H-FABP, cardiovascular risk factors, and functional status in asymptomatic spinal cord injury patients.

BACKGROUND: This was a cross-sectional study in the setting of a rehabilitation hospital. OBJECTIVE: The aim of the study was to determine the serum levels of heart-type fatty acid-binding protein (H-FABP) in patients with spinal cord injury (SCI). A further goal was to examine whether there is a relationship between H-FABP levels and Functional Ambulation Classification (FAC) scale, Functional Independence Measure (FIM) score, American Spinal Injury Association (ASIA) status, and metabolic syndrome (MetS). METHODS: The study included 56 SCI patients and 37 age- and sex-matched healthy control subjects who had not been diagnosed with coronary artery disease in the past. RESULTS: Serum H-FABP levels were significantly higher in patients with SCI than in control subjects: paraplegia group, 18.5 ± 11.4; tetraplegia group, 16.3 ± 9.1; control group, 6.7 ± 5.1 ng/ml (p < 0.001). There was no difference between the other cardiac enzymes (troponin I, AST, ALT, CK, CK-MB, and LDH) among the groups. The relationship between the serum H-FABP levels and FAC status was examined. There was a negative correlation between FAC status and H-FABP levels (p < 0.001, r = - 0.581). Patients with complete SCI were divided into two groups according to the level of the lesion: (lesion levels in C6-T6, n = 25; lesion levels in T7-L2, n = 11). In patients with complete motor injury, H-FABP levels were higher in subjects with injuries above T6 than in those with injuries below T6 (24.21 ± 10.1 and 14.1 ± 10.4, respectively; p = 0.011). Serum levels of H-FABP were higher in SCI patients with MetS (n = 10) than in those without MetS (n = 46; 25.8 ± 11.6 ng/ml vs. 16.42 ± 10.3 ng/ml, respectively; p = 0.014). Patients were then divided into two groups according to SCI duration: < 12 months (n = 27) and > 12 months (n = 29). H-FABP levels showed statistically significant differences between the two groups (14.8 ± 11.7 ng/dl and 20.9 ± 9.9 ng/dl, respectively; p = 0.036). CONCLUSION: H-FABP is related to MetS and FAC status in asymptomatic SCI patients.

Effects of extracorporal shock wave therapy on symptomatic heel spurs: a correlation between clinical outcome and radiologic changes.

Plantar heel pain, a chronic and disabling foot alignment, occurs in the adult population. Extracorporal shock wave therapy (ESWT) offers a nonsurgical option in addition to stretching exercises, heel cups, NSAI, and corticosteroid injections. This study aimed to investigate the effects of ESWT on calcaneal bone spurs and the correlation between clinical outcomes and radiologic changes. The study involved 108 patients with heel pain and radiologically diagnosed heel spurs. All patients underwent ESWT once a week for 5 weeks at the clinic. Each patient received 2,000 impulses of shock waves, starting with 0.05 mJ/mm2 (1.8 bar) and increasing to 0.4 mJ/mm2 (4.0 bar). Standard radiographies of the affected heels were obtained before and after the therapy. Clinical results demonstrated excellent (no pain) in 66.7% of the cases, good (50% of pain reduced) in 15.7% of the cases, and unsatisfactory (no reduction in pain) in 17.6%. After five ESWT treatments, no patients who received shock wave applications had significant spur reductions, but 19 patients (17.6%) had a decrease in the angle of the spur, 23 patients (21.3%) had a decrease in the dimensions of the spur, and one patient had a broken spur. Therefore, results showed no correlation between clinical outcome and radiologic changes. The present study supports the finding that even with no radiologic change after ESWT therapy, the therapy produces significant effects in reducing patients' complaints about heel spurs.

Incidence of acute hepatitis B in patients with spinal cord injury.

STUDY DESIGN: Retrospective case survey. OBJECTIVE: To examine incidence and clinical characteristics of hepatitis B infection in individuals with spinal cord injury (SCI). SETTING: Inpatient clinic within a physical medicine and rehabilitation hospital specialized in rehabilitation. PARTICIPANTS: A total of 161 patients with SCI. INTERVENTIONS: Patients' records were investigated and the status of hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), anti-hepatitis B surface antigen positivity, alanine aminotransferase levels, duration of hospitalization and cost were recorded. MAIN OUTCOME MEASURES: Incidence of acute hepatitis B. RESULTS: Six patients were diagnosed with acute hepatitis B on the first hospitalization for rehabilitation. A total of 11 patients (4.2%) were HBsAg positive with a previously established diagnosis of hepatitis B virus infection, 1 patient (0.4%) was anti-HCV positive. After a follow-up of 6 months, three of the acute hepatitis B patients progressed into chronic hepatitis B stage. In acute hepatitis B patients' initiation of the rehabilitation was delayed, duration of hospitalization was increased. CONCLUSIONS: After SCI, patients are at high risk of acute hepatitis B infection. A high rate of chronicity may be associated with impaired immune response, secondary to neurological deficit. Screening and vaccination protocols may prevent the spread of the hepatitis B infection, healthcare losses and financial loss.

