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Data on the efficacy of excimer laser coronary atherectomy (ELCA) for patients with ST-elevation myocardial infarction (STEMI) are limited. Therefore, we sought to evaluate the impact of ELCA on myocardial salvage using nuclear scintigraphy in patients with STEMI. Between September 2014 and April 2017, we retrospectively enrolled 316 consecutive patients undergoing primary PCI (p-PCI) after their first STEMI in our institute. Of those, 72 patients with STEMI, an initial thrombolysis in myocardial infarction (TIMI) flow-0/1, and an onset to balloon time (OBT) < 6 h were included (ELCA, n = 32; non-ELCA, n = 40). The endpoint was the myocardial salvage index (MSI) based on a 17-segment model with a 5-point scoring system. MSI was calculated as: MSI = (∑ 123 I-BMIPP defect score at 3-7 days after p-PCI - ∑ 99m Tc-tetrofosmin defect score at 3-6 months after p-PCI)/∑ 123 I-BMIPP defect score × 100 (%) at 3-7 days after p-PCI. The groups were compatible except in age (ELCA: 62.9 ± 12.4 years vs. non-ELCA: 69.8 ± 11.0 years) and loading antiplatelet drug (prasugrel: 100% vs. 40.0%). Direct implantation of shorter stents more frequently occurred in the ELCA group than in the non-ELCA group. MSI seemed to be better in the ELCA group compared with the non-ELCA group (57.6% vs. 45.6%, p = 0.09). This trend was emphasized when the final TIMI-3 flow was achieved (67.1% vs. 45.7%, p = 0.01). The nuclear scintigraphy results showed that ELCA can potentially improve myocardial salvage in patients with STEMI with OBT < 6 h and initial TIMI flow-0/1.

Aim: This study investigated the prognostic factors of cardiac death or cardiac failure using cardiac scintigraphy, echocardiography (UCG), and magnetic resonance imaging (MRI) in asymptomatic systemic sclerosis (SSc) patients., Methods: We retrospectively evaluated SSc patients who had undergone cardiac scintigraphy using 99m thallium ( 99m Tl) and 123 I-β-methyl-P-iodophenyl-pentadecanoic acid ( 123 I-BMIPP), UCG, and cardiac MRI. We calculated the mismatch score in scintigraphy by subtracting the uptake of 123 I-BMIPP from that of 99m Tl. Patients were divided into two groups according to whether they survived with no cardiac failure or subsequently proceeded to cardiac failure or death during the study period. We identified prognostic factors by analyzing 99m Tl and 123 I-BMIPP uptake, mismatch scores, UCG findings, and cardiac delayed enhancement on MRI. We also evaluated pathological evidence of myocardial fibrosis., Results: Of 33 SSc cases, 11 proceeded to cardiac failure or death. There was no significant difference in UCG or MRI findings between the two groups. Low mismatch score in cardiac scintigraphy was the only predictive factor of cardiac failure or death by multivariate analysis (odds ratio, 6.48; 95% confidence interval, 1.22-423.2; P = 0.01). When patients were grouped according to high or low mismatch scores based on a cut-off using receiver operating characteristics curve analysis, the cumulative incidence of cardiac failure or death was higher in the low mismatch group than in the high mismatch group (P = 0.02). The percentage of fibrosis was significantly higher in deceased cases compared to surviving cases., Conclusions: Low mismatch score in cardiac scintigraphy was associated with cardiac death or cardiac failure in SSc patients., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Introduction: CLR1404 is a theranostic molecular agent that can be radiolabeled with 124 I (CLR 124) for positron emission tomography (PET) imaging, or 131 I (CLR 131) for single-photon emission computed tomography (SPECT) imaging and targeted radionuclide therapy. This pilot study evaluated a pretreatment dosimetry methodology in a triple-negative breast cancer patient who was uniquely enrolled in both a CLR 124 PET imaging clinical trial and a CLR 131 therapeutic dose escalation clinical trial., Materials and Methods: Three-dimensional PET/CT images were acquired at 1, 3, 24, 48, and 120 h postinjection of 178 MBq CLR 124. One month later, pretherapy 2D whole-body planar images were acquired at 0.25, 5, 24, 48, and 144 h postinjection of 370 MBq CLR 131. Following the therapeutic administration of 1990 MBq CLR 131, 3D SPECT/CT images were acquired at 74, 147, 334, and 505 h postinjection. The therapeutic CLR 131 voxel-level absorbed dose was estimated from PET (RAPID PET) and SPECT (RAPID SPECT) images using a Geant4-based Monte Carlo dosimetry platform called RAPID (Radiopharmaceutical Assessment Platform for Internal Dosimetry), and region of interest (ROI) mean doses were also estimated using the OLINDA/EXM software based on PET (OLINDA PET), SPECT (OLINDA SPECT), and planar (OLINDA planar) images., Results: The RAPID PET and OLINDA PET tracer-predicted ROI mean doses correlated well (m ≥ 0.631, R 2 ≥ 0.694, p ≤ 0.01) with both the RAPID SPECT and OLINDA SPECT therapeutic mean doses. The 2D planar images did not have any significant correlations. The ROI mean doses differed by -4% to -43% between RAPID and OLINDA/EXM, and by -19% to 29% between PET and SPECT. The 3D dose distributions and dose volume histograms calculated with RAPID were similar for the PET/CT and SPECT/CT., Conclusions: This pilot study demonstrated that CLR 124 pretreatment PET images can be used to predict CLR 131 3D therapeutic dosimetry better than CLR 131 2D planar images. In addition, unlike OLINDA/EXM, Monte Carlo dosimetry methods were capable of accurately predicting dose heterogeneity, which is important for predicting dose-response relationships and clinical outcomes.

To inhibit both the local and systemic complications with acute pancreatitis, an effective therapy requires a drug delivery system that can efficiently overcome the blood-pancreas barrier while achieving lung-specific accumulation. Here, we report the first dual pancreas- and lung-targeting therapeutic strategy mediated by a phenolic propanediamine moiety for the treatment of acute pancreatitis. Using the proposed dual-targeting ligand, an anti-inflammatory compound Rhein has been tailored to preferentially accumulate in the pancreas and lungs with rapid distribution kinetics, excellent tissue-penetrating properties and minimum toxicity. Accordingly, the drug-ligand conjugate remarkably downregulated the proinflammatory cytokines in the target organs thus effectively inhibiting local pancreatic and systemic inflammation in rats. The dual-specific targeting therapeutic strategy may help pave the way for targeted drug delivery to treat complicated inflammatory diseases., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Myocardial injury can be detected more sensitively using (123)I-radioiodinated 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) than thallium-201 (TL). The present study investigated whether (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) uptake as an index of active inflammation in patients with cardiac sarcoidosis (CS) is associated with BMIPP and TL findings, and whether dual single-photon emission computed tomography (SPECT) can facilitate diagnosis of CS., Methods and results: We retrospectively enrolled 52 consecutive patients with suspected CS who were assessed on FDG-PET/computed tomography (CT) and BMIPP/TL dual SPECT. The SPECT images were divided into 17 segments and then BMIPP and TL total defect scores (BMDS, TLDS) as well as mismatch scores (BMDS-TLDS: sumMS) were calculated. Maximum standardized uptake value (SUVmax) in the entire myocardium was obtained from FDG-PET/CT. SUVmax was much higher in patients with, than without CS (P<0.0001). BMDS was higher and sumMS much higher in CS (P<0.05 and P<0.0001, respectively). The sensitivity and specificity of sumMS to detect CS were 74% and 80%, respectively. SUVmax was not associated with either BMDS or sumMS in the patients with CS. On multivariate analysis, the combination of sumMS and SUVmax had greater prognostic significance compared with each parameter on its own., Conclusions: BMIPP and TL dual-tracer mismatch is a useful finding to diagnose CS, and adds greater diagnostic value to SUVmax on FDG-PET/CT.

