ABSTRACT
LeuTech is a 99Tcm labelled, anti-CD15, IgM, murine monoclonal antibody shown to have high affinity (Kd = 10(-11) M) for CD15 receptors (5.1 x 10(5)/cell) expressed on human neutrophils. LeuTech was injected directly, intravenously, and its efficacy in imaging infection in 46 consecutive patients was determined. Human anti-mouse antibody (HAMA) response was examined in 30 normal volunteers using a standard LeuTech dose reconstituted with decayed 99Tcm solution. There were 38 true positive, six true negative, and two false negative scans. Of the 38 positive images, 33 (92%) were positive within 10 min after injection of LeuTech. LeuTech accuracy in this group of patients was 96%, sensitivity 95%, specificity 100%, positive predictive value (PPV) 100%, and negative predictive value (NPV) 75%. No elevation of the HAMA titre was observed in any of the 30 normal volunteers and no adverse reaction was noted in any patient. LeuTech is a highly promising agent for rapid imaging of infectious foci.
Subject(s)
Antibodies, Monoclonal , Infections/diagnostic imaging , Radiopharmaceuticals , Adult , Animals , Appendicitis/diagnostic imaging , Bone Diseases/diagnostic imaging , False Negative Reactions , Female , Humans , Lewis X Antigen/immunology , Lung Diseases/diagnostic imaging , Male , Mice , Middle Aged , Predictive Value of Tests , Reference Values , Reproducibility of Results , Sensitivity and Specificity , Tomography, Emission-Computed, Single-PhotonABSTRACT
In recent years, imaging tumors with receptor-specific biomolecules has been the focus of increasing interest. Vasoactive intestinal peptide (VIP) has a high affinity for specific receptors that are expressed in high density on a large number of malignant tumors. VIP was modified (TP 3654) without compromising its biologic activity and labeled with 99mTc. Pharmacokinetics and feasibility studies were performed in 3 healthy volunteers and 11 patients with a history of cancer. Imaging was performed for up to 2 h after injection. Within 24 h after injection of 99mTc-TP 3654 (370-555 MBq/5 microg), approximately 70% of the tracer cleared through the kidneys and 20% through the liver. Blood clearance was rapid. No adverse reaction was noted in any subject. All known tumors were clearly delineated within 20 min. Findings were compared with the results of 99mTc-methoxyisobutyl isonitrile, CT, MRI, or histology. There was concordance in 9 patients. In the other 2 patients, only the VIP scan was positive for tumors known to express VIP receptors. The early results of imaging tumors with 99mTc-VIP are promising and warrant further study.
Subject(s)
Neoplasms/diagnostic imaging , Oligopeptides , Radiopharmaceuticals , Technetium , Vasoactive Intestinal Peptide , Adult , Feasibility Studies , Female , Humans , Isotope Labeling , Male , Middle Aged , Oligopeptides/pharmacokinetics , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Time Factors , Vasoactive Intestinal Peptide/pharmacokineticsABSTRACT
Vasoactive intestinal peptide (VIP) was modified at the C terminus with a spacer and four amino acids to serve as a chelating moiety. The modified peptide, TP 3654, was labeled with Tc-99m and evaluated in normal volunteers, as well as in patients with a history of cancer. Renal clearance (67%) was the primary route of excretion, with approximately 20% of the radioactivity clearing through the hepatobiliary system. No adverse reaction was noted in any of the subjects and all, except one small, of the known lesions as seen by CT, MRI, Tc-99m-MIBI, or mammography were correctly identified within a few minutes of an i.v. injection of approximately 10 mCi of Tc-99m-TP 3654 (specific activity 11.3 x 10(3) Ci/m mol). The scans were in concordance in nine patients. In the remaining two, one with a visible mass in the neck from high grade spindle cell sarcoma and the other with a palpable mass in a breast from ductal epithelial hyperplasia, were localized only with Tc-99m-TP 3654, but not with Tc-99m-MIBI. Both malignancies are known to express VIP receptors. The VIP analog promises to be a nontoxic and reliable agent for imaging cancers in humans that express VIP receptors.
