Dosimetry and biodistribution of an iodine-123-labeled somatostatin analog in patients with neuroendocrine tumors.

A modified method for the preparation of a radiolabeled analog of somatostatin (123I-octreotide) is described. The pharmacokinetics and dosimetry of this analog were evaluated in patients with neuroendocrine tumors. Thirty patients had multiple blood and urine samples and sequential anterior and posterior whole-body scintigraphy up to 40 hr postinjection of 123I-octreotide. Region of interest analysis of the whole-body images was used to determine organ and tumor doses. The 123I-octreotide was rapidly cleared from the blood with a T 1/2 of 10 min by the hepatobiliary system. By 40 hr, approximately 55% was eliminated in the feces. The gallbladder wall received the highest dose (0.48 rad/mCi), with other organs receiving doses of 0.12 rad/mCi or less. Tumors were identified in 25 of 28 satisfactory studies. Tumor doses ranged from 0.1 to 0.6 rad/mCi. Calculations with 131I instead of 123I indicated that the gallbladder wall would receive 2 rad/mCi, while average tumor doses would range from 0.9 to 5.0 rad/mCi. Iodine-123-octreotide is a useful agent for the visualization of neuroendocrine tumors. The rapid washout of this agent from tumors precludes the possibility of radiotherapy with 131I-octreotide in these patients.     

Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide.

Scintigraphy with 123I-Tyr-3-octreotide has several major drawbacks as regards its metabolic behavior, its cumbersome preparation and the short physical half-life of the radionuclide. The use of another radiolabeled analog of somatostatin, 111In-DTPA-D-Phe-1-octreotide, has consequently been proposed. DTPA-D-Phe-1-octreotide can be radiolabeled with 111In in an easy single-step procedure. DTPA-D-Phe-1-octreotide is cleared predominantly via the kidneys. Fecal excretion of radioactivity amounts to only a few percent of the administered radioactivity. For the radiation dose to normal tissues, the most important organs are the kidneys, the spleen, the urinary bladder, the liver and the remainder of the body. The calculated effective dose equivalent is 0.08 mSv/MBq. Optimal 111In-DTPA-D-Phe-1-octreotide scintigraphic imaging of various somatostatin receptor-positive tumors was obtained 24 hr after injection. In the six patients studied, tumor localization with 123I-Tyr-3-octreotide and with 111In-DTPA-D-Phe-1-octreotide were found to be similar. However, the normal pituitary is more frequently visualized with the latter radiopharmaceutical. In conclusion, 111In-DTPA-D-Phe-1-octreotide appears to be a sensitive somatostatin receptor-positive tissue-seeking radiopharmaceutical with some remarkable advantages: easy preparation, general availability, appropriate half-life and absence of major interference in the upper abdominal region, because of its renal clearance. Therefore, 111In-DTPA-D-Phe-1-octreotide may be suitable for use in SPECT of the abdomen, which is important in the localization of small endocrine gastroenteropancreatic tumors.     

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

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.     

131I]-TYR3-octreotide: clinical dosimetry and use for internal radiotherapy of metastatic paraganglioma and carcinoid tumors

Dosimetry and therapeutic application of [(131)I]-Tyr3-octreotide were evaluated in three patients with metastatic paraganglioma and carcinoid tumor. The in vitro stability of [(131)I]-Tyr3-octreotide was verified. Tumor uptake and residence time were between 0.02 and 0.1% and 0.5 to 9.8 h, respectively. The calculated tumor radiation doses were between 0.105 and 0.696 mGy.MBq(-1). No intolerance or adverse effects were observed after the therapeutic doses (3.3-6.6 GBq). A partial tumor response was obtained in one patient and no response occurred in two patients.     

[I]-TYR3-octreotide: clinical dosimetry and use for internal radiotherapy of metastatic paraganglioma and carcinoid tumors

Dosimetry and therapeutic application of [¹³¹I]-Tyr3-octreotide were evaluated in three patients with metastatic paraganglioma and carcinoid tumor. The in vitro stability of [¹³¹I]-Tyr3-octreotide was verified. Tumor uptake and residence time were between 0.02 and 0.1% and 0.5 to 9.8 h, respectively. The calculated tumor radiation doses were between 0.105 and 0.696 mGy·MBq⁻¹. No intolerance or adverse effects were observed after the therapeutic doses (3.3–6.6 GBq). A partial tumor response was obtained in one patient and no response occurred in two patients.     