Somatostatin receptor scintigraphy in primary cutaneous T- and B-cell lymphomas.

BACKGROUND: Monitoring and repeated staging is of substantial importance in many patients with primary cutaneous T-cell lymphomas (CTCL). For primary cutaneous B-cell lymphomas (CBCL), extensive initial staging is the mainstay for correct diagnosis. AIM: To evaluate the value of somatostatin receptor scintigraphy using the radiolabeled somatostatin analog (111)In-pentetreotide in comparison to conventional imaging methods for the staging of patients with primary CTCL and primary CBCL. METHODS: Twenty-two patients (15 patients with histologically verified CTCL and 7 patients with histologically verified CBCL) were included. Stage of disease was established by physical examination, laboratory screening, skin inspection, palpation of superficial lymph nodes, sonography and computed tomography (CT) in patients with advanced clinical stage. Focally elevated tracer uptake of (111)In-pentetreotide was compared to common imaging modalities, physical aspect and digital photographs of the respective skin lesions. RESULTS: Of the 15 patients with CTCL, only 4 (27%) showed positive scintigraphic results, but not in all sites of lymphomatous involvement. None of the five patients with mycosis fungoides in stage I, nor any of the four patients with Sézary syndrome, had a positive (111)In- pentetreotide scan. Of the seven patients with CBCL three positive scintigraphic results (43%) could be obtained: in two patients with a follicular center lymphoma and one patient with a diffuse large B-cell lymphoma - leg type, but again not in all apparent sites of lymphoma. CONCLUSIONS: Based on our results, we do not recommend the use of somatostatin receptor scintigraphy for routine staging of patients with CTCL and CBCL. As our series includes only 22 patients, and the number of patients with rarer variants of CTCL was rather small, it might be too premature to abandon SST-R in the staging of patients with cutaneous lymphomas.

Occupation in spinal cord injury patients in Turkey.

STUDY DESIGN: A cross-sectional survey. OBJECTIVES: To investigate the changes in the occupation of patients after spinal cord injury (SCI) and the factors that cause this change. SUBJECTS: The study involved 192 Turkish patients (41 female, 151 male) who had suffered SCI. The mean age of patients was 36.1+/-12.0 years. The mean follow-up time was 43.4+/-38.0 months. Before injury, 138 patients were employed in gainful occupations, 26 patients were housewives, 10 were retired, 7 were students and 11 patients were unemployed. Only 15 patients (7.8%) returned to their original occupations after injury. Thirteen patients (6.8%) are currently working in another job; 1 patient (0.5%) is a student; 10 (5.2%) are retired as was earlier; 40 (20.8%) are retired on grounds of disability; 26 (13.5%) are housewives; and 87 patients (45.3%) are currently unemployed. METHODS: Prospective data collection through a face-to-face interview on an established SCI Turkish sample. RESULTS: In our study, the rate of returning to work was found to be 14.6%. In the evaluation of factors affecting return to work after injury, educational level (P=0.00), pre-injury employment (P=0.01) and bladder-emptying method (P=0.03) were statistically significantly correlated with return to work. CONCLUSION: In this study, education, pre-injury employment and bladder-emptying method were found to be important factors in returning to work after SCI.

Value of peptide receptor scintigraphy using (123)I-vasoactive intestinal peptide and (111)In-DTPA-D-Phe1-octreotide in 194 carcinoid patients: Vienna University Experience, 1993 to 1998.

PURPOSE: To report our experience with both (123)I-vasoactive intestinal peptide (VIP) and (111)In-DTPA-D-Phe(1)-octreotide for imaging to identify primary and metastatic tumor sites in carcinoid patients. PATIENTS AND METHODS: One hundred ninety-four patients with a verified or clinically suspected diagnosis of a carcinoid tumor were injected with (111)In-DTPA-D-Phe(1)-OCT for imaging purposes, while 133 patients underwent scanning with both (123)I-VIP and (111)In-DTPA-D-Phe(1)-OCT in random order. Imaging results were compared with computed tomography scans, results of conventional ultrasound, endosonography, and endoscopy, and results of surgical exploration in case of inconclusive conventional imaging. RESULTS: Primary or recurrent carcinoid tumors could be visualized with (111)In-DTPA-D-Phe(1)-OCT in 95 (91%) of 104 patients; metastatic sites were identified in 110 (95%) of 116 patients. In 11 (51%) of 21 patients with suggestive symptoms but without identified lesions by conventional imaging, focal tracer uptake located the carcinoid tumor. In addition, metastatic disease was demonstrated in three patients after resection. In a direct comparison in the 133 patients who underwent both imaging modalities, (111)In-DTPA-D-Phe(1)-OCT was found to be superior to (123)I-VIP, with 35 (93%) of 38 versus 32 (82%) of 38 scans being positive in primary or recurrent tumors, 58 (90%) of 65 versus 53 (82%) of 65 being positive in patients with metastatic sites, and seven (44%) of 16 versus four (25%) of 16 being positive in patients with symptoms but otherwise negative work-ups. Overall, additional lesions not seen on conventional imaging were imaged in 43 (41%) of 158 versus 25 (25%) of 103 scans with (111)In-DTPA-D-Phe(1)-OCT and (123)I-VIP, respectively. CONCLUSION: Both peptide tracers have a high sensitivity for localizing tumor sites in patients with ascertained or suspected carcinoid tumors, with (111)In-DTPA-D-Phe(1)-OCT scintigraphy being more sensitive than (123)I-VIP receptor scanning. Both, however, had a higher diagnostic yield than conventional imaging, as verified by surgical intervention or long-term follow-up. The combination of both peptide receptor scans does not seem to further enhance diagnostic information.

