Biomedical subjects

I Virgolini

Publications and source records attributed to I Virgolini.

At least 55 records · Page 3Linked to original sources

PubMed1997

Mack Forster Award Lecture. Receptor nuclear medicine: vasointestinal peptide and somatostatin receptor scintigraphy for diagnosis and treatment of tumour patients.

The multiple aspects of radioligand-receptor interactions do not only show a major impact of certain cell surface-bound receptors in the pathophysiology of human disease: the concept of radioligand-receptor interactions has also been extended to the clinic. In particular, naturally occurring peptides, when radiolabelled, are clinically useful for the imaging diagnosis of human disease and have future implications for the treatment of tumour expressing certain target receptors using radiolabelled peptide tracers. The finding that receptors for VIP (vasoactive intestinal peptide) and SST (somatostatin) are overexpressed on tumour cells presents a breakthrough into this direction. Recent data indicate that [123I]-VIP receptor scintigraphy is clinically useful for the in vivo localization of small primary adenocarcinomas, liver metastases and certain endocrine tumours of the gastrointestinal tract. After the successful clinical introduction of the SST analogues [123I]-Tyr3-octreotide and [111In]-DTPA-D-Phe1-octreotide for localization diagnosis of neuroendocrine tumours in 1989, P829, labelled with the more cost-effective radionuclide 99mTc, nowadays promises to be a potential novel diagnostic imaging agent for tumours expressing SST/VIP receptors. Furthermore, the novel SST analogue [90Y]-MAURITIUS is entering the clinic for treatment of VIP/SST receptor-expressing tumours.

Adenocarcinoma↗

PubMed1997

Modified LDL decreases the binding of prostaglandin E2, I2, and E1 onto monocytes in patients with peripheral vascular disease.

Recent data suggest that various eicosanoids including prostaglandins play an important regulatory role in the development of atherosclerotic lesions. Peripheral blood monocytes have been implemented in early atherogenesis because they express receptors specific for modified LDL. In this study we investigated the binding of tritium prostaglandins E2 (3H-PGE2), E1 (3H-PGE1) and I2 (3H-PGI2) onto intact peripheral monocytes isolated from 20 patients (32-71 years) with manifested ischemic peripheral vascular disease stage II according to Fontaine and compared the results with those obtained in 16 healthy volunteers (21-68 years). In control subjects, Scatchard analyses of the binding data indicated a single class of high-affinity binding sites for 3H-PGE2 (maximal binding capacity [Bmax] = 11,400 +/- 3200 sites/cell; dissociation constant [Kd] = 1.3 +/- 0.5 nmol/L) and two classes of binding sites for 3H-PGE1 (Bmax1 = 11,200 +/- 4900 sites/cell, Kd1 = 1.5 +/- 0.5 nmol/L; Bmax2 = 47,800 +/- 6100 sites/cell, Kd2 = 12.8 +/- 5.9 nmol/L) as well as for 3H-PGI2 (Bmax1 = 10,100 +/- 3700 sites/cell, Kd1 = 1.7 +/- 0.7 nmol/L; Bmax2 = 81,200 +/- 5200 sites/cell, Kd2 = 14.2 +/- 6.5 nmol/L). In the patients, an absence of the higher-affinity binding class and significantly (P < .01) fewer lower-affinity binding sites were found for each ligand (PGE2: Bmax = 6600 +/- 3600 sites/cell, Kd = 12.1 +/- 3.2 nmol/L; PGI2: Bmax = 6400 +/- 3100 sites/cell, Kd = 22.1 +/- 8.3; PGE1: Bmax = 5300 +/- 1700 sites/ cell, Kd = 20.5 +/- 7.0 nmol/L). After incubation of monocytes with modified LDL (oxidized LDL or acetylated LDL), the binding of prostaglandins was significantly (P < .01 to P < .001) decreased, whereas native VLDL, LDL, and HDL did not interfere with prostaglandin binding. Prostaglandin-induced adenosine 3'-5' cyclic monophosphate (cAMP) formation by monocytes was significantly (P < .01) lower in patients (the concentrations causing 50% elevation of basal cAMP formation [ED50] were 3.8 +/- 2.4 nmol/L for PGE2, 6.3 +/- 3.5 nmol/L for PGE1, and 5.6 +/- 4.1 nmol/L for PGI2) than in the control subjects (ED50 was 1.6 +/- 1.2 nmol/L for PGE2, 4.8 +/- 2.5 nmol/L for PGE1, and 3.1 +/- 1.4 nmol/L for PGI2). After preincubation with modified LDL, the PG-induced cAMP production by monocytes was remarkably decreased in both patients and control subjects (P < .05). Our results suggest a direct effect of modified LDL on PGE2, PGE1, and PGI2 binding onto monocytes by reducing the number of cell surface-expressed receptors available. Modified LDL also reduces the sensitivity of monocytes to prostaglandins, which results in decreased cAMP production. The complex interactions between prostaglandins and lipoproteins may play an important role during atherogenesis.

