High-Resolution Positron Emission Tomography of Human Ovarian Cancer in Nude Rats Using 124I-Labeled Monoclonal Antibodies

doi:10.1006/gyno.1993.1010

Gynecologic Oncology

Volume 48, Issue 1, January 1993, Pages 61-67

https://doi.org/10.1006/gyno.1993.1010 Get rights and content

Abstract

PET has inherently high resolution and excellent contrast imaging and accurately measures radioactivity concentrations in vivo. When combined with specific immunological targeting it might provide a highly specific and sensitive radioimmunoscintigraphic tool. To investigate this we injected ¹²⁴ I-labeled MAb MX35 or MAb MH99 monoclonal antibodies (doses 200-400 μCi) intravenously into nude rats bearing subcutaneous human ovarian cancer xenografts (SK-OV-7 and SK-OV-3 cell lines). A melanoma cell line (SK-MEL-30) was used as a control tumor. These murine monoclonal antibodies react with cell-surface antigens expressed by most ovarian cancer cells, including the ovarian cell lines used. Imaging was performed at 1-6 days using a high-resolution positron emission tomograph (PCR-I) with a spatial resolution of 4.5 mm. The slice thicknesses were 0.5 and 1.0 cm. Forty to seventy thousand coincident pulses were obtained per frame. The PET results were compared with those of autopsy and histology. Samples of blood, tumor, and normal tissues were obtained at various time points. PET calculation of isotope uptake ratios demonstrated specific localization of the antibodies in tumor, with ratios of tumor to normal tissue uptake as high as 6:1. Subcutaneous ovarian cancer nodules as small as 7 mm were identified with PET imaging. The results corresponded well with tissue sampling. Our findings suggest that PET imaging of tumors with ¹²⁴I-labeled monoclonal antibodies may be useful in human diagnostic and therapeutic applications in ovarian cancer as well as other diseases.

References (0)

Cited by (26)