Experience with indium-111 and yttrium-90-labeled somatostatin analogs.

The high level expression of somatostatin receptors (SSTR) on various tumor cells has provided the molecular basis for successful use of radiolabeled octreotide / lanreotide analogs as tumor tracers in nuclear medicine. Other (nontumoral) potential indications for SSTR scintigraphy are based on an increased lymphocyte binding at sites of inflammatory or immunologic diseases such as thyroid-associated ophthalmology. The vast majority of human tumors seem to over-express the one or the other of five distinct hSSTR subtype receptors. Whereas neuroendocrine tumors frequently overexpress hSSTR2, intestinal adenocarcinomas seem to overexpress more often hSSTR3 or hSSTR4, or both of these hSSTR. In contrast to In-DTPA-DPhe(1)-octreotide (OctreoScan(R)) which binds to hSSTR2 and 5 with high affinity (Kd 0.1-5 nM), to hSSTR3 with moderate affinity (K(d) 10-100 nM) and does not bind to hSSTR1 and hSSTR4, (111)In / (90)Y-DOTA-lanreotide was found to bind to hSSTR2, 3, 4, and 5 with high affinity, and to hSSTR1 with lower affinity (K(d) 200 nM). Based on its unique hSSTR binding profile, (111)In-DOTA-lanreotide was suggested to be a potential radioligand for tumor diagnosis, and (90)Y-DOTA-lanreotide suitable for receptor-mediated radionuclide therapy. As opposed to (111)In-DTPA-DPhe(1)-octreotide and (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide, discrepancies in the scintigraphic results were seen in about one third of (neuroendocrine) tumor patients concerning both the tumor uptake as well as detection of tumor lesions. On a molecular level, these discrepancies seem to be based on a "higherrdquuo; high-affinity binding of (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide to hSSTR2 (K(d) 0.1-1 nM). Other somatostatin analogs with divergent affinity to the five known hSSTR subtype receptors have also found their way into the clinics, such as (99m)Tc-depreotide (NeoSpect(R); NeoTect(R)). Most of the imaging results are reported for neuroendocrine tumors (octreotide analogs) or nonsmall cell lung cancer ((99m)Tc-depreotide), indicating high diagnostic cabability of this type of receptor tracers. Consequently to their use as receptor imaging agents, hSSTR recognizing radioligands have also been implemented for experimental receptor-targeted radionuclide therapy. Beneficial results were reported for high-dose treatment with (111)In-DTPA-DPhe(1)-octreotide, based on the emission of Auger electrons. The Phase IIa study "MAURITIUS" (Multicenter Analysis of a Universal Receptor Imaging and Treatment Initiative, a eUropean Study) showed in progressive cancer patients (therapy entry criteria) with a calculated tumor dose > 10 Gy / GBq (90)Y-DOTA-lanreotide, the proof-of-principle for treating tumor patients with peptide receptor imaging agents. In the "MAURITIUS" study, cummulative treatment doses up to 200 mCi (90)Y-DOTA-lanreotide were given as short-term infusion. Overall treatment results in 70 patients indicated stable tumor disease in 35% of patients and regressive tumor disease in 10% of tumor patients with different tumor entities expressing hSSTR. No acute or chronic severe hematological toxicity, change in renal or liver function parameters due to (90)Y-DOTA-lanreotide treatment, were reported. (90)Y-DOTA-DPhe(1)-Tyr(3)-octreotide may show a higher tumor uptake in neuroendocrine tumor lesions and may therefore be superior for treatment in patients with neuroendocrine tumors. However, there is only limited excess to long-term and survival data at present. Potential indications for (90Y-DOTA-lanreotide are radioiodine-negative thyroid cancer, hepatocellular cancer and lung cancer. Besides newer approaches and recent developments of 188)Re-labeled radioligands, no clinical results on the treatment response are yet available. In conclusion, several radioligands have been implemented on the basis of peptide receptor recognition throughout the last decade. A plentitude of preclinical data and clinical studies confirm their potential use in diagnosis as well as "proof-of-principle" for therapy of cancer patients. However, an optimal radiopeptide formulatioents. However, an optimal radiopeptide formulation does not yet exist for receptor-targeted radionuclide therapy. Ongoing developments may result in peptides more suitable for this kind of receptor-targeted radionuclide therapy.