Adult↗

PubMed1997

[Radiation exposure in the surrounding of patients after 201Tl myocardial scintigraphy].

AIM: It was the aim of the study to assess the additional radiation exposure to patients, attendants and nurses by patients who are undergoing nuclear medicine investigations (myocardial scintigraphy) with 201TL-chloride (201TL-CL). METHOD: In 16 cases the dose rates at 0.5 1 and 2 m distance from patients were measured at 0.5, 1.5, 3-4 and 24, in some cases until 370 h after administration of 100 +/- 10 MBq 201TL-CL. From the time courses of the dose rates around the patients the possible radiation exposure of other persons were estimated. RESULTS: The initial values of the dose rate were 3.82 microSv/h at 0.5 m, 1.18 microSv/h at 1 m and 0.30 microSv/h at 2 m distance from the patients respectively. The dose rates were decreasing following a monoexponential course with an effective half-life of 60 h. The maximum doses to other persons at 1 m distance from the patients were determined by considering three scenarios. The values were 13 microSv in the waiting room, 26 microSv for nurses, working in the ward and 105 microSv for persons living in the same house hold CONCLUSION: Even at very restrictive assumptions the closes were far below the maximum permissible dose to non-radiation workers see by radiation protection regulations (1.5 mSv per year).

Allied Health Personnel↗

PubMed1997

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.

Carcinoid Tumor↗

PubMed1997

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.

Administration, Inhalation↗

PubMed1997

[How great is radiation exposure in the area surrounding patients after administration ov 99mTc-sestamibi?].

AIM: The aim of the present study was to estimate the additional radiation exposure to personnel, other patients and members of the family caused by patients who had been injected with 99mTc-Sestamibi (Cardiolite DuPONT PHARMA) for preoperative localization of parathyroid adenoma. METHODS: Dose rates were measured from 16 patients who had received an intravenous injection of 600 +/- 50 MBq 99mTc-Sestamibi. All measurements were performed with a portable dosimeter (Berthold LB 133) at 3 different distances (0.5, 1 and 2 m) at 10 min, 180-200 min and 24 h after administration of the tracer. RESULTS: The dose rates amounted to 20.5 microSv/h at 0.5 m, 5.25 microSv/h at 1 m and 1.55 microSv/h at 2 m distance from patients respectively. The biological half-life was 54 h. The calculated maximal dose to other persons in the waiting area was 31.2 microSv, to family members 27.6 microSv and to nurses in a ward 31.2 microSv. CONCLUSION: Our results indicate that the calculated maximal radiation exposure for personnel, family members and other patients even under very unfavourable conditions was below the maximal allowed dose for non-professionally exposed persons.

Adenoma↗

PubMed1997

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.

Adult↗

PubMed1996

Interleukin 10 inhibits growth and granulocyte/macrophage colony-stimulating factor production in chronic myelomonocytic leukemia cells.

