Radiolabelled Monoclonal Antibodies Research Articles

The Management of Children with Pre-School Medulloblastoma – A Review of Four Decades of Multi-Disciplinary and Multi-Institutional Collaboration.

Background: The management and consequent survival and quality of survival for young children with medulloblastoma have undergone substantial improvement over the last four decades. While many of these changes reflect improvements in pediatric neurosurgical, neuro- imaging and radiation oncologic technology and training, as well as in supportive care experience and expertise, this review will focus particularly upon improvements in chemotherapeutic approaches. Methods: This review focuses only upon prospective clinical trials conducted in young children with newly-diagnosed medulloblastoma since the 1980s. The upper age limits for these trials varied from under three to up to six years of age at diagnosis. Results: Certain but not all trials endeavoring to improve outcomes for young children with now- recognized pathological and molecular low-risk characteristics, specifically the Sonic Hedgehog (SHH) sub-type, representing some 50-60% of young children with medulloblastoma, have reaped substantial gains in event-free and overall survival, irradiation-free survival as well as neuropsychological outcomes. Those successful trials utilized either induction including intravenous high-dose methotrexate and intraventricular (intra-Ommaya) methotrexate without consolidation by marrow-ablative chemotherapy with autologous hematopoietic progenitor cell rescue (AuHPCR), or induction with or without intravenous high-dose methotrexate (but not intra-ventricular methotrexate) followed by consolidation with marrow-ablative chemotherapy with AuHPCR. These two approaches have consistently produced superior outcomes compared with other trials. For children with molecularly-characterized Groups 3 or 4 medulloblastoma, representing those at high-risk of relapse, some modest improvements have been made over the years, but much room for improvement remains, especially for those presenting with the highest- risk molecular characteristics (CMYC-amplified Group 3 medulloblastoma) as well as for children with metastatic disease at initial diagnosis. Conclusions: Substantial gains in improving outcomes for young children with medulloblastoma have been achieved with acceptable short- and long-term morbidities of treatment. However, the inclusion of intra-ventricular therapies (conventional chemotherapeutic, radio-labeled monoclonal antibody or adaptive cellular immunotherapeutic approaches) as well as the identification of targeted systemic therapies (biological and/or immunological) and their incorporation into prospective multi-center clinical trials, must be investigated prospectively if we are to improve outcomes for those children at high-risk for relapse, even with the inclusion of refined irradiation therapeutic approaches.

Radioimmune Imaging of α4β7 Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease

Imaging using radiolabelled monoclonal antibodies can provide, non-invasively, molecular information which allows for the planning of the best treatment and for monitoring the therapeutic response in cancer, as well as in chronic inflammatory diseases. In the present study, our main goal was to evaluate if a pre-therapy scan with radiolabelled anti-α4β7 integrin or radiolabelled anti-TNFα mAb could predict therapeutic outcome with unlabelled anti-α4β7 integrin or anti-TNFα mAb. To this aim, we developed two radiopharmaceuticals to study the expression of therapeutic targets for inflammatory bowel diseases (IBD), to be used for therapy decision making. Both anti-α4β7 integrin and anti-TNFα mAbs were successfully radiolabelled with technetium-99m with high labelling efficiency and stability. Dextran sulfate sodium (DSS)-induced colitis was used as a model for murine IBD and the bowel uptake of radiolabelled mAbs was evaluated ex vivo and in vivo by planar and SPECT/CT images. These studies allowed us to define best imaging strategy and to validate the specificity of mAb binding in vivo to their targets. Bowel uptake in four different regions was compared to immunohistochemistry (IHC) score (partial and global). Then, to evaluate the biomarker expression prior to therapy administration, in initial IBD, another group of DSS-treated mice was injected with radiolabelled mAb on day 2 of DSS administration (to quantify the presence of the target in the bowel) and then injected with a single therapeutic dose of unlabelled anti-α4β7 integrin or anti-TNFα mAb. Good correlation was demonstrated between bowel uptake of radiolabelled mAb and immunohistochemistry (IHC) score, both in vivo and ex vivo. Mice treated with unlabelled α4β7 integrin and anti-TNFα showed an inverse correlation between the bowel uptake of radiolabelled mAb and the histological score after therapy, proving that only mice with high α4β7 integrin or TNFα expression will benefit of therapy with unlabelled mAb.