Evaluation of 64Cu-labeled DOTA-d-Phe1-Tyr3-octreotide (64Cu-DOTA-TOC) for imaging somatostatin receptor-expressing tumors

Objective  In-111 (¹¹¹In)-labeled octreotide has been clinically used for imaging somatostatin receptor-positive tumors, and radiolabeled octreotide analogs for positron emission tomography (PET) have been developed. Cu-64 (⁶⁴Cu; half-life, 12.7 h) is an attractive radionuclide for PET imaging and is produced with high specific activity using a small biomedical cyclotron. The aim of this study is to produce and fundamentally examine a ⁶⁴Cu-labeled octreotide analog, ⁶⁴Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-d-Phe¹-Tyr³-octreotide (⁶⁴Cu-DOTA-TOC). Methods   ⁶⁴Cu produced using a biomedical cyclotron was reacted with DOTA-TOC for 30 min at 45°C. The stability of ⁶⁴Cu-DOTA-TOC was evaluated in vitro (incubated with serum) and in vivo (blood collected after administration) by HPLC analysis. Biodistribution studies were performed in normal mice by administration of mixed solution of ⁶⁴Cu-DOTA-TOC and ¹¹¹In-DOTA-TOC and somatostatin receptor-positive U87MG tumor-bearing mice by administration of ⁶⁴Cu-DOTA-TOC or ⁶⁴Cu-1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid-octreotide (⁶⁴Cu-TETA-OC). The tumor was imaged using ⁶⁴Cu-DOTA-TOC, ⁶⁴Cu-TETA-OC, and FDG with an animal PET scanner. Results   ⁶⁴Cu-DOTA-TOC can be produced in amounts sufficient for clinical study with high radiochemical yield. ⁶⁴Cu-DOTA-TOC was stable in vitro, but time-dependent transchelation to protein was observed after injection into mice. In biodistribution studies, the radioactivity of ⁶⁴Cu was higher than that of ¹¹¹In in all organs except kidney. In tumor-bearing mice, ⁶⁴Cu-DOTA-TOC showed a high accumulation in the tumor, and the tumor-to-blood ratio reached as high as 8.81 ± 1.17 at 6 h after administration. ⁶⁴Cu-DOTA-TOC showed significantly higher accumulation in the tumor than ⁶⁴Cu-TETA-OC. ⁶⁴Cu-DOTA-TOC PET showed a very clear image of the tumor, which was comparable to that of ¹⁸F-FDG PET and very similar to that of ⁶⁴Cu-TETA-OC. Conclusions   ⁶⁴Cu-DOTA-TOC clearly imaged a somatostatin receptor-positive tumor and seemed to be a potential PET tracer in the clinical phase.     

111In-DTPA-D-Phe1-octreotide binding and somatostatin receptor subtypes in thyroid tumors.

The purpose of this study was to evaluate the potential for therapy of thyroid tumors using the radiolabeled somatostatin (SS) analog octreotide. METHODS: Concentrations of 111In activity in human thyroid tumors and normal thyroid tissue and blood samples were determined 1-15 d after intravenous injection of 111In-diethylenetriaminepentaacetic acid-Phe1-octreotide. The results were compared with SS receptor (sstr subtype profile (by Northern blot analysis) and the relative expression of the second subtype, sstr2 (by ribonuclease protection assay, RPA). The true tumor volumes in lymph node metastases from 1 patient were estimated. In total, tissues from 68 patients were included in the study. RESULTS: The highest tumor-to-blood ratio (T/B) for medullary thyroid carcinoma (MTC) was 360; for follicular adenoma (FA), 190; for Hurthle cell adenoma (HCA), 140; and for Hurthle cell carcinoma (HCC) and papillary carcinoma (PC), 70. The corresponding value was 7-18 for normal thyroid tissue, with higher values for colloid goiter (8-48) and thyroiditis (7-120). A high T/B was related to a large fraction of tumor cells in lymph node metastases. T/Bs were higher for the tumor samples with expression of sstr2 at Northern blot analysis than for those without. All thyroid tumor types regularly expressed sstr1, sstr3, sstr4, and sstr5. sstr2 was expressed in most MTC tumors but was not detected in FA or PC and was irregularly expressed in HCA and HCC. However, RPA analysis detected sstr2 in all tumors studied. CONCLUSION: Despite the lack of sstr2 at Northern blot analysis in most of the thyroid tumors studied, high T/Bs were in general found when compared with corresponding values for normal thyroid tissue. The sometimes extremely high ratios are promising and indicate a possibility of using radiolabeled octreotide for radiation therapy of sstr-positive tumors in the future.     

