Diagnostic efficacy and safety of 99mtc-labeled monoclonal antibody ior c5 in patients with colorectal and anal carcinomas: final report clinical trial phase I/II.

UNLABELLED: Monoclonal antibody (mAb) ior c5 is an IgG1, which recognizes a glycoprotein tumor specific antigen IOR C2 over expressed in the surface of colon and ovarian cancer cells. The aim of the present work was to evaluate the diagnostic efficacy of the 99mTc-labeled mAb ior c5 for the detection of colorectal tumors, its metastases and recurrences. METHODS: Eighty six patients with colorectal or anal cancer, mean age 57 +/- 13 yrs, were involved in a phase 1/11 multicentric, open clinical trial to assess the ability of Radioimmunoscintigraphy (RIS) with 99mTc- mAb ior c5 to detect those tumors. Seventy-four patients received 1 mg of c5 labeled with 1480-1850 MBq to determinate diagnosis efficacy and safety of murine mAb by intravenously (i.v.) bolus injection (group 1). In order to evaluate pharmacokinetic, bio distribution and dosimetry of this radiolabel molecule, 12 patients received 3 mg of labeled ior c5. Planar anterior and posterior images of the lesion sites and suspected metastases were acquired at 2, 4 and 18-24 hours after injection using a matrix size 128 x128 and 500 Kcounts per view. SPECT were scanned at 5 hr post-injection, using a 360' circular orbit with 64 images. HAMA response was measured in serum at 2, 4, 8 and 12 week post-administration. RESULTS: Labeling efficiency was (97.8 - 0.6) %. No adverse reactions or side effects were observed. Overall sensitivity, specificity, accuracy, positive and negative predictive values of the immunoscintigraphy were 95.80%, 100%, 96.51%, 100.0% and 82.35%, respectively. Unknown metastases were detected in 37 of 86 cases (43.02%). No HAMA response was found. CONCLUSIONS: Immunoscintigraphy with 99mTc-labeled mAb ior c5 could be a useful procedure for the diagnosis and follow-up of the patients with colorectal tumors, its metastasis and recurrences.

A multivalent recombinant antibody fragment specific for carcinoembryonic antigen.

In the present paper we report the development of a bivalent scFv (single-chain Fv) antibody fragment, starting from a mouse mAb (monoclonal antibody) specific for CEA (carcinoembryonic antigen) that has received approval for in vivo radioimmunodiagnosis in humans. The diabody is well expressed in Escherichia coli, is easily purified by a combination of immobilized metal ion affinity chromatography and gel filtration and exhibits high affinity and specificity for CEA, comparable with those of the original mAb. Biodistribution experiments in athymic nude mice transplanted with human CEA+ cancer cells showed that the 125I-labelled diabody preferentially localizes in the tumour tissue and that retention is still high 48 h after injection. The diabody can be advantageous for some in vivo tumour targeting applications, due to the faster clearance derived from its smaller molecular mass.

Clinical evidences of GM3 (NeuGc) ganglioside expression in human breast cancer using the 14F7 monoclonal antibody labelled with (99m)Tc.

The relevance of certain gangliosides in tumour growth and metastatic dissemination has been well documented, reasons for considering these molecules as potential targets for cancer immunotherapy and diagnosis. GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues according to immunohistochemical studies, using either polyclonal or monoclonal antibodies. But both immunohistochemical and biochemical methods have strongly suggested its over-expression in human breast tumours. Nevertheless, the lack of a direct evidence of this antigenic display in human breast cancer has kept the subject controversial. For the first time, we described herein the "in vivo" detection of GM3(NeuGc) ganglioside in human breast primary tumours using a radioimmunoscintigraphic technique with 14F7, a highly specific anti-GM3(NeuGc) ganglioside monoclonal antibody, labelled with (99m)Tc. In an open, prospective Phase I/II clinical trial, including women diagnosed in stage II breast cancer, the 14F7 monoclonal antibody accumulation in tumours at doses of 0.3 (n=5), 1 (n=5) and 3 mg (n=4) was evaluated. Noteworthy, the immunoscintigraphic study showed antibody accumulation in 100% of patients' tumours for the 1 mg dose group. In turn, the radioimmunoconjugate injected at doses of 0.3 mg or 3 mg of the antibody, was uptaken by 60 and 33.3% of breast tumours, respectively. "In vivo" immune recognition of GM3(NeuGc) in breast tumours reinforces the value of this peculiar target for cancer immunotherapy.

Dosimetria interna de radioinmunoterapia: consideraciones generales / Radioimmunotherapy internal dosimetry: general considerations

La Radioinmunoterapia ha atraído rápidamente el interés como modalidad potencial en el tratamiento del cáncer. Este presente trabajo revisa varios aspectos dosimétricos que involucran la efectividad de la técnica, así como, los procedimientos empleados en la obtención de la información dosimétrica, el tipo de radionucleido seleccionado, las limitaciones y posibilidades de los métodos de estimación dosimétrica; y proporciona un estudio detallado sobre los modelos radiobiológicos que con potencialidad pueden ser utilizados en la prescripción de la dosis en un sistema de planificación que permita establecer una relación dosis/respuesta del tratamiento(AU)

Radioimmunotherapy has a growing interest as a new potential modality for cancer treatment. In this paper several aspects are discussed: effectiveness of radioimmunotherapy, the procedures to get dosimetric information, the appropriate radionucleide and the possibilities and limitations that dosimetric estimation methods offer. A detailed study about radiobiological models which can be used for dose prescription is also presented(AU)

Dosimetria interna de radioinmunoterapia: consideraciones generales / Radioimmunotherapy internal dosimetry: general considerations

La Radioinmunoterapia ha atraído rápidamente el interés como modalidad potencial en el tratamiento del cáncer. Este presente trabajo revisa varios aspectos dosimétricos que involucran la efectividad de la técnica, así como, los procedimientos empleados en la obtención de la información dosimétrica, el tipo de radionucleido seleccionado, las limitaciones y posibilidades de los métodos de estimación dosimétrica; y proporciona un estudio detallado sobre los modelos radiobiológicos que con potencialidad pueden ser utilizados en la prescripción de la dosis en un sistema de planificación que permita establecer una relación dosis/respuesta del tratamiento