Clinical Applications of Immuno-PET in Lymphoma: A Systematic Review

Simple SummaryA systematic review of the published literature was performed to assess current clinicalapplications of immuno-PET in patients diagnosed with any histological type of lymphoma. The initial search yielded 1407 articles from PubMed/Medline and Scopus databases, but only 2 articles were found to comply with the inclusion criteria and 2 more were found during the cross-reference check. All four articles were deemed of sufficient methodological quality according to the QUADAS-2 assessment and were included in the review. Among the four included articles, three described the use of 89Zr-labelled antibodies targeting CD20+ relapsed/refractory B-cell lymphomas and one concerned the use of 68Ga-labelled mAb targeting CXCR4 in patients with non-Hodgkin lymphomas. Very limited literature data are currently available on the use of iPET in patients with lymphoma. However, iPET may represent a useful tool to non-invasively visualize the heterogeneous individual immunological environment, thus potentially guiding treatment-planning in lymphoma patients, and hence deserves further exploitation.Objective: Immuno-positron emission tomography (iPET) combines the sensitivity of the PET imaging technique and the targeting specificity of radio-labelled monoclonal antibodies (mAb). Its first clinical applications in humans were described in the late 1990s, and several pathologies have benefitted from this molecular imaging modality since then. Our scope was to assess current clinical applications of immuno-PET in patients with lymphoma. Therefore, a systematic review of the published literature was performed. Methods: PubMed/Medline and Scopus databases were independently searched by two nuclear medicine physicians, to identify studies describing the clinical use of immuno-PET in patients with lymphoma. Methodological quality of the included articles was assessed by using the Quality Assessment of Diagnostic Accuracy Studies criteria. The studies were then analyzed concerning the molecular target of interest. Results: The initial search yielded 1407 articles. After elimination of duplicates, 1339 titles/abstracts were evaluated. Only two articles were found to comply with the inclusion criteria and two more were found during the cross-reference check. Among the four included articles, three described the use of 89Zr-labelled antibodies targeting CD20+ relapsed/refractory B-cell lymphomas and one concerned the use of 68Ga-labelled mAb targeting CXCR4 in patients with non-Hodgkin lymphomas. Conclusions: Very limited literature data are currently available on the clinical use of iPET in patients with lymphoma. This technique is encountering obstacles in its wider use, possibly because of the need of specific facilities, unfavorable dosimetry, and unclear correlation of immuno-tracer biodistribution with patients’ clinical and tumors’ molecular characteristics. However, iPET may represent a useful tool to non-invasively visualize the heterogenous individual immunological environment, thus potentially guiding treatment-planning in lymphoma patients, and hence deserves further exploitation.

Adjuvant 131I-metuximab for hepatocellular carcinoma after liver resection: a randomised, controlled, multicentre, open-label, phase 2 trial

Effective adjuvant treatment after hepatectomy for hepatocellular carcinoma (HCC) is an important area of research. Radioactive iodine (131I)-labelled metuximab is a radiolabelled monoclonal antibody against the CD147 (also known as basigin or HAb18G) antigen that is expressed in HCC. We aimed to examine the role of 131I-metuximab as an adjuvant therapy after HCC resection. This randomised, controlled, multicentre, open-label, phase 2 trial was done at five medical centres in China. Patients aged 18-75 years who underwent curative-intent resection of histologically confirmed HCC expressing CD147 were randomly assigned (1:1) by a computer-generated random sequence, stratified by centre, to receive either adjuvant transarterial injection of one dose of 27·75 MBq/kg 131I-metuximab 4-6 weeks after the hepatectomy (treatment group) or no adjuvant treatment (control group). Patients and physicians were not masked to the study groups. The primary outcome was 5-year recurrence-free survival (RFS) in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT00819650. Between April 1, 2009, and Nov 30, 2012, 485 patients were screened for eligibility. 329 (68%) of these patients were excluded and 156 (32%) were randomly assigned to receive either 131I-metuximab (n=78) or no adjuvant treatment (n=78). The median follow-up was 55·9 months (IQR 18·6-79·4). In the intention-to-treat population, the 5-year RFS was 43·4% (95% CI 33·6-55·9) in the 131I-metuximab group and 21·7% (14·2-33·1) in the control group (hazard ratio 0·49 [95% CI 0·34-0·72]; Z=2·96, p=0·0031). 131I-metuximab-associated adverse events occurred within the first 4 weeks in 34 (45%) of 76 patients, seven (21%) of whom had grade 3 or 4 adverse events. These adverse events were all resolved with appropriate treatment within 2 weeks of being identified. Adjuvant 131I-metuximab treatment significantly improved the 5-year RFS of patients after hepatectomy for HCC tumours expressing CD147. This treatment was well tolerated by patients. State Key Project on Infectious Diseases of China.