Utility of thallium-201 and iodine-123 metaiodobenzylguanidine in the scintigraphic detection of neuroendocrine neoplasia

Metaiodobenzylguanidine (MIBG) is a specific marker for neuroendocrine tumours, such as phaeochromocytoma, neuroblastoma, medullary thyroid cancer (MTC) and paraganglioma, but it suffers in some cases (especially in MTC) from a lack of sensitivity. Thallium is a well-known marker of cellularity with a great sensitivity and a lack of specificity. In order to determine whether the association of these two markers is able to improve the detection of neuroendocrine lesions, 137 scintigraphic examinations using MIBG and thallium were performed in 101 patients referred for suspicion or follow-up of neuroendocrine tumours. Thallium chloride was first injected (1 MBq/kg), images being acquired about 20 min after injection; ¹²³I-MIBG (4 MBq/kg) was then injected and images acquired 5 and 24 h later. In patients with phaeochromocytoma or neuroblastoma, thallium scintigraphy appeared of little help since no tumoural site was discovered by thallium accumulation alone. In contrast, thallium examination seemed of interest in the detection of paraganglioma and MTC, the association of the two radiopharmaceuticals increasing the number of detected sites.     

Therapy using labelled somatostatin analogues: comparison of the absorbed doses with 111In-DTPA-D-Phe1-octreotide and yttrium-labelled DOTA-D-Phe1-Tyr3-octreotide

OBJECTIVE: We estimated the absorbed doses for (111)In-DTPA-D-Phe(1)-octreotide and (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide in the same patients in order to compare the potential effectiveness (tumour dose) and safety (kidney and red marrow dose) of these drugs for peptide-targeted radiotherapy of somatostatin receptor positive tumours. METHODS: Six patients with neuroendocrine tumours underwent quantitative (111)In-DTPA-D-Phe(1)-octreotide SPECT and (86)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide PET scan at intervals of 1 week. All studies were performed with a co-infusion of amino acids for renal protection. PET and SPECT were reconstructed using iterative algorithms, incorporating attenuation and scatter corrections. Tissue uptakes (IA%) were measured and used to calculate residence times. Absorbed doses to tissues were estimated and the maximal allowed activity, defined as either the activity delivering 23 Gy to the kidneys (MAA(K)) or 2 Gy to the red marrow (MAA(RM)), was calculated and the resulting tumour absorbed doses were computed. RESULTS: For the MAA(K) the mean absorbed dose to the red marrow was lower for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide than for (111)In-DTPA-D-Phe(1)-octreotide (1.8+/-0.9 Gy vs. 6.4+/-1.6 Gy; P<0.001). The median absorbed dose to tumours for the MAA(K) was two-fold higher for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide as compared to (111)In-DTPA-D-Phe(1)-octreotide (30.1 vs. 12.6 Gy; P<0.05). The median absorbed dose to tumours estimated for the MAA(RM) was 10-fold higher for (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide than for (111)In-DTPA-D-Phe(1)-octreotide (35.1 Gy vs. 3.9 Gy; P<0.05). CONCLUSIONS: This direct intra-patient comparison confirms that the use of (90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide is more appropriate for therapy of somatostatin receptor bearing tumours. When using (111)In-DTPA-D-Phe(1)-octreotide, the red marrow represents the major critical organ; this can result in significant toxicity if high activities have to be administered to obtain efficient tumour irradiation.     

Biodistribution and dosimetry of (iodine-123)-iodomethyl-N, N-diethyltamoxifen, an (anti)oestrogen receptor radioligand.

This study reports on the distribution and radiation dosimetry of iodine-123 labelled trans-Z-iodomethyl-N,N-diethyltamoxifen (123-ITX), a promising radioligand for prediction of the therapeutic efficacy of unlabelled tamoxifen in human breast carcinoma. Whole-body scans were performed up to 24 h after intravenous injection of 123-ITX (mean: 146 MBq, range: 142-148 MBq) in five female volunteers, four with and one without thyroid blockade. Blood samples were taken at various times up to 24 h after injection. Urine was also collected up to 24 h after injection, allowing calculation of renal clearance and interpretation of whole-body clearance. Time-activity curves were generated for the thyroid, heart, brain, breasts, liver and gallbladder by fitting the organ-specific geometric mean counts, obtained from regions of interest. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. The images showed rapid hepatobiliary excretion, resulting in good imaging conditions for the thoracic region, whereas imaging of the abdominal region was impeded by extensive bowel activity. The breast to non-specific uptake ratio increased over time. 123-ITX was cleared by both the kidneys and the gastrointestinal tract. At 50 h p.i. the mean excretion in the urine was 89.4% (SD 5.7%). If the thyroid was not blocked, it was one of the critical organs. The highest absorbed doses were received by the excretory organs, i.e. the urinary bladder wall, the lower and upper large intestine, and the gallbladder wall. The average effective dose of 123-ITX was estimated to be 0.0084 mSv/MBq. The amount of 123-ITX required for adequate imaging of tumoral uptake results in an acceptable effective dose to the patient.     