This study explores the imaging and therapeutic properties of a novel radiopharmaceutical, (131)I-CLR1404. Phase 1a data demonstrated safety and tumor localization by SPECT-CT. This 1b study assessed safety, imaging characteristics, and possible antineoplastic properties and provided further proof-of-concept of phospholipid ether analogues' retention within tumors. A total of 10 patients received (131)I-CLR1404 in an adaptive dose-escalation design. Imaging characteristics were consistent with prior studies, showing tumor uptake in primary tumors and metastases. At doses of 31.25 mCi/m(2) and greater, DLTs were thrombocytopenia and neutropenia. Disease-specific studies are underway to identify cancers most likely to benefit from (131)I-CLR1404 monotherapy.

Background: (18)F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) is assumed to be the most useful method for evaluating the viability of the myocardium. However, there are few reports regarding serial changes in (18)F-FDG-PET images of acute myocardial infarction (AMI). We evaluated serial changes in glucose-loaded (18)F-FDG-PET, (123)I-β-methyl-p-iodophenyl-penta-decanoic acid (BMIPP) single-photon emission computed tomography (SPECT) and (99m)Tc-Tetrofosmin (TF) gated SPECT images in patients with AMI., Methods and Results: We enrolled 7 consecutive patients with first anterior AMI who successfully underwent percutaneous coronary intervention (PCI). (18)F-FDG-PET images were obtained in the acute, subacute, chronic, mid-term and long-term phases. (123)I-BMIPP and (99m)Tc-TF SPECT images were obtained in the subacute, chronic, mid-term and long-term phases. We determined the total defect score (TDS) for each image. The TDS of the glucose-loaded (18)F-FDG-PET, (123)I-BMIPP and( 99m)Tc-TF SPECT images indicated significant serial decrease (P<0.001). Comparing these images, the TDS of the glucose-loaded (18)F-FDG-PET images was larger than that of the (123)I-BMIPP and (99m)Tc-TF SPECT images, and the TDS indicated (18)F-FDG-PET>(123)I-BMIPP>(99m)Tc-TF in all phases., Conclusions: The defect areas of glucose-loaded (18)F-FDG-PET images were significantly larger than those of (123)I-BMIPP and( 99m)Tc-TF SPECT images during 9 months follow-up of patients with successful PCI for anterior AMI. Additionally, the impairment of glucose metabolism was prolonged.

Background: Because of their high risk for cardiovascular events, we investigated the role of (123)I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) SPECT in evaluating the prognosis of diabetic patients with suspected coronary heart disease., Methods and Results: We retrospectively registered 186 diabetic patients with suspected coronary heart disease, but no previous diagnosis of heart disease, who had been examined by BMIPP and thallium (TL) dual SPECT. They were followed for over 2 years. The dual SPECT images were scored to obtain summed defect scores for each SPECT image (BMDS, TLDS and mismatch score [MS]). The primary endpoint was the first incidence of all-cause cardiac events. The secondary endpoint was cardiac death. Clinical classical risk factors in addition to the stage of chronic kidney disease (CKD), as well as cardiac function, were included in the prognostic analysis. Cardiac events occurred in 39 patients, including 8 cardiac deaths. Kaplan-Meier analysis revealed significantly more frequent cardiac event rates in patients with than without MS ≥5 or BMDS ≥6 (P<0.0001). Cox hazard multivariate analysis showed that MS and CKD stage or BMIPP and CKD stage were independent predictors. Only hemodialysis was a significant prognostic indicator for cardiac death., Conclusions: BMIPP SPECT when combined with CKD stage accurately predicts cardiac events among diabetic patients with suspected ischemic heart disease.

A 12 yr old castrated male Yorkshire terrier was presented with a history of an inoperable pheochromocytoma. Physical examination revealed a large, midabdominal mass. Neurologic examination was normal at presentation. An abdominal computed tomography scan revealed a 215 cm(3) mass in the region of the right kidney. Forty-eight hours after IV injection of 370 megabecquerels (MBq, equivalent to10 millicuries [mCi]) of metaiodobenzylguanidine labeled with radioactive iodine ([(131)I]MIBG), standard planar scintigraphy was performed. A diffuse area of moderate uptake was noted in the midabdominal region. The dog experienced stable disease for 1.5 mo after injection based on a follow-up computed tomography (CT) scan; however, 5 mo after injection, repeat CT imaging revealed progression of the tumor, and a second IV injection of 370 MBq (10 mCi) of [(131)I]MIBG was administered. The dog died 3 wk after the second injection as a result of gastrointestinal blood loss that was believed to be caused by compression-induced bowel ischemia by the mass. A full necropsy was not performed, but the mass was removed for histologic evaluation, which confirmed the diagnosis of pheochromocytoma. This report is the first to document the treatment of canine pheochromocytoma using [(131)I]MIBG.

Simultaneous rest perfusion/fatty-acid metabolism studies have the potential to replace sequential rest/stress perfusion studies for the assessment of cardiac function. Simultaneous acquisition has the benefits of increased signal and lack of need for patient stress, but is complicated by cross-talk between the two radionuclide signals. We consider a simultaneous rest (99m)Tc-sestamibi/(123)I-BMIPP imaging protocol in place of the commonly used sequential rest/stress (99m)Tc-sestamibi protocol. The theoretical precision with which the severity of a cardiac defect and the transmural extent of infarct can be measured is computed for simultaneous and sequential SPECT imaging, and their performance is compared for discriminating (1) degrees of defect severity and (2) sub-endocardial from transmural defects. We consider cardiac infarcts for which reduced perfusion and metabolism are observed. From an information perspective, simultaneous imaging is found to yield comparable or improved performance compared with sequential imaging for discriminating both severity of defect and transmural extent of infarct, for three defects of differing location and size.

Our purpose was to evaluate the effects of exercise intensities on free fatty acid (FFA) uptake in skeletal muscles, myocardium and liver among humans using (123)I-labeled 15-(p-iodophenyl)-3-(R,S)-methyl-pentadecanoic acid ((123)I-BMIPP) and single photon emission computed tomography technique (SPECT). Six untrained male subjects were studied after 35 min of ergometer bicycle exercise at 40, 70 and 80% maximal aerobic power (VO(2max)) One subject was studied as resting control. SPECT scan was done 40 min after (123)I-BMIPP injection. Mean fractional uptake (FU) in quadriceps femoris muscle (QF) were 0.029 +/- 0.001, 0.029 +/- 0.002 and 0.025 +/- 0.002% at 40, 70 and 80% VO(2max), respectively. FU of QF at 40 and 70% VO(2max) were significantly higher than those of 80% VO(2max). Mean FU into myocardium were 0.048 +/- 0.002, 0.052 +/- 0.004 and 0.050 +/- 0.003% and those in liver were 0.033 +/- 0.002, 0.032 +/- 0.002 and 0.034 +/- 0.003% at each loads, respectively. Any significant changes were not suggestive in liver and myocardium after exercise. Mean FU (the mean values of all exercise intensity) at exercise is 2.86, 0.96 and 0.71 times higher than those at rest in QF, myocardium and liver. These results suggest: (1) in skeletal muscles, energy requirements at above lactate threshold at high exercise intensity predominantly depend upon other intramuscular energy substrates, (2) there is possibility of energy compensation by other substrates in myocardium at higher exercise intensity, (3) FFA uptake in liver might decrease after exercise; however, the influence of exercise intensities is not suggested.