Autonomous release of hematopoietic growth factors may play a crucial role in the pathogenesis of certain hematological malignancies. Because of its cytokine synthesis-inhibiting action, interleukin 10 (IL-10) could be a potentially useful molecule to affect leukemic cell growth in such disorders. Chronic myelomonocytic leukemia (CMML) cells spontaneously form myeloid colonies (colony-forming units-granulocyte/macrophage) in methylcellulose, suggesting an autocrine growth factor-mediated mechanism. We studied the effect of recombinant human IL-10 (rhIL-10) on the in vitro growth of mononuclear cells obtained from peripheral blood or bone marrow of patients with CMML. IL-10 specifically binding to leukemic cells had a profound and dose-dependent inhibitory effect on autonomous in vitro growth of CMML cells. IL-10 significantly inhibited the spontaneous growth of myeloid colonies in methylcellulose in 10/11 patients, and autonomous CMML cell growth in suspension in 5/5 patients tested. Spontaneous colony growth from CMML cells was also markedly reduced by addition of antigranulocyte/macrophage colony-stimulating factor (GM-CSF) antibodies, but not by addition of antibodies against G-CSF, IL-3, or IL-6, IL-10-induced suppression of CMML cell growth was reversed by the addition of exogenous GM-CSF and correlated with a substantial decrease in GM-CSF production by leukemic cells, both at the mRNA and protein levels. Our data indicate that IL-10 profoundly inhibits the autonomous growth of CMML cells in vitro most likely through suppression of endogenous GM-CSF release. This observation suggests therapeutic evaluation of rhIL-10 in patients with CMML.

Aged↗

PubMed1996

Comparison of four rapid D-Dimer tests for diagnosis of pulmonary embolism.

Aim of this study was to evaluate rapid D-Dimer tests for their utility in diagnosis of acute pulmonary embolism (PE). Tests were performed in 183 consecutive pats referred for lung scanning because of clinically suspected PE. According to lung scans and the clinical course of disease 19 pats were classified to have PE with high probability and 164 with low probability. An ELISA (Agen) was used as the D-Dimer reference, and results compared with those of a turbidimetric (Behring), an immunofiltration (Nycomed), latex plasma and whole blood agglutination test (both Agen). There was a poor correlation between the turbidimetric test and either the ELISA (R = 0.38) and immunofiltration test (R = 0.49). The correlation between the ELISA and immunofiltration test was better (R = 0.73). The qualitative latex and whole blood agglutination tests were better fitted to ELISA since positive and negative samples were overlapped only in their 1st and 9th percentiles of ELISA values. The whole blood agglutination test was positive at lower ELISA values than the latex test. The highest sensitivity test for PE was the immunofiltration test (95%) (500ng/mL cut-off), followed by the turbidimetric method (89%) (66ng/mL), the ELISA (89%) (300ng/mL), the whole blood test (88%) and the latex test (68%). Specificity was lowest for the immunofiltration test (33%), intermediate (57-65%) for the turbidimetric and whole blood agglutination tests, and highest for the ELISA and the most insensitive latex test (76/77%). The whole blood assay was found to be the fastest and most suitable for bed site testing but weak positives were difficult to read. The immunofiltration test required plasma preparation but allowed objective semiquantitation of results. The less rapid turbidimetric assay was fully quantitative and objective.

Adolescent↗

PubMed1996

In vitro and in vivo studies of three radiolabelled somatostatin analogues: 123I-octreotide (OCT), 123I-Tyr-3-OCT and 111In-DTPA-D-Phe-1-OCT.

