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Biomedical subjects

C S Marcus

Publications and source records attributed to C S Marcus.

At least 19 recordsLinked to original sources

99mTc labeled VIP analog: evaluation for imaging colorectal cancer.

Early and reliable diagnosis of colorectal cancer continues to be demanding and challenging. Colorectal cancer cells express Vasoactive Intestinal Peptide (VIP) receptors in high density. We have prepared a VIP analog (TP3654), labeled it with (99m)Tc, and evaluated it in experimental animals as an agent for imaging colorectal cancer. The tissue distribution of (99m)Tc-TP3654 has been compared with that of (111)In-DTPA-Octreotide and (99m)Tc-anti-CEA scan in nude mice bearing human colorectal cancer LS174T. Finally, pharmacokinetic and tissue distribution studies of (99m)Tc-TP3654 have been performed in four normal human volunteers. Data suggest that (99m)Tc-TP3654 can be prepared efficiently without loss of its receptor specificity and biological activity. Although the 24 hr tumor uptake of (99m)Tc-TP3654 in the animal model used was modest (0.21 +/- 0.07% I.D./g), the tissue distribution profile was more favorable than that of (111)In-DTPA-Octreotide or (99m)Tc-anti-CEA scan. Human studies indicated that (99m)Tc-TP3654 had no adverse effect in any subject. Within 24 hours, approximately 70% of the injected dose cleared through the kidneys, and approximately 20% through the hepatobiliary system. In these non-fasting volunteers hepatobiliary clearance was slow and in cancer patients tumor uptake was rapid. Data suggest that (99m)Tc-TP3654 is a promising agent for imaging colorectal cancer.

Colorectal Neoplasms↗

Imaging infection with LeuTech.

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.

Adult↗

Imaging tumors in humans with Tc-99m-VIP.

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.

Adenocarcinoma↗

99mTc-labeled vasoactive intestinal peptide analog for rapid localization of tumors in humans.

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.

Adult↗

Augmentation of leukocyte count with G-CSF in a patient with neutropenia before In-111 WBC scintigraphy.

Neutropenia with persistent fevers and a wound infection developed in a patient with AIDS after an uncomplicated hysterectomy. After a single dose of G-CSF (granulocyte-colony stimulating factor), the WBC count transiently recovered, and an In-111 labeled WBC scan was successfully performed to exclude an intra-abdominal source of infection and to implicate the superficial wound as a source of her fevers. The patient underwent wound debridement the next day and made an uneventful recovery. This article describes a potential new role for G-CSF, namely enhancement of the WBC count in patients with neutropenia who are referred for In-111 WBC imaging to improve diagnostic yield.

Acquired Immunodeficiency Syndrome↗

Imaging inflammatory diseases with neutrophil-specific technetium-99m-labeled monoclonal antibody anti-SSEA-1.

UNLABELLED: Imaging inflammatory diseases with a 99mTc-labeled neutrophil-specific agent that can be injected directly intravenously continues to be a challenge. METHODS: The antibody, anti-SSEA-1, chosen from studies of 10 neutrophil-specific MAbs, recognizes CD-15 antigens (5.1 x 10(5)/human PMN) with a high association constant (kd = 10(-11) M). One hundred micrograms of MAb labeled with 10-20 mCi 99mTc either by a direct or DTPA conjugation method were injected intravenously into 12 patients (9 men, 3 women, aged 19-48 yr) with clinical evidence of ongoing inflammatory processes. Vital signs of all patients were recorded before and up to 3 hr following administration of the MAb. HAMA was determined in two patients. Anterior and posterior spot views and whole-body images were obtained. All patients except one underwent biopsy, US or CT examinations and/or surgical procedures. Blood samples collected from five patients were analyzed. In nine patients, quantitative organ distribution was determined and radiation dosimetry was calculated. RESULTS: Labeling yields were 94.8% +/- 1.4% and 95.8% +/- 3.5%, respectively. All patients had unequivocally positive images within 3 hr of the MAb injection. Eleven of these were confirmed by other modalities. One patient recovered on antibiotics and was sent home without surgery or other procedures. The lack of radioactivity in the thyroid or gastrointestinal tract indicated that the in vivo stability of the agent was excellent. At 3 hr postinjection, bladder activity in six patients was 1.3% +/- 0.4% of the administered dose. At this time, splenic uptake (7.7% +/- 1.0% ad. dose) and red marrow uptake (14 +/- 1.8%) were lower than those of 111In-WBC. At 49.0% +/- 3.2% administrated dose, liver uptake was at the upper limit with 111In-WBC uptake. Renal uptake was only 2.4% +/- 0.03% administered dose. At 2 hr postinjection, 14% to 51% of the radioactivity was associated with PMN. Radioactivity with lymphocytes was 0.7% to 10.9%, 1.2% to 4.3% with platelets and 1.1% to 2.4% with RBC. No HAMA were detectable in either patient, and no adverse reaction was detectable in any patient. CONCLUSION: Results are highly encouaging and have prompted us to prepare a kit for instant preparation and to initiate clinical trials.

Abscess↗

Tc-99m sestamibi and In-111 pentetreotide uptake in metastatic papillary thyroid carcinoma.