Targeted Therapy of Osteosarcoma with Radio-labelled Monoclonal Antibody to an Insulin-like Growth Factor-2 Receptor (IGF2R)

Targeted Therapy of Osteosarcoma with Radio-labelled Monoclonal Antibody to an Insulin-like Growth Factor-2 Receptor (IGF2R)

A phase I study of convection-enhanced delivery of 124I-8H9 radio-labeled monoclonal antibody in children with diffuse intrinsic pontine glioma: An update with dose-response assessment.

2008 Background: Diffuse intrinsic pontine glioma (DIPG) represents one of the most deadly central nervous system tumors of childhood with a median survival of less than 12 months. Convection-enhanced delivery (CED) has been recently hypothesized as a means for efficiently distributing therapeutic agents within the brain stem. We conducted this study to evaluate CED in children with DIPG. Methods: We performed a standard phase I dose escalation study in patients with non-progressive DIPG 4 to 14 weeks post-completion of radiation therapy. Seven dose levels of a single injection of 124I-8H9 (Omburtamab) (range 0.25 to 4.0 mCi) were studied. Results: 37 children were treated with 34 evaluable for primary and secondary endpoints. The median age at enrollment was 6.8 years old (range 3.2 - 17.9). There was no dose limiting toxicity (DLT). Among adverse events that were at least possibly related to the treatment, there were no grade 4 or 5 events, and only 4 reversible grade 3 events in 4 patients (2 hemiparesis, 1 skin infection and 1 anxiety). Estimations of distribution volumes based on T2-weighted imaging were dose dependent and ranged from 1.5 to 20.8 cm3, and for dose level 7, 10.5 - 19.0 cm3. The mean volume of distribution/volume of infusion ratio (Vd/Vi) was 3.4 ±1.1, and for dose level 7, 3.5 ± 1.0. The mean lesion absorbed dose was 33.3 ± 25.9 Gy, and for dose level 7, 50.1 ± 22.9 Gy. The mean ratio of lesion-to-whole body absorbed dose was 910. The mean volume of distribution/tumor volume ratio on dose level 7 was 82.5%, but the mean tumor overlap was 40.5%. No death occurred as a result of the treatment. Median survival was 15.3 months (n = 29, 95% CI 12.7 - 17.4). Median follow-up time of the 5 surviving patients is 27.2 months (range 11.5 - 72.4). Overall survival rate at 12 months was 64.7% (22/34, 4 alive), and overall survival rate at 24 months 14.7% (5/34, 3 alive). Conclusions: CED in the brain stem of children with DIPG who were previously irradiated is a safe therapeutic strategy. An infusion volume of 4,000 mcl appears to be a reasonable single dose for a target distribution volume but enhanced tumor coverage is likely needed. There seems to be a survival benefit using this therapeutic strategy and outcomes might be dependent on dosimetry and distribution patterns. Clinical trial information: NCT01502917.

Targeted Therapy of Osteosarcoma with Radio-labelled Monoclonal Antibody to an Insulin-like Growth Factor-2 Receptor (IGF2R)

Targeted Therapy of Osteosarcoma with Radio-labelled Monoclonal Antibody to an Insulin-like Growth Factor-2 Receptor (IGF2R)

Clinical indications, image acquisition and data interpretation for white blood cells and anti-granulocyte monoclonal antibody scintigraphy: an EANM procedural guideline

IntroductionRadiolabelled autologous white blood cells (WBC) scintigraphy is being standardized all over the world to ensure high quality, specificity and reproducibility. Similarly, in many European countries radiolabelled anti-granulocyte antibodies (anti-G-mAb) are used instead of WBC with high diagnostic accuracy. The EANM Inflammation & Infection Committee is deeply involved in this process of standardization as a primary goal of the group.AimThe main aim of this guideline is to support and promote good clinical practice despite the complex environment of a national health care system with its ethical, economic and legal aspects that must also be taken into consideration.MethodAfter the standardization of the WBC labelling procedure (already published), a group of experts from the EANM Infection & Inflammation Committee developed and validated these guidelines based on published evidences.ResultsHere we describe image acquisition protocols, image display procedures and image analyses as well as image interpretation criteria for the use of radiolabelled WBC and monoclonal antigranulocyte antibodies. Clinical application for WBC and anti-G-mAb scintigraphy is also described.ConclusionsThese guidelines should be applied by all nuclear medicine centers in favor of a highly reproducible standardized practice.