Purpose: The dopamine D(2) receptor (D2R) is important in the mediation of addiction. [(123)I]iodobenzamide (IBZM), a SPECT ligand for the D2R, has been used for in vivo studies of D2R availability in humans, monkeys, and rats. Although mouse models are important in the study of addiction, [(123)I]IBZM has not been used in mice SPECT studies. This study evaluates the use of [(123)I]IBZM for measuring D2R availability in mice., Methods: Pharmacokinetics of [(123)I]IBZM in mice were studied with pinhole SPECT imaging after intravenous (i.v.) injection of [(123)I]IBZM (20, 40, and 70 MBq). In addition, the ability to measure the release of endogenous dopamine after amphetamine administration with [(123)I]IBZM SPECT was investigated. Thirdly, i.v. administration, the standard route of administration, and intraperitoneal (i.p.) administration of [(123)I]IBZM were compared., Results: Specific binding of [(123)I]IBZM within the mouse striatum could be clearly visualized with SPECT. Peak specific striatal binding ratios were reached around 90 min post-injection. After amphetamine administration, the specific binding ratios of [(123)I]IBZM decreased significantly (-27.2%; n = 6; p = 0.046). Intravenous administration of [(123)I]IBZM led to significantly higher specific binding than i.p. administration of the same dose. However, we found that i.v. administration of a dose of 70 MBq [(123)I]IBZM might result in acute ethanol intoxication because ethanol is used as a preparative aid for the routine production of [(123)I]IBZM., Conclusions: Imaging of D2R availability and endogenous dopamine release in mice is feasible using [(123)I]IBZM single pinhole SPECT. Using commercially produced [(123)I]IBZM, a dose of 40 MBq injected i.v. can be recommended.

Objective: Earlier studies suggested that elevated cardiac troponin T (cTnT) might be useful for detecting less severe types of myocardial injury (i.e., non-ST segment elevation myocardial infarction). The objective of this study is to elucidate the usefulness of (201)thallous chloride ((201)TlCl) and (123)I-betamethyl-p-iodophenyl-pentadecanoic acid ((123)I-BMIPP) dual-single-photon emission computed tomography (SPECT) imaging for patients with myocardial infarction (MI) without ST segment elevation., Methods: Consecutive 86 patients (56 men and 30 women; mean age 66 +/- 12 years) clinically diagnosed with acute myocardial infarction (AMI) were divided into two groups according to serum creatine kinase MB (CK-MB) and cTnT levels. Group A consisted of 53 patients with increased serum CK-MB and cTnT levels, and Group B, 33 patients with increased serum cTnT without increased serum CK-MB. All patients underwent (201)TlCl and (123)I-BMIPP dual-SPECT about 8 days following the onset. The left ventricular myocardium was divided into 20 segments on each SPECT image, and tracer accumulation in those segments was scored on a five-point scoring system. The total defect scores (TDS) were calculated by summing the scores for all 20 segments, and compared between groups A and B. Group B patients were subdivided into two groups according to the TDS on (123)I-BMIPP images as groups B(S) (severe; TDS > or = 8) and B(M) (mild; TDS < or = 7), and we compared the prognosis over a period of 2 years from the onset between the three groups., Results: The TDS of group A derived from (201)TlCl and (123)I-BMIPP images was significantly higher than those of group B (14.5 +/- 10.8 vs. 1.5 +/- 2.4 and 20.8 +/- 13.3 vs. 9.1 +/- 6.2, respectively; P < 0.0001). The sensitivities of (201)TlCl and (123)I-BMIPP images were 94.3% (50/53) and 96.2% (51/53) to detect the culprit coronary lesions in group A (no significant difference). In contrast, the sensitivity of (123)I-BMIPP images (72.7%, 24/33) was higher than that of (201)TlCl images (27.3%, 9/33) in group B (P < 0.05). At 2 years of follow-up, the incidence of hard cardiac events in groups A, B(S), and B(M) was 24.5%, 27.8%, and 6.7%, respectively. The rate of group BS, as well as that of group A, was significantly higher than that of group B(M) (P < 0.05)., Conclusions: Of those with a clinical diagnosis of AMI accompanied by increased cTnT, the CK-MB negative patients accounted for 38% (33/86) of all patients as having non-ST segment elevation myocardial infarction such as NTMI. For such patients, (123)I-BMIPP imaging is useful not only for the detection of the culprit lesions but also for the prediction of the prognosis.

The authors present a 71-year-old woman who had a right chylothorax after right upper lobectomy for lung cancer. As the chylothorax was considered to be due to thoracic duct injury at the time of operation, lymphoscintigraphy was performed by oral administration of I-123 beta-methyl-iodophenyl pentadecanoic acid (BMIPP). After visualization of the stomach and intestine, abnormal accumulation of the radiotracer was found initially around the right pulmonary hilum and then spread laterally in the upper pleural cavity, indicating chyle leakage in the region of the right pulmonary hilum. Scintigraphic finding was well correlated with the subsequent thoracoscopic observation, showing chyle leakage from a lymphatic tributary near its confluence to the thoracic duct at the level of the azygos continuation. The disruption site was ligated by video-assisted-thoracoscopic-surgery procedure with successful termination of the chyle leakage. Lymphoscintigraphy by oral administration of I-123 BMIPP is thought to be a useful method for localization of chyle leakage in patients with chylothorax induced by thoracic surgery.

Purpose: 123I-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (123I-BMIPP) is a fatty acid analog for single-photon emission computed tomography (SPECT) imaging that is mainly stored in the triglyceride pool. Low-dose dobutamine infusion has been reported to improve BMIPP uptake in the stunned myocardium, but the mechanism underlying this effect remains unclear. The purpose of this study was therefore to investigate the myocardial metabolism of 123I-BMIPP in the stunned myocardium under low-dose dobutamine infusion, and to elucidate the mechanism by which dobutamine improves BMIPP uptake., Methods: Using open-chest dogs, stunned myocardium was induced by occlusion of the left anterior descending artery (LAD) for 30 min, with subsequent reperfusion (ischemia group, n=6). After direct injection of BMIPP into the LAD, myocardial extraction and retention were examined and metabolites evaluated (using high-performance liquid chromatography) during dobutamine infusion. The results in the ischemia group were compared with findings obtained in a control group under dobutamine infusion (n=6)., Results: Dobutamine infusion significantly increased both the rapid extraction (within 30 s) of BMIPP into the myocardium (control vs ischemia group: 48+/-19% vs 66+/-14%, p<0.05) and its subsequent retention (73+/-13% vs 85+/-8%, p<0.05). The metabolites from the myocardium consisted of back diffusion of nonmetabolized BMIPP, the alpha-oxidation metabolite, intermediate metabolites, and the full-oxidation metabolite. Among these metabolites, the full-oxidation metabolite decreased significantly (from 34.0+/-20.0% to 15.8+/-9.3%, p<0.05) in the stunned regions, though back diffusion of nonmetabolized BMIPP increased (from 51.3+/-21.9% to 71.3+/-10.1%, p<0.05)., Conclusion: These results indicate that increased uptake of BMIPP in stunned myocardium is mainly due to decreased beta-oxidation in tissue and increased shunt retention of BMIPP in the triglyceride pool, and thereby provide further insight into the pathophysiology of stunned myocardium.

Purpose: To investigate the use of orally administered iodine-123-labeled 15-(4-iodophenyl)-3(R,S)-methyl-pentadecanoic acid (I-123 BMIPP) for thoracic duct imaging in normal and pathologic states and to study the tracer distribution and dynamics in healthy participants., Methods: The radiotracer was administered with solid (in three healthy persons and one patient) or liquid meals (in three other healthy persons). Solid meals contained relatively more fat content than did the liquid meal. Images were acquired to trace the passage of radiotracer from the intestine to the systemic venous circulation via the lymphatic route. Multiple static planar images were acquired in the anterior and posterior views. Blood samples were analyzed for radioactivity and serum triglyceride levels., Results: In the healthy participants, I-123 BMIPP was absorbed from the intestine and reached the venous circulation through the thoracic duct. The thoracic part of the duct was visualized successfully in all healthy persons within 80 minutes. The radiotracer dynamics varied according to the type of meal administered. The patient had chylomediastinum and right chylothorax and underwent thoracic duct ligation. In the patient, marked stasis in the collateral lymphatic channels was seen, as was chylous leakage into the mediastinal space and right pleural cavity. Passage of tracer to the general venous circulation was delayed. A normal thoracic duct was not seen in this patient., Conclusions: Scintigraphy by orally administered I-123 BMIPP is a simple method to image the thoracic duct and to monitor its lesions. Meals with a higher fat content result in better BMIPP absorption and may be used as a standard method.

