A Phase 1, Multi-Center, Open-Label, Dose-Escalation Study of 131I-CLR1404 in Subjects with Relapsed or Refractory Advanced Solid Malignancies.

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.

Diagnosis and Detection of Myocardial Injury in Active Cardiac Sarcoidosis--Significance of Myocardial Fatty Acid Metabolism and Myocardial Perfusion Mismatch.

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.

Serial changes in glucose-loaded 18F-fluoro-2-deoxyglucose positron emission tomography, 99mTc-tetrofosmin and 123I-beta-methyl-p-iodophenyl-penta-decanoic acid myocardial single-photon emission computed tomography images in patients with anterior acute myocardial infarction.

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-ß-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.

Prognostic value of (123)I-betamethyl-p-iodophenyl-pentadecanoic acid single-photon emission computed tomography in diabetic patients with suspected ischemic heart disease.

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.

Treatment of a malignant pheochromocytoma in a dog using 131I metaiodobenzylguanidine.

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.

The impact of the excimer laser on myocardial salvage in ST-elevation acute myocardial infarction via nuclear scintigraphy.

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 = (∑123I-BMIPP defect score at 3-7 days after p-PCI - ∑99mTc-tetrofosmin defect score at 3-6 months after p-PCI)/∑123I-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.

Pretreatment CLR 124 Positron Emission Tomography Accurately Predicts CLR 131 Three-Dimensional Dosimetry in a Triple-Negative Breast Cancer Patient.

INTRODUCTION: CLR1404 is a theranostic molecular agent that can be radiolabeled with 124I (CLR 124) for positron emission tomography (PET) imaging, or 131I (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, R2 ≥ 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.

A low perfusion-metabolic mismatch in 99m Tl and 123 I-BMIPP scintigraphy predicts poor prognosis in systemic sclerosis patients with asymptomatic cardiac involvement.

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-ß-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.

Usefulness of 201TlCl/ 123I-BMIPP dual-myocardial SPECT for patients with non-ST segment elevation myocardial infarction.

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.

Noninvasive detection of cardiac sympathetic nervous dysfunction in diabetic patients using [123I]metaiodobenzylguanidine.

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.

Localization of chyle leakage site in postoperative chylothorax by oral administration of I-123 BMIPP.

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.

Dual pancreas- and lung-targeting therapy for local and systemic complications of acute pancreatitis mediated by a phenolic propanediamine moiety.

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.

Use of m-[131I]iodobenzylguanidine in the treatment of malignant pheochromocytoma.

The efficacy and safety of m-[131I]iodobenzylguanidine ([131I]MIBG) were assessed in 15 patients with malignant pheochromocytomas in a nonrandomized, single arm trial, in which patients were treated with [131I]MIBG (SA, 740 megabequerel/mg) every 3 months. Seven of these patients had bone and soft tissue metastases, 4 had only soft metastases, and 4 had only bone metastases. The follow-up period ranged from 6-54 months; the number of doses ranged from 2-11, with 2.9 (78.4 mCi) to 9.25 gigabequerel (GBq) (250 mCi)/administration and a cumulative activity from 11.1-85.90 GBq (300-2322 mCi). The absorbed cumulative dose in tumors ranged from 12-155 Gy. A beneficial effect of the treatment was observed in 9 patients (60%). No complete remission of the disease was observed. Seven patients died during the study, among whom 4 never responded to the treatment. Seven had hormonal responses (4 complete and 3 partial), with a duration ranging from 5-48 months. Among these patients, 4 relapsed, and 3 died within 3 months. Five patients had partial tumoral responses mainly located in soft tissues and for a duration ranging from 29-54 months. All patients with a hormonal response had objective improvement in clinical status and blood pressure. There was no clear-cut relationship between the cumulative dose and the responses. The main side-effect observed in 1 patient with widespread bone metastases after three doses (12.9 GBq) was a pancytopenia, which resolved after treatment was discontinued. This study suggests that repeated [131I]MIBG treatment could be effective in patients with advanced malignant pheochromocytoma.

Radiotoxicity of some iodine-123, iodine-125 and iodine-131-labeled compounds in mouse testes: implications for radiopharmaceutical design.

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).

Radiopharmaceutical treatment of malignant pheochromocytoma.

Apart from relieving effects of secreted catecholamines, treatments of malignant pheochromocytoma have achieved little success. When the radiopharmaceutical, meta-[131I] iodobenzylguanidine (I-131 MIBG ), was found to concentrate in some malignant pheochromocytomas, we calculated that this agent could impart therapeutic doses of radiation to these tumors. We therefore treated five patients with two to four doses of I-131 MIBG prepared in high specific activity, 8-11 Ci/mmol. Individual doses were given at 3- to 10-mo intervals and in 97- to 197-mCi amounts. Two patients exhibited subjective and objective benefits. Their tumors declined in size (to 28% and 30% of original volumes) and in hormone secretion (to 50% or less of baseline rates). The other three patients manifested few symptoms before treatment and showed few or no objective improvement afterward. The tumors of the patients who responded to I-131 MIBG (a) appeared to be more rapidly growing, (b) received more cumulative rads, and (c) were more predominantly in soft tissues (in contrast to bone) than those in the patients who obtained little benefit. No toxic effects were encountered during the treatments, and only minor and temporary untoward responses were seen later.

Iodine-131-metaiodobenzylguanidine dosimetry in cancer therapy: risk versus benefit.

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).

Scintigraphic localization of lymphatic leakage site after oral administration of iodine-123-IPPA.

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.

Gallbladder density and iodine concentration in humans during oral cholecystography. A comparison of iopanoic acid and iopronic acid.

A comparison of two oral cholecystopaques, iopanoic acid (Telepaque) and iopronic acid (Oravue), was performed using normal volunteers. Using a double-blind crossover design, comparisons were made between the degree of gallbladder opacification and the amount of iodine recovered from the gallbladder. Bile was collected via a double lumen intestinal tube before, during, and after stimulating gallbladder contraction. There were no differences between the two agents in terms of opacification or iodine concentration. Only 19% of the administered dose of either agent was recovered, and the maximum iodine concentration in bile was 10 mg I/ml. The results suggest that this technique has merit for future comparative studies of agents concentrated in the gallbladder.

Saturation kinetics of iocetamic acid: Evaluation of indirect pharmacokinetic techniques and comparison with iopanoic acid.

The biliary excretion of two oral cholecystographic contrast agents, iocetamic acid and iopanoic acid, were compared during low and high taurocholate infusion rates. The pharmacokinetics of these compounds after intravenous infusion were studied in bile-fistula dogs using both indirect and direct pharmacokinetic techniques. The indirect multiple infusion technique, corrected for urinary excretion, provides a reliable estimate of the maximum biliary excretion rates of either contrast agent without necessitating the sampling of biliary output. The results indicate that taurocholate facilitates the biliary excretion of both agents. At both taurocholate infusion rates studied, the maximum biliary excretion rate of iocetamic acid is greater than that of iopanoic acid.