Technetium-99m MAG3, a comparison with iodine-123 and iodine-131 orthoiodohippurate, in patients with renal disorders

A Phase I study in 12 patients with renal disorders compared the simultaneous clearances of 99mTc-labeled mercaptoacetyltriglycine (MAG3) and 131I-labeled orthoiodohippurate (OIH). The ratio of MAG3 to OIH clearance was 0.61 +/- 0.08 as a result of its smaller volume of distribution, ratio 0.65 +/- 0.09, for the clearance half-lives were similar, ratio 1.09 +/- 0.12. A Phase II study performed serially in 20 patients with equal doses of [99mTc]MAG3 and [123I]OIH gave images of equal quality. The relative renal functions were highly correlated (r = 0.97, p less than 0.001) and transit time analyses gave good correlations: parenchymal transit time index r = 0.81, p less than 0.05. We conclude that [99mTc]MAG3 has some advantages over [99mTc]DTPA and is a suitable replacement for [123I]hippuran in routine renal imaging, relative function, and transit time studies, but not for the accurate estimation of the renal plasma flow.     

Detection of somatostatin receptor-positive tumours using the new 99mTc-tricine-HYNIC-D-Phe1-Tyr3-octreotide: first results in patients and comparison with 111In-DTPA-D-Phe1-octreotide

Indium- 111 labelled DTPA-D-Phe1-octreotide (DTPA-OC, OctreoScan) has been introduced into clinical routine for the detection of somatostatin receptor (SSTR)-positive tumours, which are predominantly of neuroendocrine origin. Potential further applications in other SSTR-positive cancers (e.g. small cell lung cancer, breast cancer, melanoma) have been limited mainly by the restricted availability and the high radionuclide costs. Previous attempts to introduce technetium-99m labelled analogues of octreotide have not been very successful in terms of the labelling procedure, in vivo biodistribution and/or tumour detection capabilities. The aim of this study was to assess the performance of the new 99mTc-labelled analogue HYNIC-D-Phe1-Tyr3-octreotide (HYNIC-TOC), using tricine as co-ligand, for the detection of SSTR-positive tumours in patients in comparison with 111In-DTPA-OC. Overall, 13 patients were examined using 99mTc-tricine-HYNIC-TOC. Twelve patients had proven SSTR-positive tumours, while one patient presented with an SSTR-negative tumour. In 9 of the 13 patients both tracers (99mTc-tricine-HYNIC-TOC and 111In-DTPA-OC) were used. Serial whole-body scans, spot views and/or single-photon emission tomography studies were performed. Images were qualitatively and semi-quantitatively (ROI analyses) evaluated. The biodistribution of 99mTc-tricine-HYNIC-TOC in patients showed high physiological uptake in kidneys, moderate uptake in liver and spleen and little uptake in the gut. The tracer showed predominantly renal and negligible hepatobiliary excretion. Known SSTR-positive tumour sites showed rapid and intense tracer accumulation. 99mTc-tricine-HYNIC-TOC demonstrated rapid tissue uptake within the first hour after injection and had basically no significant clearance (<20%) from normal or tumour tissue thereafter. In contrast, 111In-DTPA-OC showed continuous clearance from normal tissues as well as renal and very little hepatobiliary excretion. Nevertheless, the patterns of accumulation of 99mTc-tricine-HYNIC-TOC in tumours and normal organs were comparable to those of 111In-DTPA-OC. A lesion-by-lesion comparison showed comparable tumour detection capabilities in intrahepatic tumour sites and superior capabilities of 99mTc-tricine-HYNIC-TOC in respect of extrahepatic lesions. In conclusion, 99mTc-tricine-HYNIC-TOC shows promise as a tracer for SSTR imaging, given its favourable clinical characteristics (specific and high receptor affinity, good biodistribution, renal excretion, low radiation exposure, high imaging quality, on-demand availability) and cost-effectiveness. 99mTc-tricine-HYNIC-TOC allows earlier diagnosis (10 min-4 h) compared with 111In-DTPA-OC (4-24 h).     