Unlabelled: Chylothorax can occur secondary to traumatic lesions of the thoracic duct caused by chest injuries, surgical procedures involving the pleural space, neoplasms or malformations of the lymphatics., Methods: Lymphatic leakage sites were localized by scintigraphy after oral administration of the 123I-labeled long-chain fatty acid derivative iodophenyl pentadecanoic acid (IPPA). We report on three patients with different lymphatic leakage sites and on one normal control subject., Results: IPPA scintigraphy localized the lymphatic leakage site correctly in all three patients. In two of them, the method even guided the successful surgical treatment of the leakage., Conclusion: This approach is suitable for detecting lymphatic leakages of intestinal origin.

Background: Short-gut syndrome is likely to impair enteric fat utilization. This study was undertaken to develop a clinical test of lipid absorption without fecal collection., Methods: The absorption of enterally fed radioactive long-chain fatty acid, beta-methyl-p-(123I)-iodophenylpentadecanoic acid was investigated with continuous chyle collection in rats. The changes in excretion and time-dependent biodistribution of radioactivity of the enterally fed agent were assessed in normal control animals. Similarly, sequential urinary excretion and biodistribution were studied along with scintigraphy using sham-operated and short-gut animals., Results: Approximately 64% of the enterally fed radioactivity was recovered in the collected chyle (24 hours). A comparison of normal control, sham-operated, and short-gut animals showed significantly less urinary and greater fecal excretions of radioactivity in short-gut animals. With the use of sequential scintigraphy, the small intestine, whole-body soft tissues, and urinary bladder were well visualized in sham-operated animals, whereas the large intestine and feces were demonstrated earlier in short-gut animals., Conclusions: Our results suggest that enteral feeding of the agent might be feasible for determining lipid absorption from the the dynamic changes of radioactivity in visualized abdominal organs and in urine.

1. Inhibition of neutral endopeptidase (NEP), the degradative enzyme for atrial natriuretic peptide, was studied in vitro and in vivo using a previously characterized NEP inhibitor radioligand, 125I-labelled RB104. 2. SCH 42354, the active di-acid of the ethylester prodrug, SCH 42495, caused a concentration-dependent displacement of 125I-labelled RB104 from rat renal NEP. The concentration of SCH 42354 that displaced 50% of radioligand bound to the enzyme NEP (IC50) was 3.3 +/- 0.1 nmol/l (mean +/- SEM). Enalaprilat, an angiotensin converting enzyme inhibitor, did not displace 125I-labelled RB104 in concentrations up to 10 mumol/l. 3. In adult normotensive Sprague-Dawley rats, oral SCH 42495 (3-300 mg/kg) caused significant inhibition of renal NEP (P < 0.001). SCH 42495 had no effect on renal or plasma angiotensin converting enzyme activity, but high-dose SCH 42495 (300 mg/kg) caused a significant increase in plasma renin activity (P < 0.01). 4. In a time course study, oral SCH 42495 (30 mg/kg) caused rapid (within 30 min) and significant inhibition of renal NEP for up to 48 h (P < 0.001). No changes in plasma atrial natriuretic peptide or plasma angiotensin converting enzyme activity were seen. 5. These data provide evidence that short-term administration of the NEP inhibitor SCH 42495 results in inhibition of renal NEP and does not inhibit the circulating or the tissue renin-angiotensin system. The NEP inhibitor radioligand 125I-labelled RB104, is a useful tool to study tissue NEP inhibition after administration of NEP inhibitors.

Iodine-131 labelled meta-iodobenzylguanidine ([131I]MIBG) is used for diagnostic scintigraphy and radionuclide therapy of neural crest-derived tumours. After administration of therapeutic doses of [131I]MIBG (3.1-7.5 GBq) to 17 patients (n=32 courses), aged 2-73 years, 56%+/-10%, 73%+/-11%, 80%+/-10% and 83%+/-10% of the dose was cumulatively excreted as total radioactivity in urine at t=24 h, 48 h, 72 h and 96 h, respectively. Except for two adult patients, who showed excretion of 14%-18% of [131I]meta-iodohippuric acid ([131I]MIHA), the cumulatively excreted radioactivity consisted of >85% [131I]MIBG, with 6% of the dose excreted as free [131I]iodide, 4% as [131I]MIHA and 2.5% as an unknown iodine-131 labelled metabolite. Cumulative renal excretion rates of total radioactivity and of [131I]MIBG appeared to be higher in neuroblastoma and phaeochromocytoma patients than in carcinoid patients. Based on the excretion of small amounts of [131I]meta-iodobenzoic acid in two patients, a possible metabolic pathway for [131I]MIBG is suggested. The degree of metabolism was not related to the extent of liver uptake of radioactivity.

Neuroblastoma (NB), a childhood radiosensitive tumor, is very aggressive and malignant, in its disseminated form, despite very intensive chemotherapy, prognosis continues to be dismal. Owing to its capacity to concentrate in NB lesions, large doses of 131-I-MIBG, have given very encouraging therapeutic results in patients resistant to conventional therapy as well as at diagnosis. We recently reported the first attempt in combination therapy (CO-TH) using 131-I-MIBG and cisplatin. This new form of CO-TH appears very effective in obtaining a rapid and excellent response in relapsed patients. In this report, we describe the results of further experience with CO-TH in disseminated NB. We have attempted to verify to what extent interaction between the effects of the two agents may produce therapeutic benefit, and we have sought the optimization of CO-TH use. Three stage IV NB patients were treated with CO-TH. The following treatment schedule, was planned: day 1, cisplatin 50 mg/m3 i.v. over 6 h; day 2, 131-I-MIBG 100-130 mCi at high specific activity (-1.1 Gbq/mg) i.v. over 6 h followed, a week later, by the same treatment combination. The therapeutic results were encouraging. However, hematological toxicity continued to represent a major limiting factor. In view of the overall effectiveness of CO-TH, at the price of lasting hematological toxicity, it may be indicated as a consolidation regimen some time before conditioning chemotherapy for autologous bone marrow transplantation.

During the last two decades, there has been a trend to use low-dose I-131 ablation therapy in patients with thyroid carcinoma without metastases. However, information regarding the incidence of acute adverse reactions in patients after low-dose radioiodine therapy has not been reported. In this study, the acute radiation effects after low-dose radioiodine ablation therapy in postsurgical differentiated thyroid cancer patients was evaluated. Fifty-six patients with differentiated thyroid cancer were prospectively evaluated. None of these patients had evidence of a distant metastasis. All patients received 40 mCi (1480 MBq) I-131 MIBG orally and were evaluated for symptoms and signs by a physician on the second and seventh days after therapy. Xerostomia and nausea were the most common complaints with the same incidence rate of 5.35%. Gastralgia occurred at a frequency of 3.57%. Pain in the thyroid bed, tenderness over a parotid gland, submandibular glands, change in taste, and vomiting all were found at a frequency of 1.78%. Maximum reactions generally occurred 24-48 hours after therapy. All the symptoms except for xerostomia resolved completely in most patients within a week. In comparison with high-dose ablation therapy published in the literature, the incidence of radiation reactions in low-dose radioiodine therapy was much lower. It was concluded that in patients without lymph node or distant metastases, low-dose I-131 MIBG therapy may be recommended to avoid the high incidence of local complications after high-dose treatment.

Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study. We tested the utility of (+)-m-[125I]iodobenzyl)trozamicol(+)-[125I]MIBT), a novel radioligand that binds to the vesamicol receptor located on the synaptic vesicle in presynaptic cholinergic neurons, as a functional marker of cholinergic activity in the conduction system. The (+)-[125I]MIBT was injected intravenously into four rats. Three hours later, the rats were killed and their hearts were frozen. Quantitative autoradiography was performed on 20-micron-thick sections that were subsequently stained for acetylcholinesterase to identify specific conduction-system elements. Marked similarities existed between (+)-[125I]MIBT uptake and acetylcholinesterase-positive regions. Optical densitometric analysis of regional (+)-[125I]MIBT uptake revealed significantly greater (+)-[125I]MIBT binding (nCi/mg) in the atrioventricular node (AVN) and His bundle regions compared with other conduction and contractile elements (AVN: 3.43 +/- 0.37; His bundle: 2.16 +/- 0.30; right bundle branch: 0.95 +/- 0.13; right atrium: 0.68 +/- 0.05; right ventricle: 0.57 +/- 0.03; and left ventricle: 0.57 +/- 0.03; p < 0.05 comparing conduction elements with ventricular muscle). This study demonstrates that (+)-[125I]MIBT binds avidly to cholinergic nerve tissue innervating specific conduction-system elements. Thus, (+)-[125I]MIBT may be a useful functional marker in studies on cholinergic innervation in the cardiac conduction system.

Aim: The determination of the amount of free [131I]iodide in [131I]metaiodobenzylguanidine ([131I]MIBG) concentrates for intravenous infusion under different storage conditions derived from daily practice., Method: The percentage of free [131I]iodide was determined in [131I]MIBG concentrates (1.6-3.9 GBq in 7.5 ml), kept on dry ice (up to expiry, 3 days after production) or, after thawing, at room temperature (up to 24 h). A validated solid phase extraction (SPE) assay was used., Results: Free [131I]iodide increased from 1.9% +/- 0.34% at production to 4.4% +/- 0.67% (mean +/- SD; n = 5) at expiry in 3.7 GBq per 7.5 ml [131I]MIBG infusion concentrates stored on dry ice (-78 degrees C). At room temperature, formation of free [131I]iodide was found to be dependent on the radioactive concentration of the fluid. [131I]iodide levels increased from 3.1%, immediately after thawing, to 6.6% and 16.6% at t = 5 and 24 h, respectively, for a 3.9 GBq per 7.5 ml concentrate., Conclusion: The investigated formulation of [131I]MIBG concentrates, stored in its original packing containing dry ice, can generally be used up to expiry. After thawing, the undiluted concentrates should be administered to a patient within 3.5 h.

Unlabelled: In the treatment of neural crest tumors, such as pheochromocytoma, with[131I]MIBG, bone marrow toxicity limits the amount of administered activity and, thus, a therapeutically useful tumor dose., Methods: We calculated tumor doses in a series of diagnostic studies with [123I]MIBG using accurate quantification of SPECT and planar scintigraphy. By extrapolating diagnostic results to therapeutic activities of [131I]MIBG, we could compare the results with whole-body doses from a series of therapies., Results: The tumor dose was DT = 2.2 mGy MBq(-1) (median value of 27 measurements, range 0.04 < or = DT < or = 20 mGy MBq(-1) and the whole-body dose in a series of 16 patients undergoing 50 therapies was DWB = 0.12 +/- 0.04 mGy MBq(-1) (mean +/- s.d.). The therapeutic ratio varied between 130 to below 10 in some patients., Conclusion: The results were compared with published data. We found clearly skewed distribution of tumor doses, with a majority of tumors receiving only a few mGy per MBq administered activity. In some patients, however, doses did reach 20 mGy MBq(-1).

Recurrent or persistent neuroblastoma in stages III and IV is usually fatal despite modern therapies. Metaiodobenzylguanidine labeled with 131-I (131-I MIBG) concentrates in most neuroblastoma and when given in doses that impart therapeutic radiation, has produced remissions in patients with these tumors. However, success with 131-I MIBG has been limited. The physical characteristics of radiation imparted by 125-I MIBG theoretically could overcome some of the limitations that restrain the therapeutic effects of 131-I MIBG in patients with neuroblastoma. Thereby, 125-I MIBG may offer advantages over 131-I MIBG in the treatment of neuroblastoma. Ten children who manifested persistent/recurrent stage III or IV neuroblastoma were given 8.3 to 30.1 GBq or 224 to 814 mCi of 125-I MIBG in a phase I-II trial. Five of the patients had progression-free survivals > 1 year (continuing in three patients), and four of these subjects are surviving 17 to 52 months after treatment with 125-I MIBG. With appropriate doses of 125-I MIBG, life-threatening toxicity can be avoided. Thus, survivals after 125-I MIBG appear to be as long or longer than those historically observed following other treatments for patients similarly afflicted with refractory neuroblastoma.

The potential role [131I]MIBG therapy in untreated, inoperable cases of neuroblastoma (NB) in children was evaluated. Six children, aged 10 months-5 years, were treated at diagnosis. Five (4 stage III and 1 stage IV NB) underwent [131I]MIBG treatment alone (single doses ranging from 2.9 to 6.1 GBq of high specific activity [131I]MIBG. In one case (stage IV NB) [131I]MIBG was preceded by Cisplatin administration (20 mg/m2/day) given over a 5 day period. The results obtained in the first 5 cases were as follows: 1 complete response still lasting after 5 years; 1 partial and 1 minor response allowing further surgery and chemotherapy; 2 stabilization of the disease. The treatment was well tolerated with minimal toxicity. However, apart from the first case all these children relapsed and subsequently died. Therefore [131I]MIBG therapy (9.1 GBq given in 2 courses) combined with Cisplatin as a "radiosensitizer" was used in the sixth case, a patient with widespread bone metastases and massive bone marrow involvement. A very good partial response was obtained in this case. Further surgery (of the primary NB) and multidrug chemotherapy was then possible. In conclusion, [131I]MIBG therapy at diagnosis appears to be effective, low toxic treatment of NB; when integrated with Cisplatin its efficacy seems to improve even more.

Chemodectoma is a rare, slow growing neoplasm with local aggressiveness and a high rate of residuals after surgery, arising from paraganglionic tissue (neural crest) and therefore able to take up Metaiodobenzylguanidine (MIBG). The aim of this study was to evaluate the diagnostic accuracy of 123I-MIBG Single Photon Emission Computed Tomography (SPECT) in comparison to Selective Digital Angiography (SDA), Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). We studied 50 patients (41 women, 9 men) mean age 56 years (range 14-79), with diagnostic suspicion of chemodectoma (CH). There were 2 groups of patients: Group A (26 patients) examined before Surgery and Group B (24 patients) examined after surgery. SPECT of the head and neck region was performed 4 hours after i.v. administration of 185 MBq of 123I-MIBG. All patients were pre-treated with iodine solution. We performed a qualitative evaluation of the reconstructed slices. In Group A, all patients with CH (24) showed accumulation of MIBG in agreement with SDA, CT and MRI: 2 patients (histologically one had a cordoma, the other metastasis of papillary thyroid carcinoma), did not show any accumulation of 123I-MIBG. In Group B, 6 patients showed accumulation of 123I-MIBG in local residuals, and 9 were negative. Six patients with a lesion smaller than 1.5 cm were negative. Three patients had a positive scan but no lesion on SDA, CT and MRI. 123I-MIBG SPECT proved to be useful procedure in the diagnosis of untreated CH. During follow-up after surgery this procedure may assume a role in the perspective of radiometabolic therapy with 131I-MIBG.