Scintigraphy with long-acting somatostatin (SST) analogues may be useful for the localization of tumours expressing receptors (R) for SST. In this study we have analysed the in vitro and in vivo binding properties of three SST analogues, 123I-octreotide (OCT), 123I-Tyr-3-OCT and 111In-DTPA-d-Phe-1-OCT. In vitro binding studies performed with a variety of primary tumours (n=48) as well as with several tumour cell lines (A431, HT29, PANC1, COLO320, HMC1, KU812) indicated significant in vitro binding of these three radiolabelled SST analogues to two subpopulations of SSTR, high (Kd 0.2-2.0 nM) and low (Kd 5-15 nM) affinity ones. The number of SSTR on tumour cells was at least a 1000-fold higher as compared with normal peripheral blood cells. Comparative scintigraphic studies using 123I-OCT and/or 123I-Tyr-3-OCT and/or 111In-DTPA-d-Phe-1-OCT were performed in 21 patients with histologically verified intestinal carcinoid tumours. Corresponding scintigraphic results were obtained in 18 of 21 patients investigated with two different SSTR ligands, either 123I-OCT/123I-Tyr-3-OCT (four of five), 123I-OCT/111In-DTPA-d-Phe-1-OCT (eight of nine), or 123I-Tyr-3-OCT/111In-DTPA-d-Phe-1-OCT (six of seven). We conclude that various tumours express high amounts of SSTR which are recognized by three radiolabelled SST analogues: 123I-OCT, 123I-Tyr-3-OCT and 111In-DTPA-d-Phe-1-OCT. Differences between these SST analogues in their in vitro binding and/or in vivo scanning properties are observed in a minority of patients. Thus, the labelling of OCT with iodine may be an alternative approach for those nuclear medicine departments for which 111In-DTPA-d-Phe-1-OCT is not easily available, or is too expensive.

Adolescent↗

PubMed1996

Prostaglandin E1 increases binding of 123I-low-density lipoprotein to the human liver in vivo.

Previous in vitro radioligand binding data have shown that prostaglandin E1 (PGE1) increases the number and the binding affinity of low-density lipoprotein (LDL) receptors of the human liver. Experimental data in normo- and hypercholesterolaemic rabbits have confirmed these findings, showing a significant increase in LDL-binding to the liver in vivo after prolonged PGE1 therapy. METHODS. This study aimed to confirm the experimental and animal data in human in vivo. 123I-LDL binding to the liver was quantified in vivo in patients suffering from peripheral vascular disease, seven of them with heterozygous familial hypercholesterolaemia (HC) and five with normal total plasma cholesterol, after PGE1 administration (5 ng.kg-1.min-1; 6 h daily for 5 days/week for 5 weeks). LDL uptake by the liver was quantified by single photon emission computer tomography (SPECT). RESULTS. The amount of LDL trapped by the liver in normocholesterolaemics (45.6%) was significantly higher than in hypercholesterolaemics (22.0%). PGE1 induced an increase in liver LDL binding, which was more pronounced in HC (+38.2%) than in normocholesterolaemic patients (+8.11%).

Aged↗

PubMed1996

Ibuprofen inhibits pyrogen-dependent expression of VCAM-1 and ICAM-1 on human endothelial cells.

Leukocyte adhesion and transmigration through the endothelial cell (EC) layer plays a crucial role in inflammation. IL-1 alpha and TNF alpha increase EC-adhesiveness for leukocytes by stimulating surface expression of ICAM-1 (intercellular adhesion molecule 1, CD54), VCAM-1 (vascular cell adhesion molecule 1, CD106) and E-selectin (CD62E). In this study, the effects of ibuprofen on IL-1 alpha and TNF alpha-induced expression of ICAM-1, VCAM-1 and E-selectin on cultured human umbilical vein EC (HUVEC) were analyzed. Exposure to IL-1 alpha or TNF alpha resulted in an increased expression of VCAM-1, ICAM-1, and E-selectin. Ibuprofen was identified as a potent inhibitor of IL-1 alpha and TNF alpha-induced surface expression of VCAM-1 and a less potent inhibitor of pyrogen-induced expression of ICAM-1, whereas no effect on E-selectin was found. The effects of ibuprofen on VCAM-1 expression were dose-dependent (IC50 [IL-1 alpha]: 0.5 mM; IC50 [TNF alpha]: 0.5 mM) and time-dependent with maximum responses observed after 18 h. Moreover, ibuprofen abrogated pyrogen-dependent adhesion of leukocytes to HUVEC. Ibuprofen also inhibited VCAM-1 mRNA expression in pyrogen activated EC. VCAM-1-downregulation on EC by ibuprofen may contribute to the anti-inflammatory actions of the drug.

Base Sequence↗

PubMed1996

Combined use of 111In-DTPA-D-Phe-1-octreotide (OCT) and 123I-vasoactive intestinal peptide (VIP) in the localization diagnosis of medullary thyroid carcinoma (MTC).

