemoral lymphadenectomy is performed primarily as a diagnostic procedure. The morbidity of this procedure, however, is not negligible. The aim of this study was to evaluate the feasibility of minimally invasive detection of the sentinel inguinofemoral lymph node (SILN) and to investigate whether the histopathology of the SILNs is representative of that of the other non-SILNs. METHODS: Patients with early-stage squamous cell cancer of the vulva, planned for resection of the primary tumor and uni- or bilateral inguinofemoral lymphadenectomy, were eligible for the study. Technetium-99m-labeled nanocolloid was injected intradermally at four locations around the tumor the day before operation. Images were recorded immediately and after 2.5 hr using a gamma camera. SILN locations were marked on the overlying groin skin. The next day, during general anesthesia, blue patent dye was injected intradermally at the same locations around the tumor. During the operation SILNs were identified at the place indicated using a handheld gamma-detection probe. It was noted if SILNs were found by the probe, by blue dye or by both techniques. After resection of the SILNs, a standard inguinofemoral lymphadenectomy was performed. The results of histopathology of the SILNs were compared with those of the non-SILNs. RESULTS: The procedure was well tolerated by 10 of 11 patients. One patient, initially agreeing to participate, refused the injection of tracer because of fear of pain. In all 10 patients, identification of the SILNs was successful. The mean time for identification was 11 min. Identification of SILNs was primarily performed using the hand probe in all patients, whereas in 10 of 18 removed SILNs afferent lymph channels were also blue stained (56%). In 8 patients, pathologic examination showed no metastatic disease in both SILNs and non-SILNs, whereas in 2 patients metastases in the SILNs (one and two metastatic lymph nodes, respectively), as well as in other non-SILNs, were found. CONCLUSION: This study shows that identification of SILNs in squamous cell cancer of the vulva is feasible with preoperatively administered 99mTc-labeled nanocolloid. Intraoperatively administered blue dye was only useful for confirmation of identification with nanocolloid. To date, no false-negative SILNs have been found, but expansion of the study is necessary to determine the possible clinical application of this new diagnostic technique.

Radiolabeled amino acids: basic aspects and clinical applications in oncology.

As the applications of metabolic imaging are expanding, radiolabeled amino acids may gain increased clinical interest. This review first describes the basic aspects of amino acid metabolism, then continues with basic aspects of radiolabeled amino acids, and finally describes clinical applications, with an emphasis on diagnostic value. A special focus is on (11)C-methionine, (11)C-tyrosine, and (123)I-iodomethyltyrosine, because these have been most used clinically, although their common affinity for the L-transport systems may limit generalization to other classes of amino acids. The theoretic and preclinical background of amino acid imaging is sound and supports clinical applications. The fact that amino acid imaging is less influenced by inflammation may be advantageous in comparison with (18)F-FDG PET imaging, although tumor specificity is not absolute. In brain tumor imaging, the use of radiolabeled amino acids is established, the diagnostic accuracy of amino acid imaging seems adequate, and the diagnostic value seems advantageous. The general feasibility of amino acid imaging in other tumor types has sufficiently been shown, but more research is required in larger patient series and in well-defined clinical settings.

L-3-[123I]iodo-alpha-methyl-tyrosine SPECT in non-small cell lung cancer: preliminary observations.

UNLABELLED: L-3-[123I]iodo-alpha-methyl-tyrosine (IMT) is a modified amino acid that is avidly taken up by many tumors. Uptake is based on the increased transmembrane transport of amino acids in malignancies. IMT is the only amino acid tracer suitable for SPECT. The aim of this study was to determine the feasibility of IMT SPECT in the detection, staging, and treatment evaluation of non-small cell lung cancer. METHODS: We evaluated 44 IMT SPECT studies in 17 patients with histologically proven non-small cell lung cancer, stage III. IMT SPECT and planar imaging of the chest was performed before, 2 wk after, and 3 mo after 60 Gy radiotherapy. Staging was based on the findings of bronchoscopy, chest CT, mediastinoscopy, or explorative thoracotomy. After radiotherapy, CT and bronchoscopy were repeated to assess tumor response. RESULTS: In 15 of 16 evaluable primary tumors, avid IMT uptake was present (sensitivity, 94%), with a mean (+/-SD) tumor-to-background ratio (T/B) of 2.95 +/- 0.78 (range, 1.7-4.9). In 12 of 14 patients (86%) with mediastinal involvement, IMT SPECT detected one or more mediastinal metastases. However, only 13 of 20 mediastinal metastases were detected in lesion analysis (lesion-based sensitivity, 65%). For lesions < 2 cm in diameter, sensitivity was 42%. FDG PET (available for 5 patients) detected more known and unknown lesions than did IMT SPECT. After radiotherapy, T/B had fallen to 1.84 +/- 0.29 (P < 0.001 vs. baseline), and 3 mo later to 1.61 +/- 0.41 (not statistically significant vs. second study). Considerable nonspecific uptake was found in irradiated normal lung tissue (mean ratio to nonirradiated tissue, 1.79 +/- 0.53), persisting for > 3 mo. No relationship was observed between various IMT uptake parameters and the presence of residual viable tumor tissue or survival. CONCLUSION: IMT SPECT has a high sensitivity for the detection of primary non-small cell lung cancer. Although patient-based sensitivity in detecting mediastinal spread was adequate, sensitivity for individual lesions, especially for small metastases (<2 cm in diameter) was too low to be clinically helpful. Radiotherapy caused considerable nonspecific IMT uptake, which also limits applicability in evaluating the results of treatment.