The international workshop on metaiodobenzylguanidine (MIBG) and radiolabeled somatostatin analogs held in Rome in June, 1994 addressed a wide range of topics which might be classified into five broad general themes: Theme 1. The role of MIBG for the location of neuroendocrine tumors. A) The range of tumors in which MIBG scintigraphy is effective (pheochromocytomas, neuroblastoma, chemodectoma and other APUDomas). B) The increasing popularity of 123I as a radiolabel for MIBG (potential advantages in planar and SPECT imaging). C) MIBG as the prototype of a family of radiopharmaceuticals exploiting the biogenic amine uptake and storage mechanisms. (Other radiohalides 124I, 125I, 87Br, 211At, 18F; other PET radiopharmaceuticals such as 11C-epinephrine, 11C-hydroxyephedrine). Theme 2. The role of MIBG as an in vivo scintigraphic probe of the sympathetic nervous system. A) Cardiac sympathetic innervation (in cardiomyopathy, myocardial infarction, and as a prognostic index for cardiac transplantation). B) Pulmonary MIBG uptake as index of pulmonary endothelial/sympathetic function (MIBG by both the intravenous and inhaled routes of administration). Theme 3. MIBG for the radiopharmaceutical therapy of neuroendocrine tumors. A) Treatment of neuroblastoma early in the natural history of the disease (MIBG therapy as initial management, MIBG therapy combined with other modalities--e.g., chemotherapy and bone marrow transplantation). Theme 4. The role of radiolabeled somatostatin analogs for the location of neuroendocrine and other tumors. A) The range of tumors in which somatostatin receptor radiopharmaceutical scintigraphy is effective (pituitary tumors, central nervous system tumors, carcinoids, islet cell tumors, medullary thyroid carcinoma, small cell lung cancer, APUDomas). B) The superiority of 111In over 123I as a radiolabel (the future of potential 99mTc and other labels). C) Somatostatin receptor scintigraphy in autoimmune and other disorders. D) Pentetreotide as the prototype of a wide range of radiolabeled peptides as radiopharmaceuticals for the in vivo depiction of the receptors for peptide hormones, lymphokines, paracrine and other information transmitting molecules (the general concepts include the use of long-acting, slowly degraded analogs and the development of generally applicable labeling techniques. Examples include 123I-ANF, labeled interleukins and other lymphokines). Theme 5. Comparisons of MIBG and pentetreotide scintigraphy for the location of neuroendocrine tumors. A) The range of neuroendocrine and other tumors (e.g., pheochromocytomas, neuroblastomas, carcinoids, islet cell tumors and other APUDomas).

The observed response to [131I]MIBG therapy in advanced neuroblastoma after conventional therapy, the noninvasiveness of the procedure, and the high metabolic activity which is frequently observed in untreated tumors led to the concept of substituting [131I]MIBG therapy for combination chemotherapy at diagnosis prior to surgery in patients with advanced disease/high risk neuroblastoma. The objective of this approach is to reduce the tumor volume, enabling adequate surgical resection of the tumor, and to avoid toxicity and the induction of early drug resistance. Chemotherapy is reserved to treat minimal residual disease postoperatively. Thirty-one children who presented with inoperable neuroblastoma were treated according to this protocol. After an objective response to [131I]MIBG therapy at diagnosis, 19 of 27 evaluable patients (70%) had complete or > 95% resection of the primary tumor or did not require surgery at all. Only mild hematological toxicity was observed. It is concluded that [131I]MIBG therapy of neuroblastoma at diagnosis is feasible; its effectiveness in attaining operability of the primary tumor is at least equal to that of combination chemotherapy, but its toxicity is considerably less.

The avidity of many metastatic pheochromocytomas and neuroblastomas for metaiodobenzylguanidine (MIBG) observed at diagnostic scintigraphy has led to attempts to treat these lesions with large doses of MIBG. We and others have achieved therapeutic responses with 131I-MIBG (usually partial) in about a third of malignant pheochromocytomas. A small but important subgroup of advanced, poor prognosis neuroblastomas which have been resistant to all other therapies have also shown responses including occasional long-term survival (> 5 years) and apparent complete responses to 131I-MIBG. Because the physical properties of 131I are suboptimal for the delivery of therapeutic radiation to bone marrow micrometastases, a frequent problem in neuroblastoma, we have performed preliminary studies in poor prognosis Stage III and VI neuroblastoma using 125I-MIBG which has more satisfactory emissions. This has led to prolonged tumor stabilization and survival (> 19 to > 52 months) in 5 of 10 patients. MIBG radiopharmaceutical treatment of neuroendocrine tumor patients must still be considered an experimental but nevertheless promising treatment modality.

Metastatic neuroblastoma (NB) continues to have a dismal prognosis. NB is a radiosensitive tumor. Owing to its high concentration in the NB lesions, Metaiodobenzylguanidine (MIBG) has the potential for specifically delivering very large radiation doses to the malignant cells. Encouraging results have been reported with [131I]MIBG used alone in patients resistant to conventional therapy and at diagnosis. We report the first attempts to explore the integration of this new treatment modality with chemotherapy. Among the drugs effective in NB, cisplatin was chosen because of its high degree of activity against NB, its mild hematologic toxicity and the known synergism between cisplatin and radiation. Four patients, 3 with relapsed, heavily pre-treated, progressive stage IV NB, and 1 with stage IV NB at diagnosis, all with a good [131I]MIBG uptake, were investigated with the combined therapy. Two complete remissions and one partial remission were observed in the relapsed patients 4-6 weeks following only one single course of both cisplatin and [131I]MIBG at the "standard" dosage. The only toxicity was hematologic, which was significant and relatively long-lasting, but was not associated with any serious infections or bleeding tendency. The general condition of these patients during the entire study period was excellent. The 4th patient, investigated at diagnosis with a modified less intensive treatment, obtained a partial remission with a mild hematologic toxicity. The provisional conclusion of this preliminary study is that this new form of combined therapy appears very effective in heavily pretreated relapsed patients with progressive disease, and could also be investigated in refractory patients and in patients at diagnosis.

Norepinephrine (NE) is one of the many biologically active substances that are metabolized by the lung. The norepinephrine uptake in the lung has been widely investigated in animal studies in order to detect abnormalities of the endothelial cells. 131I- or 123I-labelled metaiodobenzylguanidine (MIBG) is a radioactive tracer that shares several metabolic pathways with NE; it has been used instead NE or both in animal and in human studies for the same purposes. It has been definitely demonstrated that MIBG lung uptake following intravenous administration is a reliable marker of minimal endothelial cell lesions and it allows one to investigate several conditions involving damage to the lung vasculature such as adult respiratory distress syndrome, post-actinic lung fibrosis or chemotherapic lung toxicity. MIBG could also potentially be used as a tracer of the neuroadrenergic system of the airways, once it has been deposited in the whole branches of the bronchial tree. With this in mind we evaluated the feasibility of the administration of MIBG in radioaerosol form. We first performed a chromatographic study on [123I]MIBG aliquots aerosolized for variable lengths of time (2-30 minutes). Radiochemical purity was always over 96%, thus demonstrating that aerosolization does not significantly modify the stability of the tracer. We then compared both the lung clearance curves and the scintigraphic images in two groups of normal subjects who respectively underwent [123I]MIBG and 99mTc-DTPA radioaerosol dynamic scintigraphy. We found that MIBG clearance to be significantly lower than that of DTPA (135 +/- 32 minutes versus 69 +/- 27 minutes, p < 0.01), probably due to its being trapped in the adrenergic nerve endings of the airways. The pulmonary distribution of both tracers was homogeneous, as demonstrated by the correspondence of the values for the aerosol penetration index in both groups of subjects. Such results warrant further research and pharmacologic tests.