Indium-111-DTPA-D-Phe-1-octreotide and technetium-99m-(V)-dimercaptosuccinic acid scanning in the preoperative staging of medullary thyroid carcinoma.

UNLABELLED: The early detection of all tumor sites in patients with medullary thyroid carcinoma (MTC) before primary surgery is important, because MTC tends to metastasize to regional lymph nodes of the neck and mediastinum early during the course of the disease. METHODS: In an approach to localize the primary tumor sites and to detect additional tumor involvement, we have performed in 22 patients with MTC either 99mTc(V)-dimercaptosuccinic acid (DMSA) and/or 111In-diethylenetriamine pentaacetic acid-D-Phe-1-octreotide scintigraphy. RESULTS: Indium-111-octreotide (150-200 MBq) identified the primary tumor in 10 of 14 patients (71%), whereas the primary tumor was visualized by 99mTc-DMSA (300-370 MBq) in 10 of 17 patients (58%). In 8 of 22 patients (36%), lymph node metastases were present at the time of diagnosis, as confirmed by histopathology and histochemistry after surgery (all <2 mm). Preoperatively, neither scan was able to detect lymph node involvement in these patients (0/8). CONCLUSION: Both 99mTc-DMSA and 111In-octreotide studies have similar sensitivity to localize primary MTC; however, these scans are not able to detect small lymph node involvement (micrometastases) before initial surgery. Unfortunately, both scans have no clinical implication for preoperative staging in patients with MTC.

Vasoactive intestinal peptide and somatostatin receptor scintigraphy for differential diagnosis of hepatic carcinoid metastasis.

We report a case of a hepatic carcinoid metastasis mimicking a hemangioma on ultrasound and on CT. Indium-111-DTPA-D-Phe-1-octreotide (111In-OCT) and 123I-vasoactive intestinal peptide (123I-VIP) receptor images suggested a carcinoid metastasis of the liver. The final diagnosis was established histopathologically. The differential diagnosis of liver lesions is discussed.

Distinction between hepatic focal nodular hyperplasia and malignant liver lesions using technetium-99m-galactosyl-neoglycoalbumin.

UNLABELLED: Distinction between hepatic focal nodular hyperplasia (FNH) and malignant liver lesions is essential because of the different therapy strategies, since FNH can be managed conservatively. The aim of this study was to describe the imaging pattern of FNH using the hepatocyte receptor ligand 99mTc-galactosyl-neoglycoalbumin 99mTc-NGA) and to assess the value of this receptor imaging agent in the differentiation of FNH from malignant liver lesions. METHODS: Twelve consecutive patients with histologically confirmed FNH were investigated. The FNH-lesions were asymptomatic and incidentally found by ultrasonography. Nine patients with histologically verified hepatocellular carcinomas and three patients with liver metastases spread from gastrointestinal adenocarcinomas served as controls. RESULTS: All FNH lesions showed normal or even increased uptake of 99mTc-NGA. Whereas malignant liver lesion-to-normal liver ratios amounted to 0.4 +/- 0.2 (mean +/- s.d.), FNH lesion-to-normal liver ratios were 1.7 +/- 0.3 (mean +/- s.d.). CONCLUSION: The receptor imaging agent 99mTc-NGA with concurrent use of SPECT is useful in the differential diagnosis of FNH and malignant hepatic tumors.

Inhalation scintigraphy with iodine-123-labeled interferon gamma-1b: pulmonary deposition and dose escalation study in healthy volunteers.

