Investigation of 3'-debenzoyl-3'-(3-([¹²4I]-iodobenzoyl))paclitaxel analog as a radio-tracer to study multidrug resistance in vivo.

A study was carried out to identify a suitable radioactive paclitaxel analog and to use it to investigate tumor multidrug resistance in vivo. 3'-Debenzoyl-3'-(3-([(124)I]-iodobenzoyl))paclitaxel was prepared by aromatic iodination of 3'-debenzoyl-3'-(3-trimethylstannylbenzoyl)paclitaxel. Uptake of the labeled paclitaxel analog in nude mice bearing tumor with the paclitaxel sensitive cancer cell lines MCF7 and MDA-435/LCC6(WT), and multidrug resistant cell lines NCI/ADR-RES and MDA-435/LCC6(MDR), was studied. There was no difference in drug level between the sensitive and resistant MDA-435/LCC6 tumors at 6h post-injection. However, at 6h, there was a significant increase in drug level for the MCF7 tumor as compared with the NCI/ADR-RES tumor, presumably due to increased drug retention. At 24h, drug uptake/retention was significantly higher in both sensitive tumor cell lines as compared to their drug resistant counterparts. Pretreatment of mice with MDR transport modulators, Cyclosporine or tRA 96029, did not increase the level of labeled paclitaxel analog in the drug resistant MDA-435/LCC6(MDR) tumor. On the other hand, at 24h Cyclosporine apparently increased analog level in the drug sensitive MDA-435/LCC6(WT) tumor, aiding drug imaging studies.

Optimization of 124I production via 124Te(p,n)124I reaction.

(124)I was produced, via (124)Te(p,n)(124)I reaction, in greater than 3.7GBq (100 mCi, EOB) amount by bombarding (124)TeO(2) targets at 24 microA current for about 8h. This was achieved by keeping the target at 37 degrees relative to the beam during irradiation, by sweeping the beam across the target and by keeping the incident energy of the proton at 14.1MeV. The time-averaged yield of our 8h run was 21.1 MBq/microAh (0.57 mCi/microAh), which was 90% of the theoretical yield calculated using thick target yield data obtained from the reported excitation function for the reaction. At the end of bombardment, the level of (125)I and (126)I impurities, co-produced with (124)I, were 0.03% and 0.007%, respectively.

Clinical and technical considerations for imaging colorectal cancers with technetium-99m-labeled antiCEA Fab' fragment.

OBJECTIVE: Colorectal cancer is the third most common cancer, after lung and breast cancers. Approximately 133,500 Americans develop colorectal cancer annually and approximately 54,900 die of the disease. As many as 600,000 individuals in the US are under care after surgery for colorectal cancer. After reading this article, the nuclear medicine technologist will be able to: (a) describe the role of Arcitumomab in evaluating and managing patients with recurrent colorectal carcinoma metastasizing to the liver; (b) discuss the clinical use of CEA-Scan (Immunomedics, Inc., Morris Plains, NJ) and its overall imaging performance characteristics and sensitivity related to specific anatomical sites compared to conventional diagnostic modalities; (c) describe radiopharmaceutical preparation and quality control; (d) identify the pertinent patient history before starting the test; and (e) explain the imaging procedure, processing and display of data to optimize study interpretation.

Breast cancer imaging with radiolabeled antibodies.

Over the past 2 decades, numerous anticancer antibodies against different molecular targets and labeled with different gamma-emitting radionuclides have been studied in human tumor xenografts and in clinical trials. In breast cancer, these molecular targets have included principally tumor-associated antigens, such as carcinoembryonic antigen (CEA) and the polymorphic epithelial mucin antigen, MUC1, and more recently the growth factor receptors, EGF-R and HER-2/neu. No antibody-based agent has yet been approved for clinical use in the diagnosis of mammary carcinoma, because few trials have addressed the issue of clinical use of these imaging agents in the management of breast cancer patients. Recently, the CEA antibody Fab' fragment approved for colorectal cancer detection, Arcitumomab (CEA-Scan, [Immunomedics, Morris Plains, NJ]), has been found to image both palpable and nonpalpable breast lesions that were suspicious on screening mammograms. Results to date indicate that Arcitumomab can complement mammography by providing a high specificity and positive predictive value, thus indicating when a patient with an abnormal mammogram may proceed directly to definitive surgery without an intermediate diagnostic biopsy. Breast cancer immunoscintigraphy holds promise for advancing toward immunoPET, which should combine the specificity of antibodies with the high sensitivity and resolution of PET. It is also the foundation of breast cancer radioimmunotherapy with humanized antibodies against CEA and MUC1, as well as other immunotherapy strategies.