Tocilizumab Labeling with 99mTechnetium via HYNIC as a Molecular Diagnostic Agent for Multiple Myeloma.

Multiple myeloma is the second most common hematological malignancy. Interleukin-6 (IL-6) is one of the key molecules related to growth, survival and proliferation of myeloma cells. Tocilizumab is a humanized monoclonal antibody directed against receptor of IL-6. To radiolabel Tocilizumab with 99mTechnetium as a potential imaging agents for MM. IL-6R expression was studied by laser confocal microscopy in MM cell lines (U266, NCI-H929 and MM1S). Tocilizumab was derivatized with NHS-HYNIC-Tfa and radiolabeling with 99mTc. Radiochemical stability was determined. In-vitro binding and immunoreactive fraction assays were performed. Biodistribution and SPECT/CT imaging were evaluated in healthy BALB/c and MM-bearing BALB/c nude mice. LCM studies allowed us to demonstrate that U266, NCI-H929 and MM1S cells present high expression of IL-6R in cell membrane. Radiolabeling was carried out in a fast, reproducible, easy and stable way having high radiochemical purity and did not interfere with epitope recognition. The immunoreactive fraction of 99mTc- HYNIC-Tocilizumab was 86.35%. Biodistribution showed a high uptake in liver, spleen, gastrointestinal tract and kidneys. SPECT/CT imaging of MM-bearing BALB/c nude mice showed liver uptake and a high tumor selective uptake at 24 hours. Our results support the potential role of 99mTc-HYNIC-Tocilizumb as a novel MM radiotracer for targeting IL-6 expression in-vivo. We describe the development of a formulation kit to radiolabeling monoclonal antibodies in a clinical setting. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for MM disease.

A phase I study of convection enhanced delivery (CED) of 124I-8H9 radio-labeled monoclonal antibody in children with diffuse intrinsic pontine glioma (DIPG).

2010 Background: Diffuse intrinsic pontine glioma (DIPG) represents one of the most deadly central nervous system tumors of childhood with a median survival of less than 12 months. Convection-enhanced delivery (CED) has been recently hypothesized as a means for augmenting distribution of therapeutic agents within the brain stem. We conducted this study to evaluate CED in children with DIPG. Methods: We performed a standard 3+3 phase I, open-label, dose escalation study in patients with non-progressive DIPG 4 to 14 weeks post-completion or radiation therapy. Seven dose levels of a single injection of 124I-8H9 (range 0.25 to 4.0 mCi, 250 to 4000 mcl) were studied. Results: 25 children were treated. The average age at enrollment 8 years old (range 3-17). There was no dose limiting toxicity (DLT) and adverse events were limited to grade 1 or 2 (CTCAE v4.0). Estimations of distribution volumes were dose dependent and ranged from 1.5 to 20.1 cm3. The mean volume of distribution/volume of infusion (Vd/Vi) was 3.4 (SD 1.2). The mean lesion absorbed dose was 1527 rad/mCi. The mean tumor coverage on dose level 7 was 107%. Conclusions: CED in the brain stem of children with DIPG who were previously irradiated is a safe therapeutic strategy. Up to 4 mCi of 124I-8H9 was well tolerated. An infusion volume of 4000 mcl appears to be a reasonable single dose for good tumor coverage. PET-based dosimetry validates the conceptual basis for direct drug delivery. Based on our finding CED merits further exploration in early phase clinical trials for children with DIPG. Clinical trial information: NCT01502917.