UNLABELLED: Recent studies have suggested that recombinant interferon gamma (IFNg) may be useful in the treatment of various respiratory diseases, such as chronic inflammatory disease. This study was undertaken to investigate the dose response of escalating doses of inhaled 123I-labeled IFNg (123I-IFNg) and its safety, biodistribution and radiation absorbed doses in healthy volunteers. METHODS: IFNg was labeled with 123I to produce a specific activity of 1800 MBq/mg of IFNg. The biological activities of 123I-IFNg, nebulized 123I-IFNg and unlabeled IFNg were evaluated in various functional in vitro tests. Ten healthy volunteers were enrolled in the in vivo dose escalation study (180 MBq of 123I-IFNg diluted with 0.1-2 mg of INFg). Inhalation scintigraphy, using a Pari-Master nebulizer, was performed for up to 37 min, during which dynamic posterior images of the lungs were obtained. Whole-body scanning was performed at various time points up to 24 hr postinjection, for biodistribution and dosimetry purposes. Blood, urine and feces were also collected over this 24-hr period. Lung perfusion scintigraphy with 99mTc-microspheres was performed at the end of the study for attenuation correction. RESULTS: Inhaled nebulized IFNg showed a uniform deposition pattern in the lungs with deposition ratios of 0.74 (central-to-peripheral) and 0.78 (upper-to-lower). The lung deposition of IFNg was time-dependent, with a deposition half-time between 1 and 5 min. Despite a large interindividual variation, the total lung deposition was proportional to the nebulizer charge and was 53 +/- 12% of the inhaled dose and 19 +/- 7% of the initial nebulizer charge (between 0.1 and 2 mg of IFNg). The biological half-life in the lung could be fitted to a biexponential function, with resultant half-lives of 1 and 11 hr. Blood activity was maximal at 3.5 hr after inhalation and was due to free iodine. The radioactivity was excreted through both the urinary and intestinal tracts. Plasma IFNg levels did not significantly increase over time, and no significant HLA-DR induction on peripheral blood cells was detected. The highest radiation absorbed doses of 0.14 and 0.19 mGy/MBq were determined for the trachea and the lower intestines, respectively. The effective dose equivalent was 0.05 mSv/MBq. CONCLUSION: After inhalation with the Pari-Master nebulizer, IFNg deposits normally in the lungs and shows no systemic effects in healthy volunteers.

Response to treatment with yttrium 90-DOTA-lanreotide of a patient with metastatic gastrinoma.

1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid (DOTA)-lanreotide is a universal somatostatin (SST) receptor subtype ligand that binds to a large variety of human tumors. We report the case of a patient with metastatic gastrinoma who was treated with 90Y-DOTA-lanreotide. Before treatment, dosimetry with 111In-DOTA-lanreotide (150 MBq, 10 nmol) indicated a dose of 5.8 mGy/MBq for the recurrent abdominal gastrinoma, and a mean dose of approximately 1.0 mGy/MBq for liver metastases (i.e., 56 and approximately 10 mGy/MBq for 90Y-DOTA-lanreotide, respectively). After four infusions of 90Y-DOTA-lanreotide (each 1 GBq, approximately 30 nmol) over a 6-mo period, the 111In-DOTA-lanreotide scintigraphy of the liver had returned to a nearly normal condition and a remarkably decreased uptake by the recurrent gastrinoma was calculated (approximately 5 mGy/MBq for 90Y-DOTA-lanreotide). The imaging results were well-correlated with a 25% regression of the liver metastases as indicated by CT. Blood, urine and whole-body clearances of 111In-DOTA-lanreotide and 90Y-DOTA-lanreotide were very similar. The DOTA-lanreotide promises to be useful for functional tumor diagnosis (111In-DOTA-lanreotide) and receptor-mediated tumor radiotherapy (90Y-DOTA-lanreotide).

Iodine-123-vasoactive intestinal peptide receptor scanning in patients with pancreatic cancer.

UNLABELLED: Recent data demonstrated a high sensitivity (>90%) in the visualization of primary/recurrent pancreatic cancer as well as metastases by means of 123I-labeled vasoactive intestinal peptide (VIP). The aim of this study was to investigate the diagnostic value of radioiodinated VIP in patients suffering from adenocarcinoma of the exocrine pancreas. METHODS: Sixty consecutive patients (26 women, 34 men; mean age 59 yr) with histologically verified pancreatic cancer were investigated in this study. Twenty-one patients presented with organ-confined malignancy (19 at study entry and 2 during follow-up after initial surgery developed tumor recurrence), while 25 patients had distant metastases along with the local malignancy, and 7 patients had liver metastases after resection of the primary lesion (6 on study entry and 1 during follow-up showed tumor development). In 5 of these patients, abdominal lymph node metastases were present at the time of scanning. Of 10 patients, who had undergone potentially curative surgery for their cancer, 7 remained free of disease during follow-up until death or for at least 6 mo. Iodine-123-VIP (150-200 MBq; approximately 1 microg VIP) was administered to all patients. Scintigraphic results were evaluated as compared to conventional radiologic imaging methods and surgical exploration. RESULTS: Primary pancreatic tumors were visualized by 123I-VIP in 19/21 patients (90%) with disease confined to the pancreas and in 8/25 patients (32%) suffering both from locoregional and disease metastatic to the liver. The overall 123I-VIP scan sensitivity for primary pancreatic adenocarcinomas was 58% (27/46 scans). Liver metastases were imaged in 29/32 patients (scan sensitivity 90%) and abdominal lymph node metastases in 4/5 patients. In 5 patients, the VIP receptor scan indicated the malignant lesion before CT. In vitro results confirmed specific binding of 123I-VIP to primary pancreatic tumor cells as well as to PANC1 adenocarcinoma cells. CONCLUSION: Iodine-123-VIP receptor scanning has the potential to offer additional information to augment diagnostic standard methods and could influence the decision-making process in the treatment of pancreatic cancer.