The aim of the present study was to assess the utility of SPECT imaging with [123I]MIBG in patients with neuroblastoma (NB). Twenty-two children were studied (11 males and 11 females: age range: newborn to 11 years). A total of 39 studies were performed in different clinical phases. Both planar (at 24 and occasionally 48 hours) and SPECT (at 24 hours) imaging were performed in all cases. Planar studies gave a sensitivity of 87.5% (evidence of the disease in 21 of 24 studies performed in children with known NB lesions) and a specificity of 93.3% (true negative results in 14 of 15 studies performed in disease-free patients). In the same patients SPECT gave a sensitivity of 95.8% (23 of 24 positive studies and a specificity equal to that of planar scanning. In 5 of 21 studies positive at planar scanning SPECT showed 9 additional lesions. In conclusion, [123I]MIBG SPECT imaging compared to planar scanning can demonstrate a greater number of lesions. Its use seems to be indicated mainly in cases in which diagnostic assessment is difficult, such as small residual tumors or in the follow up of children no longer in therapy, in whom it can lead to an early diagnosis of relapse.

For more than a decade radioiodinated metaiodobenzylguanidine (mIBG) has been commonly used for neuroblastoma imaging. The accuracy of this scintigraphic method in detecting both primary and secondary tumour sites is crucial when evaluating the extent of disease. The aim of our study was to assess the impact of high-activity mIBG scintigraphy on neuroblastoma staging. Eighteen scans (TS) were obtained in 15 children after a therapeutic dose of iodine-131 mIBG and compared to diagnostic mIBG scans (DS) (in eight cases with 131I-mIBG and in ten cases with 123I-mIBG). The superiority of TS over DS was confirmed by the overall results: a total of 220 lesions were disclosed with TS and 171 with DS. However, in only one case did the TS findings, namely skeletal involvement not evidenced on corresponding DS, have an impact on clinical staging. In contrast, neither TS nor DS detected proven bone involvement in four patients. The dose-related sensitivity of mIBG scintigraphy in detecting neuroblastoma tumour sites was confirmed. The ultimate impact of high-dose scans on neuroblastoma management, however, seems limited.

Dosimetric calculations have been made for organ doses in patients receiving 131I-MIBG therapy as treatment for neuroblastoma. As well as whole body and liver dose, consideration has been given to dosimetry of organs (lung, urinary bladder) whose tolerance may become treatment limiting when 131I-MIBG is given as part of combined modality therapy. Data from both adults and children receiving radiolabelled MIBG for diagnostic or therapeutic purposes have been compared in constructing dosimetry models for children. A recently published urodynamic model has been used in the estimation of radiation dose to the bladder. The results show that liver and lung may receive doses greater than the average total body dose (0.58 mGy MBq-1 and 0.35 mGy MBq-1, respectively, as compared with 0.25 mGy MBq-1 to the whole body). The organ dose estimates do not differ greatly from previous analyses except in the case of the bladder for which the new modelling studies have resulted in lower dose estimates (0.76 mGy MBq-1 administered, for dose to bladder surface from bladder contents) than in some published series. This may result from differing assumptions regarding parameters such as bladder content and urine flow rate, an enhanced fluid intake being assumed in the present bladder dose estimates. Average doses to the bladder wall from the contents were estimated to be 7.4-11.3% of the surface doses. The urodynamic modelling analysis shows that the bladder could receive a much greater dose (by an order of magnitude) in patients who were inadequately hydrated or had impaired renal function.

The purpose of this study is to clarify whether dynamic SPECT (DECT) immediately after the injection of 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) may represent myocardial perfusion imaging. Ten patients with unstable angina pectoris (UAP), 11 patients with acute myocardial infarction (AMI) and 6 patients with non-ischemic heart disease (NIHD) were studied using BMIPP myocardial scintigraphy with DECT. DECT acquisition was started 2 minutes after the injection of BMIPP, and DECT images were obtained every three minute for 15 minutes with 3-headed gamma camera SPECT system. Additionally, static SPECT images were acquired 30 minutes after the injection of BMIPP. These SPECT images of BMIPP were compared with thallium-201 myocardial perfusion images at rest. In UAP group, early DECT images showed almost the same findings as thallium-201 images in 8 of 10 patients, and SPECT images at 30 minutes after the injection showed reduced accumulation of BMIPP compared with thallium-201 images in all patients. In AMI group, early DECT images showed the same findings as thallium-201 perfusion images in 9 of 11 patients, and SPECT images at 30 minutes after the injection showed reduced accumulation of BMIPP compared with thallium-201 images in 5 of 11 patients. These results indicate that myocardial perfusion can be evaluated in the early image using DECT, in addition to myocardial fatty acid metabolism in the delayed image.

Three patients with malignant pheochromocytoma were treated with intravenous infusion of 131I-MIBG. The dose per therapy ranged from 2.33 to 4.03 GBq. The repeated therapies were performed at intervals of 6, 11, 10 and 13 months in the first patient, 17 and 11 months in the second patient and 9 months in the third patient. Lumbago disappeared but little objective improvement was achieved in the first patient. The second patient exhibited a gradual decrease in catecholamine values with no change in tumor size. Remarkable decreases in tumor size and catecholamine values were observed in the third patient. No side effect was observed in any patient. The radiation dose absorbed by the main tumor was the highest at the first therapy and decreased with the number of therapies: 42, 26, 19, x and 9.0 Gy in the first patient, 63, 20 and 8.8 Gy in the second patient, and 81 and 40 Gy in the third patient. This was due mainly to the decrease in % uptake by the tumor of the 131I-MIBG dose administered. Therefore the increase in the dose of 131I-MIBG administered at the first therapy and/or shorter interval therapies seems to be important to obtain more therapeutic effects on malignant pheochromocytoma.

A 39-year-old woman with Sipple's syndrome and a malignant pheochromocytoma (PHE) is presented. She is a member of a big family with this syndrome and had undergone bilateral, subtotal adrenalectomy because of bilateral PHE six years prior to the present admission. In 1989, a small nodule was identified in her right thyroid lobe by ultrasonography and was suspected to be a medullary thyroid carcinoma (MTC). Further examinations revealed the coexistence of multiple lung and liver masses. These tumors were considered to be metastases of PHE because of the increased urinary excretion of catecholamines as well as extremely high catecholamines both in the hepatic venous blood and in the cystic fluid of the liver tumor even though there was no apparent recurrences of PHE in the adrenal region. After surgical removal of the MTC in August, 1989, she was given 3.7 GBq of 131I-metaiodobenzyl guanidine (131I-MIBG) infusions twice--in October, 1989 and in August, 1990. 131I-MIBG showed a strong accumulation in the lung and liver masses on both occasions. Periodic increases in blood pressure and tachycardia with an excessive catecholamine secretion were observed over two weeks after the first treatment. However, this treatment was not effective in reducing urinary catecholamines nor the size of the metastatic tumors. She, therefore, underwent chemotherapy with cyclophosphamide, vincristine and decarbazine in 1991, which slightly but significantly reduced urinary excretion of catecholamines and the size of the lung tumors. She had clinically stable period for one year after the treatment but rapid growth of these metastatic tumors occurred afterwards and she died in August, 1992.(ABSTRACT TRUNCATED AT 250 WORDS)

Since radiographic findings on oral cholecystography (OCG) have implications for the eligibility for nonsurgical therapy of elderly patients, we investigated the OCGs of 448 symptomatic gallstone patients (109 male, 339 female; mean age, 49.8 +/- 14 (range, 21-88)). Opacification of the gallbladder was found in 323 cases (72.1%). Calcifications of gallstones were found in 85 opacified gallbladders (26.3%). Solitary and multiple stones were calcified in 35.3% and 18.2%, respectively (P < 0.0005). When divided into two groups (< or = 40 years and > 40 years), there was a significant increase in calcifications (P < 0.02) and a non-significant increase in opacification with increasing age. It is concluded that age is a determinant for calcification of gallstones and not opacification of the gallbladder. Since multiple stones are proportionately observed more in clinical studies than in epidemiologic studies, it is suggested that multiplicity of stones predisposes to biliary complaints. That solitary stones are more likely to be calcified than multiple stones, adds to the hypothesis that solitary and multiple stones have a different pathogenesis. Elderly patients, in whom non-surgical therapy is most likely to be indicated and cost-effective, are less likely to be suitable for this form of treatment, since age is a determinant for stone calcification.