Radiolabeled Antibody Fragment for Preparation of (<sup>177</sup>Lu-DOTA)<sub>m</sub>-PAMAM G3.0-F(ab’)<sub>2</sub> trastuzumab as a Radiopharmaceutical for Cancer Therapy

Several radiolabeled monoclonal antibodies (mAbs) have been used as radioimmunotherapy (RIT) agents for cancer therapy. The use of mAbs as RIT agents is due to their ability to carry effectors, in the form of radionuclides which emit alpha (α) particles, beta (β) particles, or auger electrons, and bind specifically to cancer expressed receptor. This paper reports the preparation of radiolabelled trastuzumab in form of ( 177 Lu-DOTA) m -PAMAM G3-F(ab') 2 -trastuzumab, which will be expected as a potential RIT agent for therapy of breast cancer overexpressed human epidermal growth factor receptor 2 (HER2). Due to its reduced molecular weight, the use of F(ab') 2 -trastuzumab on the aforementioned RIT agent candidate is expected to reach its target much faster compared to the intact trastuzumab. Meanwhile, the role of PAMAM G3 is to increase the specific activity of the radiotherapeutic agent of Lu-177 due to the ability of its 32 –NH 2 functional groups that are able to bind many DOTAs ( £ 31) which in turn can bind a large number of 177 Lu. The preparation was initiated by fragmentation of trastuzumab using pepsin enzyme in 0.02 M acetic acid buffer with a pH of 4.5 to produce F(ab') 2 -trastuzumab with a purity of 95 % after purification with PD-10 column. The F(ab') 2 -trastuzumab was then reacted with succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) to produce SMCC-F(ab') 2 -trastuzumab. The next reaction was to conjugate SMCC-F(ab') 2 -trastuzumab with DOTA-PAMAM G3.0-SH, which was prepared by reaction NHS-DOTA with PAMAM G3.0 and followed by reacting it with 2-iminothiolane to give (DOTA) m -PAMAM G3.0-F(ab') 2 -trastuzumab. Finally, the (DOTA) m -PAMAM G3.0-F(ab') 2 -trastuzumab was radiolabelled with 177 Lu to produce ( 177 Lu-DOTA) m -PAMAM G3.0-F(ab') 2 -trastuzumab, resulting in a radiochemical purity of 98 % after purification with PD-10 column . Received: 31 October 2015 ; Revised: 30 June 2016 ; Accepted: 25 September 2016

The potential of SOCTA as a chelator for radiolabeling of trastuzumab with 99mTc

Radioimmunoscintigraphy is the administration of radio-labeled monoclonal antibodies (MAbs) and imaging with an external gamma camera. In this study, the ability of a new bifunctional N2S2 ligand, (succinimidyl 3,6-diaza-5-oxo-3-[2-((triphenylmethyl)thio)ethyl]-8-[(triphenylmethyl)thio]octanoate) (SOCTA), was evaluated for labeling of trastuzumab (a humanized anti-HER2/neu MAb) with 99mTc. Trastuzumab was labeled with 99mTc using SOCTA. The radiochemical purity, stability, immunoreactivity, biodistribution and imaging study was performed in the mice bearing breast tumor. The good results showed that SOCTA has the good potentials as a chelator for radiolabeling of antibody with 99mTc that needs more investigation in the future.

Effective dose to immuno-PET patients due to metastable impurities in cyclotron produced zirconium-89

Immuno-PET is a nuclear medicine technique that combines positron emission tommography (PET) with radio-labeled monoclonal antibodies (mAbs) for tumor characterization and therapy. Zirconium-89 (89Zr) is an emerging radionuclide for immuno-PET imaging. Its long half-life (78.4h) gives ample time for the production, the administering and the patient uptake of the tagged radiopharmaceutical. Furthermore, the nuclides will remain in the tumor cells after the mAbs are catabolized so that time series studies are possible without incurring further administration of radiopharmarceuticals. 89Zr can be produced in medical cyclotrons by bombarding an yttrium-89 (89Y) target with a proton beam through the 89Y(p,n)89Zr reaction. In this study, we estimated the effective dose to the head and neck cancer patients undergoing 89Zr-based immune-PET procedures. The production of 89Zr and the impurities from proton irradiation of the 89Y target in a cyclotron was calculated with the Monte Carlo code MCNPX and the nuclear reaction code TALYS. The cumulated activities of the Zr isotopes were derived from real patient data in literature and the effective doses were estimated using the MIRD specific absorbed fraction formalism. The estimated effective dose from 89Zr is 0.5±0.2mSv/MBq. The highest organ dose is 1.8±0.2mSv/MBq in the liver. These values are in agreement with those reported in literature. The effective dose from 89mZr is about 0.2−0.3% of the 89Zr dose in the worst case. Since the ratio of 89mZr to 89Zr depends on the cooling time as well as the irradiation details, contaminant dose estimation is an important aspect in optimizing the cyclotron irradiation geometry, energy and time.