Although serum calcitonin and CEA are sensitive indicators for the presence of medullary thyroid carcinoma (MTC), the localization of tumor sites may be very difficult. In an approach to localize MTC lesions we performed comparative in vivo studies in 12 patients with primary MTC and in 4 patients with suspected recurrent MTC using 123I-VIP (150 MBq/1 microgram) and 111In-DTPA-D-Phe-1-octreotide (111In-OCT; 150 MBq/1 microgram). Despite elevated calcitonin values in all patients with suspected recurrent or metastatic lesions, both ultrasound and computed tomography (CT) were unable to localize a tumor site. 111In-OCT localized the primary tumor in the thyroid gland in 7 of 11 patients (63.5%). In 2 of 4 patients (50%) with suspected recurrent MTC, pathological uptake of 111In-OCT in the mediastinum or liver was demonstrable. In none of the 11 patients did 123I-VIP-receptor scanning indicate primary, recurrent, or metastatic tumor lesions. In vitro binding studies showed an absence of high-affinity VIP receptors in MTC tissue, whereas high-affinity 111In-OCT receptors were present in 4 of 6, and low-affinity 123I-VIP as well as 111In-OCT receptors were present in 6 of 6 MTC tissue samples. We conclude that somatostatin receptor scanning using 111In-OCT may visualize primary MTC, but it has only a low sensitivity in the detection of recurrent disease. The 123I-VIP-receptor scan is not helpful in the localization diagnosis of primary or recurrent MTC.

Adult↗

PubMed1996

123I-vasoactive intestinal peptide (VIP) receptor scanning: update of imaging results in patients with adenocarcinomas and endocrine tumors of the gastrointestinal tract.

Recent data suggest that functional receptors (R) for vasoactive intestinal peptide (VIP) are expressed on various tumor cells. The high-level expression of VIPR on tumor cells provided the basis for the successful use of 123I-labeled VIP for the in vivo localization of intestinal adenocarcinomas and endocrine tumors. We here report an update of our imaging results using 123I-VIP (150-200 MBg/1 microgram/patient) in 169 patients. In patients with pancreatic adenocarcinomas without liver metastases, the primary/recurrent tumor was visualized in 16 of 18 patients (89%) and liver metastases were imaged in 15 of 16 patients. In 11 of 12 patients with colorectal adenocarcinomas, the primary/recurrent tumor (92%) was imaged by 123I-VIP. Also, in 21 of 25 patients, liver metastases (84%); in 3 of 6 patients, lung metastases (50%); and in 4 of 5 patients, lymph-node metastases (80%) were imaged by 123I-VIP. In 10 of 10 patients with gastric adenocarcinomas, the primary/recurrent tumor; in 3 of 4 patients, liver metastases; and in 2 of 2 patients, lymph-node metastases were visualized by 123I-VIP. 123I-VIP localized primary intestinal carcinoid tumors in 15 of 17 patients (88%) and 8 of 10 primary insulinomas (80%). We conclude that the 123I-VIPR scintigraphy localizes intestinal adenocarcinomas and endocrine tumors as well as metastatic tumor sites.

Adenocarcinoma↗

PubMed1996

Effects of cyclosporin A and FK-506 on stem cell factor-induced histamine secretion and growth of human mast cells.

Stem cell factor (SCF) is a key regulator of human mast cells (MCs) and a potential mediator of allergy. In this study the effects of cyclosporin A (CSA) and FK-506, two potent immunosuppressive drugs, on SCF-dependent histamine release and growth of human MCs were analyzed. Preincubation of tissue MCs with CSA (3 micrograms/ml) resulted in inhibition of histamine release provoked by either recombinant human (rh) SCF (70.3% +/- 20.6% inhibition, p < 0.001) or anti-IgE (76.7% +/- 21.9%, p < 0.001) or by rhSCF+ anti-IgE (77.4% +/- 13.9%, p < 0.001). Almost the same inhibition was produced by FK-506 (rhSCF: 82.0% +/- 18.9% inhibition, p < 0.001; anti-IgE: 71.5% +/- 16.7%, p < 0.001; rhSCF+ anti-IgE: 70.0% +/- 7.3%, p < 0.001). The effects of CSA and FK-506 on SCF-dependent release of histamine were dose-dependent (IC50: CSA, 1 to 10 ng/ml; FK-506, 0.3 to 3 ng/ml). IC50 values about three to 10 times higher were found for MCs preincubated with rhSCF before anti-IgE activation, compared with anti-IgE or SCF alone. SCF-dependent differentiation of human MCs was analyzed in a long-term suspension culture system (n = 6). Unexpectedly, CSA and FK-506 were unable to suppress, but even enhanced SCF-dependent growth of MCs and formation of MC tryptase in long-term culture. Together, CSA and FK-506 inhibit SCF-dependent release of histamine from human MCs and even augment SCF-dependent growth of human MCs in long-term culture.