We searched for methods that would enable prescriptions of the maximum tolerable doses of iodine-131 metaiodobenzylguanidine (MIBG) and iodine-125 MIBG in the treatment of patients with neuroblastoma. We correlated doses, defined in different ways, with subsequent platelet levels in treated patients to determine accurate predictors of the most frequent toxicity, thrombocytopenia. Nine patients with neuroblastoma were given 131I-MIBG (4.9-8.1 GBq or 132-220 mCi) and ten were given 125I-MIBG (8.3-30.0 GBq or 224-809 mCi) as initial treatments. These therapies were sufficiently varied that correlations could be made between indices of the doses and the subsequent toxicity as reflected in circulating platelet levels. Predictors of toxicity were: whole-body absorbed dose of radiation (cGy) calculated from pretherapy tracer doses of 131I-MIBG; GBq/kg of body weight; and GBq/m2 of body surface area. Toxicity was recorded as the nadir of the platelet level and platelet/pretherapeutic level (platelet ratio). For treatments with 131I-MIBG, the highest correlation was obtained between cGy and the log10-transformed platelet ratio (r = -0.86), but comparison of GBq/m2 and the platelet nadir (r = -0.76) or the platelet ratio (r = -0.74) or the log10 transformed platelet ratio (r = -0.73) gave comparable and statistically significant results. For treatments with 125I-MIBG, significant correlations were obtained between GBq/m2 and the platelet ratio (r = -0.81) or GBq/kg and the log10-transformed platelet ratio; the correlation between cGy and any toxicity index was low. Per administered GBq, 131I-MIBG was 2.6 times more potent than 125I-MIBG in causing a platelet ratio of 0.1.(ABSTRACT TRUNCATED AT 250 WORDS)

131I-labelled metaiodobenzylguanidine ([131I]MIBG) is used both for diagnostic scintigraphy and for radionuclide therapy of neural crest derived tumours in particular neuroblastoma, malignant phaeochromocytoma and paraganglioma. This paper presents data on radiochemical stability during the infusion of 3.8, 5.7 and 7.7 GBq [131I]MIBG in 100 ml infusion fluids for therapy. The period of investigation started at the moment of dilution of the thawed infusion concentrates (t = 0), which arrived in a frozen condition from the manufacturer, and ended at the termination of infusion (t = 7 h). In 7 h the percentage of free [131I]iodide increased from 3.74 to 5.82, from 3.52 to 6.02 and from 3.72 to 6.40% in the 3.8, 5.7 and 7.7 GBq [131I]MIBG infusion fluids, respectively. The 0-7 h increases of the different radioactive concentrations did not differ significantly. All the infusion fluids contained less than 7% free [131I]iodide at the end of infusion (t = 7 h).

Iodine-131 labelled metaiodobenzylguanidine ([131I]MIBG) has a diagnostic and therapeutic role in the management of neural crest tumours, particularly neuroblastoma, malignant phaeochromocytoma and paraganglioma. With therapeutic amounts of [131I]MIBG it is essential that the amount of free [131I]iodide, the most important impurity, is known. In clinical practice the percentage of free [131I]iodide seen in a [131I]MIBG infusion concentrate increased from 2.2% +/- 0.67% to 3.6% +/- 0.39% (mean +/- SD; n = 23) 1 day after production. At the time of use the percentage of free [131I]iodide was always below our upper limit of acceptance of 5%. Since 5% of free [131I]iodide is within practical reach in our environment, a higher percentage at the time of preadministration quality control is not accepted in the Netherlands Cancer Institute.

The use of inteferon (IFN) in neuroendocrine advanced tumors has achieved control of hormonal symptoms but low objective tumor response rate. In patients resistant to, or failing on, IFN a second line treatment may be required. Seventeen patients having received recombinant IFN alpha-2a as last treatment entered the study. There were 12 carcinoids, 3 medullary thyroid carcinomas, one Merkel cell carcinoma, and one neuroendocrine pancreatic tumor. Two different treatments were used: one radiometabolic therapy with metaiodobenzylguanidine (MIBG) in 3 patients with high MIGB uptake and one polychemotherapy regimen, including streptozotocin 500 mg/m2 intravenously days 1, 2, 3 and epirubicin 75 mg/m2 intravenously day 1, in the remaining 14 patients. Stable disease with relief of symptoms and tumor marker reduction was obtained in two patients receiving MIGB therapy, whereas the third patient had progressive disease. In the chemotherapy group only one partial response was obtained and neither tumor marker reduction nor subjective improvement were seen. Our second-line treatment was not especially effective but may be considered for rapidly progressive and/or symptomatic disease. The radiometabolic therapy appears promising in symptomatic patients with small tumor burden whereas our chemotherapy regimen appears ineffective.

In this work, spermhead survival in mouse testis was used to investigate the radiotoxicity of several intratesticularly localized radioiodinated pharmaceuticals. Radioiodines that decay by electron capture and/or internal conversion (123I, 125I) as well as by beta- decay (131I) were coupled to pharmaceuticals that selectively localize in different cell compartments. Dose response curves yield D37 values of 62 cGy, 75 cGy, 61 cGy and 7.7 cGy for 123IMP (N-isopropyl-p-iodoamphetamine), 131IdU (iododeoxyuridine), H131IPDM (N,N,N'-trimethyl-N'-(2-hydroxyl-3-methyl-5-iodobenzyl)-1,3-propanediami ne) and 125IdC (iododeoxycytidine), respectively. At 37% survival, the relative biological effectiveness (RBE) of these radiochemicals, when compared to the pure gamma-emitting radiochemical 7Be-chloride (D37 = 65 cGy), are 1.0, 0.89, 1.1 and 8.4, respectively. Intratesticular 7Be, with an effective half-life of 430 hr in the organ, was used as the source of reference radiation to determine the RBE values because it solely emits 477 keV gamma rays, and the dose to the testis is delivered chronically, as in the case of the other radiocompounds. Subcellular distribution studies show that all of the cellular activity is localized in the cytoplasm in the cases of 123IMP and H131IPDM, while virtually all of 131IdU and 125IdC were bound to DNA in the cell nucleus. In agreement with our earlier in vivo studies, these data show that subcellular distribution plays a key role in the radiotoxicity of Auger electron emitters such as 123I and 125I, and has no role for beta emitters such as 131I. These findings may have implications in the design of radiopharmaceuticals for both diagnosis (localize Auger emitter in cytoplasm of cell) and therapy (localize Auger emitter in cell nucleus).

The association between clinical autonomic dysfunction and myocardial MIBG accumulation was investigated. The study groups comprised 6 male diabetic patients with autonomic neuropathy (ANP+ group), 6 male diabetic patients without autonomic neuropathy (ANP-group), and 6 male nondiabetic control subjects. The mean age was comparable in all groups, and the subjects had no evidence of coronary heart disease. Reduced heart-rate variation in a deep-breathing test was used as a criterion for autonomic neuropathy. Immediately after injection, the peak net influx rate of MIBG to myocardium was significantly (P less than 0.05) reduced in both diabetic groups. At 6 hr after MIBG injection, the MIBG uptake of the myocardium was significantly (P less than 0.05) smaller in the ANP+ group than in the control group. In the ANP- group, the MIBG uptake of the myocardium was between that of the ANP+ group and that of the control group. Our data show that reduced myocardial MIBG accumulation is associated with autonomic dysfunction in diabetic patients, but it can occur to a lesser extent also in diabetic patients without apparent autonomic neuropathy. The measurement of the myocardial MIBG accumulation is a promising new method to detect cardiac sympathetic nervous dysfunction in diabetic patients.