Approximately 25% of metastatic and recurrent differentiated (papillary and follicular) thyroid carcinoma do not concentrate 1-131 Nal. In such cases, diagnosis can be attempted with other radiopharmaceuticals. The authors present a case of recurrent papillary thyroid carcinoma that was well visualized with Tc-99m sestamibi and In-111 pentetreotide; but only poorly visualized by I-131 Nal.

Aged↗

The extension of 4 degrees C storage time of frozen-thawed red cells.

Blood was drawn from volunteer donors and frozen using the high glycerin, mechanical freezing procedure accepted by the United States Navy. Subsequently, the units of blood were thawed and washed. Various anticoagulants were added, and the red cells were stored in a refrigerator at 4 degrees C for periods of up to 28 days. Chemical analyses were performed periodically. These showed that the addition of the anticoagulants ACD, CPD and CPDA-1 caused the red cells to be preserved better than the currently accepted 0.9-percent NaCl, 0.2-percent glucose solution. In vivo 51Cr viability studies performed on blood stored with CPDA-1 for 14 days showed a 24-hour viability of 78.8 +/- 8.4 percent. In a subsequent study, the blood was stored for 21 days prior to freezing and then was rejuvenated and frozen. The cells were thawed, washed, and stored at 4 degrees C with CPDA-1 for an additional 14 days. The 24-hour viability of these cells was determined to be 74.0 +/- 5.1 percent. These findings show that the postthaw storage time of red cells can be increased greatly over the now-accepted 24 hours, if bacterial sterility can be assured.

Blood Preservation↗

Modified polytetrafluoroethylene: indium 111-labeled platelet deposition on carbon-lined and high-porosity polytetrafluoroethylene grafts.

Platelet accumulation on carbon-lined (CL) and high-porosity (HP) polytetrafluoroethylene (PTFE) grafts was investigated in vivo. In experiment 1, 20 CL grafts and 20 control PTFE grafts, each 5 cm in length and 4 mm in diameter, were interposed into both carotid and femoral arteries of 10 dogs. In experiment 2, 12 HP grafts (90 microns mean internodal distance) and 12 control PTFE grafts were implanted in six dogs. Indium 111-labeled platelets were injected intravenously and the grafts were retrieved 48 hours later. Radioactivity of the grafts and a control segment of the carotid artery was counted. A graft platelet accumulation index (GPAI) was calculated as the ratio of emission from the graft compared to that from the control segment. The GPAI of the CL graft was significantly less than the GPAI of the control graft in both the carotid (control 29.7 +/- 5.46, CL 22.3 +/- 6.55; n = 9 [p < 0.05]) and the femoral arteries (control 30.7 +/- 9.65, CL 22.0 +/- 6.59; n = 9 [p < 0.05]). There was no significant difference in GPAI between the control and HP grafts in the carotid arteries (control 30.6 +/- 11.8, HP 31.5 +/- 9.71; n = 6) and in the femoral arteries (control 31.5 +/- 7.88, HP 34.0 +/- 4.97; n = 6). Carbon lining decreases platelet accumulation on PTFE grafts in the early postoperative period, and HP grafts do not exhibit increased platelet uptake.

Animals↗

Radiation dosimetry for the adult female and fetus from iodine-131 administration in hyperthyroidism.

Through a study of the iodine kinetics of 127 patients, we have developed radiation dose estimates to major organs and the fetus for patients with varying degrees of hyperthyroidism. We observed a negative correlation between maximum thyroid uptake and biologic half-time of iodine in the thyroid and used this correlation to predict the biologic half-time at fixed values of maximum thyroid uptake. Dose estimates to the bladder, gonads, marrow, thyroid, uterus, and whole body were estimated for maximum thyroid uptakes from 20% to 100%. Bladder dose varied from 0.6 to 1.0 mGy/MBq and dose to the uterus varied from 0.036 to 0.063 mGy/MBq under different model assumptions. Dose estimates to the fetus and fetal thyroid were approximated at all stages of pregnancy. Average fetal dose was a maximum between 0 and 2 mo of pregnancy, with the maximum ranging from 0.048 mGy/MBq to 0.083 mGy/MBq, depending on model assumptions. Some radiation risks for irradiation of the fetus and the fetal thyroid are discussed.

Adult↗

Evaluation of women with possible appendicitis using technetium-99m leukocyte scan.

The authors evaluated the use of technetium-99m albumin colloid white blood cell (TAC-WBC) scan in women with possible appendicitis. One hundred and nine women underwent 110 TAC-WBC scans. One woman had a second scan on a separate admission and was considered two individual patients in the analysis. Twenty-six women had appendicitis, 10 of whom had a perforated appendix at surgery. The TAC-WBC scan was indeterminate (abnormal but nondiagnostic for appendicitis) in 52 women (47%), nine of whom had appendicitis. Fifty-eight scans were read as positive or negative for appendiceal pathology. There were 16 true positives, 5 false positives, 36 true negatives, and 1 false negative. The predictive value of a positive scan was 76%, and the predictive value of a negative scan was 97%. The TAC-WBC scan was positive in 62% of patients with appendicitis and negative in 43% of the patients without appendicitis resulting in an overall accuracy of 47% in the 109 women. The main value of TAC-WBC scan in women with possible appendicitis is its high negative predictive value and the main problem with the TAC-WBC scan is its high indeterminate rate.

Abdominal Pain↗