Cell Division↗

PubMed1996

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.

Adenocarcinoma↗

PubMed1995

Characterization of LDL and VLDL binding sites on human basophils and mast cells.

Recent data suggest that basophils and mast cells play a potential role in the processing and accumulation of plasma lipoproteins. This study investigated the interactions of 111In-low-density lipoprotein (LDL), 111In-acetyl-LDL, and 111In-very-low-density lipoprotein (VLDL) with purified primary human blood basophils, immortalized human basophils (KU812 cell line), and a human mast cell line, HMC-1. Binding sites for 111In-LDL resolved into curvilinear Scatchard plots indicating two classes of specific binding sites on primary basophils (Bmax1, 7404 sites/cell; Kd1, 1.9 nmol/L; Bmax2, 39,611 sites/cell; Kd2, 29 nmol/L), on KU812 cells (Bmax1, 8290 +/- 2690 sites/cell; Kd1, 2.4 +/- 0.6 nmol/L; Bmax2, 46,470 sites/cell; Kd2, 33.4 +/- 7.8 nmol/L), and on HMC-1 cells (Bmax1, 7840 +/- 360 sites/cell; Kd1, 1.8 +/- 0.8 nmol/L; Bmax2, 61,450 +/- 9900 sites/cell; Kd2, 28.4 +/- 9.4 nmol/L). On KU812 cells, binding of 111In-LDL was displaced by apolipoprotein (apo)-E-rich high-density lipoprotein (HDL) (IC50, 14 +/- 6 nmol/L), LDL (IC50, 29 +/- 11 nmol/L), VLDL (IC50, 55 +/- 21 nmol/L), HDL2 (IC50, 420 +/- 140 nmol/L), and heparin (IC50, 67 +/- 28 nmol/L), whereas no competition was produced by HDL, HDL3, or acetyl-LDL (IC50, > 1 mumol/L). Western blot analysis using the monoclonal antibody C7 confirmed the presence of the LDL receptor on human basophils and HMC-1 cells. 111In-acetyl-LDL binding sites (scavenger receptor) could be detected neither on human basophils nor on HMC-1 cells. 111In-VLDL bound to a single class of high-affinity binding sites on primary basophils (Bmax, 4320 sites/cell; Kd, 10 nmol/L), KU812 cells (Bmax, 4020 +/- 840 sites/cell; Kd, 8 +/- 3 nmol/L), and HMC-1 cells (Bmax, 6143 +/- 1866 sites/cell; Kd, 4 +/- 2 nmol/L). 111In-VLDL binding was displaced by VLDL > LDL > apoE-rich HDL but not by heparin (IC50 > 1 mmol/L). In the presence of prostaglandin E1, the number of 111In-LDL receptors increased by 150% (P < .05) in the high-affinity range and by 170% (P < .01) in the low-affinity range, whereas the number of 111In-VLDL binding sites remained unchanged. VLDL, LDL, HDL, and the subclasses HDL2 and HDL3 inhibited immunological histamine release by primary normal basophils (n = 3) and mast cells (n = 3). Our results provide evidence for the existence of LDL and VLDL binding sites on human basophils and HMC-1 mast cells. The exact biological and pathophysiological roles of these sites remain to be elucidated.

Basophils↗

PubMed1995

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.

Adenocarcinoma↗