Pharmacokinetics and scintigraphy of indium-111-DTPA-MOC-31 in small-cell lung carcinoma.

UNLABELLED: Radiolabeled MOC-31 retains its immunoreactivity and shows good in vivo immunolocalization to human SCLC xenografted in nude rats. METHODS: We evaluated the immunotargeting properties and safety of 111In-labeled monoclonal antibody (MAb) MOC-31 (125 MBq, 5 mg) in six patients with histologically proven small-cell lung cancer (SCLC). Scintigraphy and pharmacokinetics were performed up to 3 days after injection. RESULTS: No adverse reactions were found after injection of MAb MOC-31. Pharmacokinetics obtained from plasma radioactivity showed plasma disappearance described most properly by a monoexponential model with a mean half-life value of 17.0 +/- 1.4 hr. HPLC analysis documented the monomeric MOC-31 without evidence of immune complexes or radioactive lower molecular weight fractions. Mean 24-hr urinary excretion of radioactivity was 4.3% of the injected dose. Scintigraphy detected primary tumor or metastases in five of six patients. Localization of radioactivity in normal tissue was restricted, but additional experiments need to be performed to elucidate possible cross-reactivity of MOC-31 with normal tissue in vivo. CONCLUSION: Preliminary results justify further studies to reveal the possible usefullness of radiolabeled MOC-31 in the therapeutic and diagnostic management of SCLC.

Feasibility of tumor imaging using L-3-[iodine-123]-iodo-alpha-methyl-tyrosine in extracranial tumors.

UNLABELLED: L-3-[123I]-Iodo-alpha-methyl-tyrosine (IMT) is a modified amino acid. It is reported to be avidly taken up in brain tumors, reflecting amino acid transport and is suitable for SPECT. METHODS: To determine whether tumors outside the brain can also accumulate this tracer, we injected 300-450 MBq IMT into 20 patients with different tumors [5 breast cancers, 4 lung tumors (1 benign), 2 carcinoid liver metastases, 4 soft-tissue tumors (1 benign), 3 malignant lymphomas and 2 primary brain tumors]. Tumor size ranged from 1-12 cm. Imaging was repeated after radiotherapy in two patients with breast cancer. Histology was available in all cases. Dynamic scans, whole-body imaging and SPECT were performed during the first hour and 3 hr after injection. Plasma samples were analyzed for IMT, free 1231 and other metabolites. RESULTS: All primary tumors were visualized. Tumor-to-background ratios ranged from 1.1 to 3.8 on planar and from 1.3 to 6.2 on SPECT images. Tumor uptake peaked in the first hour. Two carcinoid lesions in the liver tumors exhibited no IMT uptake above liver background. Tumor-to-background ratios in a benign bone inflammatory process and a focal pulmonary vasculitis were less than 1.2 (planar) and 1.9 (SPECT) and could be differentiated from uptake in all malignant nonbrain tumors. IMT was rapidly cleared from the plasma [3.6% +/- 0.6% (mean +/- s.d.) injected dose/liter at 10 min postinjection]. Minor in vivo deiodination was present (<1% of injected dose 1 hr postinjection). No other metabolites were found. Normal distribution consists of some uptake in the brain, liver, spleen, muscles, pancreatic region and intestinal structures and massive uptake and excretion in the kidneys and bladder. CONCLUSION: IMT has potential as a metabolic tracer in tumors outside the brain.

Sentinel node biopsy as a surgical staging method for solid cancers.

The sentinel node is the first lymph node that drains a primary tumour. If this lymphatic drainage occurs in a step-wise fashion, this lymph node reflects the pathological status of the remaining lymph node basin. The day before the operation, a total dose of 60 MBq 99mTc nanocolloid is injected around the primary tumour for lymphoscintigraphy. On the day of surgery, 1 ml of blue dye is injected around the primary tumour to facilitate sentinel lymph node detection. After making a small incision over the regional lymph node region, the sentinel node can be detected using a hand-held gamma ray detection probe; the sentinel lymph node and the afferent lymphatic vessels will be stained blue. Sentinel node biopsy has proved useful for malignant melanoma, breast cancer, penile cancer, vulvar cancer, Merkel cell carcinoma and thyroid cancer. New studies are described on breast cancer and malignant melanoma. Gamma-probe-guided localization of radiolabelled lymph nodes can direct the surgeon non-invasively to the exact location of the sentinel node. Once localized with a gamma probe, it is quick and easy to remove the sentinel node through a small incision. Discriminating the node from other tissue can be aided by blue dye which stains the lymph node. It appears that both radioactivity and blue dye are complementary for locating the sentinel node.