Location of a VIPoma by iodine-123-vasoactive intestinal peptide scintigraphy.

A major problem in patients with small endocrine tumors is the difficulty in localizing the primary tumor site. Many endocrine tumors possess larger amounts of high affinity vasoactive intestinal peptide (VIP) binding sites compared with normal tissue or blood cells. We used radiolabeled VIP to localize the tumor site in a patient with Verner-Morrison syndrome (VMS). Under octreotide therapy, the VIP levels had declined in this patient, but a tumor site could not be detected by conventional techniques or by radiolabeled octreotide. However, using 123I-VIP, the tumor was detectable in the pancreatic tail. Surgical resection of the tumor was followed by complete remission of the VMS. Expression of VIP binding sites in the tumor was confirmed by a radioreceptor assay and showed cross-competition between VIP and octreotide. The identity of the VIP binding site in the tumor was analyzed by Northern blotting and revealed the expression of somatostatin receptor subtype 3, which binds both somatostatin-14 and VIP with higher affinity than octreotide. Iodine-123-VIP scintigraphy would be an effective tracer to identity the tumor site in VMS patients.

Vasoactive intestinal peptide receptor scintigraphy.

UNLABELLED: This study presents the biodistribution, safety and absorbed dose of 123I-VIP administered to 18 patients with intestinal adenocarcinomas or endocrine tumors. METHODS: To achieve high-specific activity, 123I-VIP was purified by HPLC. Following intravenous administration of 123I-VIP (172 +/- 17 MBq (4.65 +/- 0.5 mCi); < 300 pmole ( < 1 microgram)/patient), sequential images were recorded during the initial 30 min. Thereafter, whole-body images were acquired in anterior and posterior views at various time points. Dosimetry calculations were performed on the basis of gamma camera data, urine, feces and blood activities. RESULTS: After injection of labeled peptide, the lung was the primary site of 123I-VIP uptake. Peak lung activity represented 40% +/- 7% of the injected dose at 0.7 hr and declined to 21% +/- 7% at 3.5, to 14% +/- 3% at 7 and to 8% +/- 4% 22 hr postinjection. Radioactivity was excreted into the urine and amounted to 37% +/- 16% of the injected dose within 4, 68% +/- 12% within 8, 82% +/- 16% within 16 and 93% +/- 8% within 24 hr postinjection. The mean effective half-life of 123I-VIP in the lungs was 2.2 and 6 hr in the urinary bladder. The highest radiation absorbed doses were calculated for the lungs [67 muGy/MBq (248 mrad/mCi)], urinary bladder [77 muGy/MBq (284 mrad/mCi)] and thyroid gland [104 muGy/MBq (386 mrad/mCi)]. The effective dose was 28 muSv/MBq (104 mrem/mCi). CONCLUSION: HPLC-purified 123I-VIP shows favorable dosimetry and is a safe and promising peptide tracer for localization of tumors expressing receptors for VIP.

Technetium-99m-galactosyl-neoglycoalbumin combined with iodine-123-Tyr-(A14)-insulin visualizes human hepatocellular carcinomas.

UNLABELLED: Human hepatocellular carcinoma (HCC) is the most frequent primary hepatic malignancy and its diagnosis by conventional methods is still difficult. We hypothesized that the expression of specific receptors could possibly be used to improve in vivo localization of HCC with specific receptor-based radioligands. METHODS: In initial in vitro studies, receptor binding of 99mTc-galactosyl-neoglycoalbumin (99mTc-NGA) and 123I-Tyr-(A14)-insulin to HCC was investigated. Scintigraphy was performed in 45 patients with histologically confirmed HCC using either 99mTc-NGA (75-150 MBq; 25-50 nmole, n = 27) and/or 123I-Tyr-(A14)-insulin (100-150 MBq; 7.5-10 micrograms, n = 30). RESULTS: HCC (1256 +/- 290 pmole bound/mg protein, Kd = 3.4 +/- 2.9 nM) expressed a 1000-fold higher number of specific receptors for 123I-Tyr-(A14)-insulin compared to normal liver tissue (2.4 +/- 0.8 pmole bound/mg protein, Kd = 4.2 +/- 2.4 nM), whereas HCC did not express receptors specific for 99mTc-NGA. All HCC lesions were identified as cold spots after injection of 99mTc-NGA, whereas 123I-Tyr-(A14)-insulin accumulated in these lesions, indicating HCC-to-normal liver ratios of 1.6 +/- 0.4 in the mean. Subtraction images obtained from planar studies visualized 123I-Tyr-(A14)-insulin in HCC lesions detected by 99mTc-NGA as cold spots. CONCLUSION: This hepatocyte receptor-specific, double-tracer method using 99mTc-NGA and 123I-Tyr-(A14)-insulin could become clinically useful in the diagnosis of HCC.