Targeting NaPi2b in ovarian cancer
2023, Cancer Treatment Reviews
Citation Excerpt :
Preclinical and early clinical evidence suggest that NaPi2b is expressed in high-grade serous epithelial ovarian, fallopian tube, and primary peritoneal cancers, as well as in thyroid, breast, and nonsquamous non–small cell lung cancers, with limited expression in normal tissues [18–22]. The first evidence for high expression of NaPi2b in tumors came from studies in the 1980s and 1990s, which showed that the monoclonal antibody MX35 had high reactivity in ovarian tumors, although the identity of the antigen at the time was unknown [23–25]. In 2008, the epitope targeted by the MX35 antibody was discovered to be NaPi2b, which showed reactivity in 90 % of epithelial ovarian cancer cell lines [26].
Novel biomarkers are needed to direct new treatments for ovarian cancer, a disease for which the standard of care remains heavily focused on platinum-based chemotherapy. Despite the success of PARP inhibitors, treatment options are limited, particularly in the platinum-resistant setting. NaPi2b is a cell surface sodium-dependent phosphate transporter that regulates phosphate homeostasis under normal physiological conditions and is a lineage marker that is expressed in select cancers, including ovarian, lung, thyroid, and breast cancers, with limited expression in normal tissues. Based on its increased expression in ovarian tumors, NaPi2b is a promising candidate to be studied as a biomarker for treatment and patient selection in ovarian cancer. In preclinical studies, the use of antibodies against NaPi2b showed that this protein can be exploited for tumor mapping and therapeutic targeting. Emerging data from phase 1 and 2 clinical trials in ovarian cancer have suggested that NaPi2b can be successfully detected in patient biopsy samples using immunohistochemistry, and the NaPi2b-targeting antibody-drug conjugate under evaluation appeared to elicit therapeutic responses. The aim of this review is to examine literature supporting NaPi2b as a novel biomarker for potential treatment and patient selection in ovarian cancer and to discuss the critical next steps and future analyses necessary to drive the study of this biomarker and therapeutic targeting forward.
Radiolabelled proteins for positron emission tomography: Pros and cons of labelling methods
2010, Biochimica et Biophysica Acta - General Subjects
Dynamic biomedical research is currently yielding a wealth of information about disease-associated molecular alterations on cell surfaces and in the extracellular space. The ability to visualize and quantify these alterations in vivo could provide important diagnostic information and be used to guide individually-optimized therapy. Biotechnology can provide proteinaceous molecular probes with highly specific target recognitions. Suitably labelled, these may be used as tracers for radionuclide-based imaging of molecular disease signatures. If the labels are positron-emitting radionuclides, the superior resolution, sensitivity and quantification capability of positron emission tomography (PET) can be exploited.
This article discusses different approaches to labelling proteins with positron-emitting nuclides with suggestions made depending on the biological features of the tracers.
Factors such as matching biological and physical half-lives, availability of the nuclide, labelling yields, and influences of labelling on targeting properties (affinity, charge and lipophilicity, cellular processing and retention of catabolites) should be considered when selecting a labelling strategy for each proteinaceous tracer.
The labelling strategy used can make all the difference between success and failure in a tracer application. This review emphasises chemical, biological and pharmacological considerations in labelling proteins with positron-emitting radionuclides.
The Nude Rat
2006, The Laboratory Rat
The congenitally athymic nude rat (rnu/rnu) is a genetic mutant found in Rattus norvegicus characterized by a severe alteration in the cell-mediated branch of immunity (CMI). Altered cellular immune responses are owing to a lack of appropriate development and education of functional T-cell (thymus-derived) lymphocytes. The size and robustness of the nude rat and the absence of major endocrinological abnormalities make it an appropriate experimental model for a variety of immunological, surgical, infectious, transplant-related, and oncological procedures. Nude rats are uniquely capable of handling an increased tumor burden without overt distress, and the additional body size allows therapeutic intervention more easily than in a nude mouse. Therapeutic data for anti-neoplastic studies are presented in terms of (1) increased lifespan reflected by the relative median survival time of treated verses control groups (%treated/control); (2) cures; or (3) relative median times (in days) for the treated and control groups to grow tumors of a predetermined target size. The nude rat model has demonstrated value for many areas of biomedical research. From basic cellular function of immune cells to intricate interactions of tumors, treatment, and imaging modalities, the nude rat has provided a robust model of suitable size and appropriate response.
The Nude Rat
2005, The Laboratory Rat, Second Edition
The congenitally athymic nude rat (rnu/rnu) is a genetic mutant found in Rattus norvegicus characterized by a severe alteration in the cell-mediated branch of immunity (CMI). Altered cellular immune responses are owing to a lack of appropriate development and education of functional T-cell (thymus-derived) lymphocytes. The size and robustness of the nude rat and the absence of major endocrinological abnormalities make it an appropriate experimental model for a variety of immunological, surgical, infectious, transplant-related, and oncological procedures. Nude rats are uniquely capable of handling an increased tumor burden without overt distress, and the additional body size allows therapeutic intervention more easily than in a nude mouse. Therapeutic data for anti-neoplastic studies are presented in terms of (1) increased lifespan reflected by the relative median survival time of treated verses control groups (%treated/control); (2) cures; or (3) relative median times (in days) for the treated and control groups to grow tumors of a predetermined target size. The nude rat model has demonstrated value for many areas of biomedical research. From basic cellular function of immune cells to intricate interactions of tumors, treatment, and imaging modalities, the nude rat has provided a robust model of suitable size and appropriate response.
Comparison of animal models for the evaluation of radiolabeled androgens
2001, Nuclear Medicine and Biology
Biodistribution of two ¹⁸F-labeled androgens and an ¹²⁴I/¹²⁵I-labeled androgen were studied in five androgen receptor (prostate) animal models with or lacking sex hormone binding globulin (SHBG). As models for androgen-receptor positive ovarian cancer, xenografts of three human ovarian cancer cell lines were tested in SCID mice. SHBG in the prostate model systems significantly affects the metabolism, clearance, and distribution of the radiolabeled androgens in several tissues, but ovarian cancer animal models were disappointing.
Radiochemistry, production processes, labeling methods, and immunopet imaging pharmaceuticals of iodine-124
2021, Molecules

View all citing articles on Scopus

View full text

Regular ArticleHigh-Resolution Positron Emission Tomography of Human Ovarian Cancer in Nude Rats Using 124I-Labeled Monoclonal Antibodies

Abstract

Regular Article
High-Resolution Positron Emission Tomography of Human Ovarian Cancer in Nude Rats Using ¹²⁴I-Labeled Monoclonal Antibodies