Biodistribution and dosimetry of (iodine-123)-iodomethyl-N,N-diethyltamoxifen, an (anti)oestrogen receptor radioligand

This study reports on the distribution and radiation dosimetry of iodine-123 labelled trans-Z-iodomethyl-N,N-diethyltamoxifen (123-ITX), a promising radioligand for prediction of the therapeutic efficacy of unlabelled tamoxifen in human breast carcinoma. Whole-body scans were performed up to 24 h after intravenous injection of 123-ITX (mean: 146 MBq, range: 142–148 MBq) in five female volunteers, four with and one without thyroid blockade. Blood samples were taken at various times up to 24 h after injection. Urine was also collected up to 24 h after injection, allowing calculation of renal clearance and interpretation of whole-body clearance. Time-activity curves were generated for the thyroid, heart, brain, breasts, liver and gallbladder by fitting the organ-specific geometric mean counts, obtained from regions of interest. The MIRD formulation was applied to calculate the absorbed radiation doses for various organs. The images showed rapid hepatobiliary excretion, resulting in good imaging conditions for the thoracic region, whereas imaging of the abdominal region was impeded by extensive bowel activity. The breast to non-specific uptake ratio increased over time. 123-ITX was cleared by both the kidneys and the gastrointestinal tract. At 50 h p.i. the mean excretion in the urine was 89.4% (SD 5.7%). If the thyroid was not blocked, it was one of the critical organs. The highest absorbed doses were received by the excretory organs, i.e. the urinary bladder wall, the lower and upper large intestine, and the gallbladder wall. The average effective dose of 123-ITX was estimated to be 0.0084 mSv/MBq. The amount of 123-ITX required for adequate imaging of tumoral uptake results in an acceptable effective dose to the patient. Received 18 February and in revised form 29 April 1999     

99mTc-HYNIC-[Tyr3]-octreotide for imaging somatostatin-receptor-positive tumors: preclinical evaluation and comparison with 111In-octreotide.

In this paper we describe the preclinical evaluation of 99mTc-hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC) using different coligands for radiolabeling and a comparison of their in vitro and in vivo properties with 111In-diethylenetriaminepentaacetic acid (DTPA)-octreotide. METHODS: HYNIC-TOC was radiolabeled at high specific activities using tricine, ethylenediaminediacetic acid (EDDA), and tricine-nicotinic acid as coligand systems. Receptor binding was tested using AR42J rat pancreatic tumor cell membranes. Internalization and protein binding studies were performed, and biodistribution and tumor uptake were determined in AR42J tumor-bearing nude mice. RESULTS: All 99mTc-labeled HYNIC peptides showed retained somatostatin-receptor binding affinities (Kd < 2.65 nM). Protein binding and internalization rates were dependent on the coligand used. Specific tumor uptake between 5.8 and 9.6 percentage injected dose per gram (%ID/g) was found for the 99mTc-labeled peptides, compared with 4.3 %ID/g for 111In-DTPA-octreotide. Tricine as coligand showed higher activity levels in muscle, blood, and liver, whereas tricine-nicotinic acid produced significant levels of activity in the gastrointestinal tract. EDDA showed the most promising overall biodistribution profile, with tumor-to-liver and tumor-to-gastrointestinal tract ratios similar to those obtained with 111In-DTPA-octreotide, lower ratios in blood and muscle, but considerably higher tumor-to-kidney ratios. CONCLUSION: TOC can be radiolabeled to high specific activities using HYNIC as a bifunctional chelator. The high specific tumor uptake, rapid blood clearance, and predominantly renal excretion make 99mTc-EDDA-HYNIC-TOC a promising candidate for an alternative to 111In-DTPA-octreotide for tumor imaging.     

Serial change of iodine-123 metaiodobenzylguanidine (MIBG) myocardial concentration in patients with dilated cardiomyopathy.