Comparison of iodine-123-vasoactive intestinal peptide receptor scintigraphy and indium-111-CYT-103 immunoscintigraphy.

UNLABELLED: Recently, we have shown that the expression of receptors for vasoactive intestinal peptide (VIP) on intestinal adenocarcinomas can be used for in vivo targeting of primary or metastatic tumor sites using 123I-labeled VIP. Several other receptors and antigens including the TAG-72 protein have also been implemented for in vivo localization purposes. In this study, we have compared the in vitro and in vivo binding of 123I-VIP and of the 111In-labeled monoclonal antibody (MAb) directed against TAG-72 (OncoScint; 111In-CR-103) in patients with intestinal adenocarcinomas in a single-blinded, prospectively randomized trial. METHODS: Twenty patients were administered either 123I-VIP (150-200 MBq; 1 microgram) or 111In-CYT-103 (150 MBq; 1 mg) for one imaging study. After interim analysis demonstrated superior imaging with 123I-VIP, the next 10 patients (accounting for a total of 50 patients) enrolled in this trial underwent both studies in random order to allow for a direct comparison. RESULTS: In total, 123I-VIP scans were true-positive in 28 of 30 patients (93%) versus 17 of 30 patients administered 111In-CYT-103 (56%). In the subgroup of 10 patients enrolled in the second part of the study, primary intestinal adenocarcinomas were imaged in five of five patients with 123I-VIP and in only two of these patients with 111In-CYT-103. Liver metastases were visualized in five of six patients by 123I-VIP receptor scanning and in four of these patients with 111In-CYT-103. The in vitro results indicated significant binding of 123I-VIP to primary colorectal tumors as well as to HT29 and COLO320 adenocarcinoma cells. In vitro, adenocarcinoma cells also expressed abundant numbers of the TAG-72 antigen. CONCLUSION: Intestinal adenocarcinomas co-express VIP receptors and the IAG-72 antigen. Despite significant in vitro binding of both agents, however, the VIP receptor scan is more sensitive in localizing intestinal adenocarcinomas and metastatic spread.

111In-DOTA-lanreotide scintigraphy in patients with tumors of the lung.

UNLABELLED: Imaging with radiolabeled somatostatin (SST) analogs has recently been established for the localization of various human SST receptor (hsstr)-positive tumors, including neuroendocrine tumors, lymphomas, and non-small cell lung cancer (NSCLC). METHODS: 111In-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid-lanreotide (DOTA-LAN) scintigraphy (150 MBq; 7 nmol per patient) was performed on 47 patients (28 patients with primary tumors, 19 patients with lung metastases from other tumors) to evaluate the tumor binding in patients with histologically confirmed lung cancer. A group of 27 tumor patients without documented lung lesions served as the control group. Early and delayed planar and SPECT images were acquired. Whole-body scintigraphy was performed at 0.5, 4-6, 24, and 48 h after injection for tumor dose estimation. In addition, hsstr subtype expression and radioligand binding characteristics were studied in vitro using lung tumor samples (n = 15). RESULTS: 111In-DOTA-LAN indicated the primary lung tumor in 16 of 16 NSCLC patients. Lymph node metastases were visualized in 6 of 6 NSCLC patients, and bone metastases were seen in 3 of 3 NSCLC patients. 111In-DOTA-LAN scintigraphy indicated lung carcinoid in 5 of 5 patients and small cell lung cancer lesions in 6 of 6 patients. Multiple lung metastases were shown in all 6 patients with non-Hodgkin's lymphoma and in the 1 patient with Hodgkin's disease, 5 of 5 colorectal adenocarcinoma patients, 4 of 4 carcinoid patients, 2 of 2 neuroendocrine carcinoma (NEC) patients, and 1 of 1 angiosarcoma patient. Pulmonary tumor sites not indicated by CT or MRI were visualized in 6 of 47 tumor patients (i.e., 13%; lung metastases in 1 carcinoid patient and 1 NEC patient, lymph node metastases in 1 carcinoid patient and 2 NSCLC patients, bone metastases in 1 carcinoid patient). The estimated lung tumor dose ranged between 0.2 and 5 mGy/MBq. Focal lung uptake of 111In-DOTA-LAN was not observed in any of the 27 control patients. In vitro binding studies indicated high-affinity binding sites for 111In-DOTA-LAN in NSCLC samples (dissociation constants, 0.5 and 4 nmol/L) with predominant expression of hsstr4. CONCLUSION: 111In-DOTA-LAN yields high tumor binding for various human lung tumors. Consecutively, radiopeptide therapy may offer a potential new treatment alternative for some lung tumor patients.

Indium-111-DOTA-lanreotide: biodistribution, safety and radiation absorbed dose in tumor patients.