Development of oncology protocol using fluorine-18-FDG: one center's experience.

The major types of cancer studied at the authors' facility were colorectal (107 patients), head and neck (122 patients), gastric/esophageal (57 patients), lung (59 patients) and lymphoma (26 patients). This article presents guidelines and techniques for obtaining optimal PET studies. The authors devised these guidelines through trial and error and hope that by sharing them other facilities can avoid unnecessary mistakes and achieve better quality studies more efficiently.

Antibody imaging in breast cancer.

Radiolabeled antibodies have been studied by several investigators for their ability to detect and stage breast cancers. Studies with Technetium-99m labeled anti-CEA monoclonal antibodies, Iodine-123, Indium111 labeled anti-mucin antibodies such as HFMG, B72.3, anti-TF and Iodine-125 labeled B72-3 have demonstrated the ability of radioimmunoscintigraphy in detecting over 80% of breast cancer lesions, but lower sensitivity and specificity for accurate staging of the axillae. Non-specific localization of radiolabeled monoclonal antibodies in tumor negative nodes even following lymphoscintigraphy appear to be the major factor limiting the widespread clinical application of radioimmunoscintigraphy in staging newly diagnosed breast cancer patients. Preliminary studies with Tc-99m labeled CEA-Scan appear to indicate a useful role of this agent in distinguishing between benign and malignant breast lesions in patients with indeterminate mammographic findings.

Superiority of SPET to planar imaging in the detection of colorectal carcinomas with 111In monoclonal antibodies.

The aim of this study was to assess the contribution of single photon emission tomography (SPET) to planar imaging of colorectal carcinoma in patients being evaluated with 111In-labelled monoclonal antibodies CYT-103 (OncoScint CR/OV) or IVP ZCE 025. Planar and SPET scans from 110 colorectal carcinoma patients were scored individually as follows: 1=negative, 2=equivocal, 3=positive. The planar and SPET images identified 67 and 93 of 113 documented lesions, respectively. The planar and SPET findings were concordant in 55 patients. SPET converted planar findings from 1 to 3 in 11 patients and from 2 to 3 in 21 patients. SPET provided a better definition of the extent of the tumour in 21 patients. Both imaging tests were true-negative in five patients, and failed to detect tumours in six patients. We strongly recommended SPET in all patients undergoing immunoscintigraphy, since it identified tumours missed on planar scans in 35% of patients and provided additional information regarding tumour burden in 23% of patients.

Radiolabeled monoclonal antibody imaging (immunoscintigraphy) of colorectal cancers: current status and future perspectives.

Over the past two decades, the role of radiolabeled monoclonal antibodies has been steadily growing in clinical practice, particularly for staging and locating a variety of neoplasms. This is due largely to the availability of these products in pharmaceutical quantities as well as the relatively low incidence of adverse reactions following the intravenous administration of antibodies to patients. One particular area of oncology where radiolabeled monoclonal antibodies are most likely to play an extremely important clinical role is in the evaluation of patients with colon and rectal carcinomas. In this report, we review the current utilization of tumor-associated monoclonal antibodies in the preoperative as well as postoperative screening of patients with colorectal carcinoma.

Indium-111 white blood cell scan for infectious complications of polycystic renal disease.

This case report describes the localization of a unilateral renal abscess with [111In]oxine-labeled autologous leukocyte scanning in a febrile patient with polycystic renal disease, after other noninvasive imaging procedures failed to identify a source of infection. In polycystic renal disease, leukocyte scans have advantages over standard diagnostic modalities and are very helpful in planning appropriate therapy.