Serial change of the metaiodobenzylguanidine iodine-123 (123I-MIBG) myocardial concentration was investigated in patients with dilated cardiomyopathy (DCM). Eight DCM patients and 6 control subjects were examined. After the injection of thallium-201 and 123I-MIBG, planar chest images were obtained simultaneously for both tracers in every 30-60 min over 5 h. Serial changes of myocardial uptake ratio (MUR) were compared for both tracers. In DCM, the initial MUR of 123I-MIBG did not differ significantly from that of the controls. The washout of 123I-MIBG from the myocardium, however, was significantly increased in DCM. In particular, the decrease in the early phase (15-45 min) was significantly larger in DCM than in the controls (21.2% +/- 7.5% vs. 5.3% +/- 4.0%, P less than 0.01), showing a significant negative correlation with the left ventricular ejection fraction (r = -0.72 P less than 0.05). For 201Tl, neither the initial MUR nor the washout rate different significantly between the two. Thus, an early rapid decrease of the 123I-MIBG myocardial concentration might characterize DCM and reflect the severity of this disease.     

Biokinetics of 111In-DTPA-D-Phe(1)-octreotide in nude mice transplanted with a human carcinoid tumor

The long time biokinetics of the radiolabeled somatostatin analogues 111In-DTPA-D-Phe(1)-octreotide was studied in nude mice transplanted with the human carcinoid tumor, GOT1. The results were compared with those from the patient with the original tumor. This patient has been diagnosed and later treated with 111In-DTPA-D-Phe(1)-octreotide. The animals received about 2 MBq 111In-DTPA-D-Phe(1)-octreotide (0.1 microg) by injection into a tail vein. The animals were killed 0.5 h-14 d after injection of the radiopharmaceutical. Tumor tissue and normal tissues were collected and weighed and measured for 111In activity. The 111In uptake in the tumor was higher than in all normal tissues except the kidneys. The tumor-to-normal-tissue activity concentration, TNC, increased with time for all normal tissues studied. These data were similar to those observed for the original tumor in the patient. The similar biokinetics for 111In-DTPA-D-Phe(1)-octreotide in the tumor-bearing mice and the patient makes this animal model suitable as a model for evaluation of therapy of somatostatin receptor (sstr) expressing tumors with radiolabeled somatostatin analogues. Furthermore, the increase with time of TNC both in mice and the patient indicates that long-lived radionuclides are preferred for therapy with radiolabeled somatostatin analogues.     

Correlation of chromogranin A levels and somatostatin receptor scintigraphy findings in the evaluation of metastases in carcinoid tumors

OBJECTIVE: Chromogranin A (CgA) has been gaining acceptance as a helpful tumor marker in patients with neuroendocrine tumors, with respect to both diagnosis and prognosis. The objective of this study was to correlate serum CgA levels and somatostatin receptor scintigraphy (SRS) findings in the evaluation of metastases in carcinoid tumors. MATERIALS AND METHODS: A total of 125 patients(61 men and 64 women, aged from 23 to 84 years) with histologically diagnosed carcinoid tumor underwent serum CgA assay and SRS for detecting metastasis or disease recurrence. The quantitative determination of CgA was performed in serum using an enzyme immunoassay with a cut-off value fixed at 39 U/l. Scintigraphies were performed with 200-220 MBq of In-111-DTPA-Phel-octreotide including whole-body images as well as single-photon emission computed tomography and computed tomography scans of the chest and abdomen. RESULTS: The primary tumors originated from the gastrointestinal tract in 115 of 125 patients (92.0%), the lung in 7 of 125 patients (5.6%), the kidney in 2 of 125 patients (1.6%), and the breast in 1 of 125 patients (0.8%). The primary tumors originated from the foregut, midgut, and hindgut in 13.6%, 71.2%, and 12.8%, respectively. Correlation of SRS with other imaging modalities and clinical follow-up findings revealed a sensitivity, a specificity, and an accuracy of 82.9%, 97.7%, and 88.0%, respectively, and for CgA 62.2%, 83.7%, and 69.6%, respectively. There was 1 false-positive and 14 false-negative SRS results and 7 false-positive and 31 false-negative CgA analyses. SRS demonstrated higher sensitivity, specificity, and accuracy than CgA for the evaluation of metastatic carcinoid tumors. The concordance between SRS and CgA results was 67.2%. Discrepancies, such as positive SRS with normal CgA levels, were noted in 26 (20.8%) cases, whereas negative SRS with high CgA levels was seen in 15 (12.0%) cases. Combining the results of CgA and SRS increased the sensitivity (92.7%) but decreased the specificity (81.4%) of tumor detection. CONCLUSIONS: In our study, SRS proved to be more sensitive, more specific, and more accurate than CgA for metastatic evaluation of carcinoid tumors. Positive SRS correlated with elevation of serum CgA levels. Serum CgA might have some diagnostic utility in patients with negative SRS studies. Nevertheless, both SRS and CgA should be considered useful tools in the evaluation of metastases in carcinoid patients.