UNLABELLED: Imaging with radiolabeled somatostatin/vasoactive intestinal peptide analogs has recently been established for the localization diagnosis of a variety of human tumors including neuroendocrine tumors, intestinal adenocarcinomas and lymphomas. This study reports on the biodistribution, safety and radiation absorbed dose of 111In-1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid (DOTA)-lanreotide, a novel peptide tracer, which identifies hSST receptor (R) subtypes 2 through 5 with high affinity, and hSSTR1 with low affinity. METHODS: The tumor localizing capacity of 111In-DOTA-lanreotide was initially investigated in 10 patients (3 lymphomas, 5 carcinoids and 2 intestinal adenocarcinomas). Indium-111 -DOTA-lanreotide was then administered to 14 cancer patients evaluated for possible radiotherapy with 90Y-DOTA-lanreotide (8 neuroendocrine tumors, 4 intestinal adenocarcinomas, 1 Hodgkin lymphoma and 1 prostate cancer). After intravenous administration of 111In-DOTA-lanreotide (approximately = 150 MBq; 10 nmol/patient), sequential images over one-known tumor site were recorded during the initial 30 min after peptide application. Thereafter, whole-body images were acquired in anterior and posterior views up to 72 hr postinjection. Dosimetry calculations were performed on the basis of scintigraphic data, urine, feces and blood activities. A comparison with 111In-DTPA-D-Phe1-octreotide (111In-OCT) scintigraphy was performed in 8 of the patients. RESULTS: After an initial rapid blood clearance [results of biexponential fits: T(eff1) 0.4 min (fraction a1 80%) and T(eff2) 13 min (fraction a2 14%)], the radioactivity was excreted into the urine and amounted to 42% +/- 3% of the injected dose (%ID) within 24 hr and 62% +/- 6%ID within 72 hr after injection of 111In-DOTA-lanreotide. In all patients, tumor sites were visualized during the initial minutes after injection of 111In-DOTA-lanreotide. The mean radiation absorbed dose amounted to 1.2 (range 0.21-5.8) mGy/MBq for primary tumors and/or metastases. The effective half-lives of 111In-DOTA-lanreotide in the tumors were T(eff1) 4.9 +/- 2.2 and T(eff2) 37.6 +/- 6.6 hr, and the mean residence time tau was 1.8 hr. The highest radiation absorbed doses were calculated for the spleen (0.39 +/- 0.13 mGy/MBq), kidneys (0.34 +/- 0.08 mGy/MBq), urinary bladder (0.21 +/- 0.03 mGy/MBq) and liver (0.16 +/- 0.04 mGy/MBq). The effective dose was 0.11 +/- 0.01 (range 0.09-0.12) mSv/MBq. During the observation period of 72 hr, no side effects were noted after 111In-DOTA-lanreotide application. The 111In-DOTA-lanreotide radiation absorbed tumor dose was significantly higher (ratio 2.25 +/- 0.60, p < 0.01) when directly compared with 111In-OCT. CONCLUSION: Indium-111 -DOTA-lanreotide shows a high tumor uptake for a variety of different human tumor types, has a favorable dosimetry over 111In-OCT and is clinically safe.

Treatment of hepatocellular cancer with the long acting somatostatin analog lanreotide in vitro and in vivo.

Based on the fact that somatostatin (SST) analogs have given promising results for treatment of hepatocellular cancer, we performed both in vitro and in vivo investigations to define the role of a depot formulation of the long acting SST-analog lanreotide (LAN). A decrease of cells in the S-phase as compared to controls (p<0.03) followed by a significant, dose-dependent induction of apoptosis could be demonstrated in Hep G2 cells along with a dose-dependent influence of the peptide on cellular proliferation. Northern blotting demonstrated the presence of mRNA for SSTR subtypes 2, 3 and 4 in Hep G2 cells, but only slight SSTR expression in normal liver tissue. In addition, 21 untreated patients with advanced HCC not amenable to surgery were administered 30 mg of LAN by deep intramuscular injection every 14 days until documented disease progression. Fifteen of these patients also underwent scanning with commercially available 111In-DTPA-D-Phe1-Octreotide (111In-OCT) to define the in vivo expression of SSTR. No positive 111In-OCT scans were obtained, indicating the absence of relevant amounts of functional SSTR2 in HCC. One patient (5%) showed a partial response to treatment, 8 patients had stable disease (38%), while the remaining patients progressed during treatment. The median survival was 4.2 months (range 1.2-13+), and the median time to progression was 2.5 months (range, 1.5-7+). However, 4 patients (19%) had an increase in WHO performance status lasting between 2.5 and 6 months, 5 patients (24%) had an increase in body weight, while pain markedly improved in 1 additional patient (5%). In total, 5 patients (24%) had a decrease in serum-AFP levels by at least 30%. Our results clearly indicate the ability of LAN to decrease the S-phase fraction along with induction of apoptosis in Hep G2 cells in a dose-dependent manner. Our data suggest clinical potential of SST-analogs in HCC and indicate that suboptimal doses of the peptide might have been administered in our series.