Improving Survival in Acute Myeloid Leukemia: Pick the Best Subjects?

Improving Survival in Acute Myeloid Leukemia: Pick the Best Subjects?

Rituximab maintenance versus radio-immunotherapy consolidation in first remission follicular non-Hodgkin lymphoma

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EphA3 Maintains Tumorigenicity and Is a Therapeutic Target in Glioblastoma Multiforme

Significant endeavor has been applied to identify functional therapeutic targets in glioblastoma (GBM) to halt the growth of this aggressive cancer. We show that the receptor tyrosine kinase EphA3 is frequently overexpressed in GBM and, in particular, in the most aggressive mesenchymal subtype. Importantly, EphA3 is highly expressed on the tumor-initiating cell population in glioma and appears critically involved in maintaining tumor cells in a less differentiated state by modulating mitogen-activated protein kinase signaling. EphA3 knockdown or depletion of EphA3-positive tumor cells reduced tumorigenic potential to a degree comparable to treatment with a therapeutic radiolabelled EphA3-specific monoclonal antibody. These results identify EphA3 as a functional, targetable receptor in GBM.

Characteristics of bacterial biofilm associated with implant material in clinical practice

Colonization of bacteria around native host cells or polymeric implant surfaces results in a dense growth on the surface, which leads to infection. The change of a bacterium from a motile planktonic to a nonmotile long chain of growing cells is a complex, regulated process that depends on several factors. The probability of a biofilm-related infection occurrence is between 65 and 80%. This review critically evaluates the mode of biofilm formation on native tissues and orthopedics, dental, cardiac, and urological implants and vascular grafts. The combination of biochemical advancements with conventional microbiological techniques and the use of radio-labeled monoclonal antibodies in imaging techniques, with recent developments in the detection of these biofilm in vivo, would help in designing biomaterials that prevent bacterial adhesion and biofilm formation, and dislodge the formed biofilm, thereby accelerating the product development phase. With the increase in the number of implant-dependent surgeries and biofilm-associated complications, there is a need to counteract and deal with this phenomenon. This has led to various approaches to elucidate the etiology and pathogenesis of the infection. This review critically evaluates the formation, characteristics, pathogenicity and the molecular genetics of both implant- and nonimplant-associated medical biofilm.

A comparison of in vitro methods for determining the membrane receptor expression in cell lines

Determining the number of expressed receptors per cell (NRPC) in cell lines is an important prerequisite for many experimental procedures in biomedical research. This paper focuses on the comparison of a newly developed method of determining NRPC - the Kinetic extrapolation method (KEX) - with the standard saturation method. These two methods, both based on radiolabeled ligand-receptor binding, were compared with the data on receptor expression found using quantified western blotting. Four cell lines with different expressions of epidermal growth factor receptor (EGFR) were chosen for the experiment: A431, HaCaT, HCT116 and HepG2. Two radiolabeled monoclonal antibodies specific for EGFR were used as ligands: [(131)I]-cetuximab and [(131)I]-panitumumab. The classic manual technique based on the saturation of cell receptors was performed on cells seeded in 24-well plates. The KEX method uses the LigandTracer, a special instrument which detects ligand retention in real time from seeded cells onto a rotating Petri dish. The western blot analysis was performed according to the routinely used procedure. A very close accordance between the manual saturation technique and the KEX method was found in all four cell lines used. The NRPC in the cell lines follows the same order using both ligands: A431>HaCaT>HCT116≈HepG2. Similarly, consistent data on EGFR expression in the studied cell lines were obtained using western blot analysis and the radiolabeled ligand binding assays. The KEX method could be as similarly useful for determining receptor expression as is the classic saturation method and western blotting.

Dosage immunoradiométrique de l’intégrine alpha V bêta 3 dans le diagnostic d’infertilité due à l’endométriose

Summary Methods of predicting endometriosis need a sample selected from menstrual cycle day 20 to 24, assaying for alpha V beta 3. by immunoradiometric assay utilizing a double antibody precipitation technique. Monoclonal antibody was iodinated with 125 I and the radiolabelled monoclonal antibody was purified by gel filtration on sephadex G-25. To this purpose, in vitro integrin-binding assays were used to correlate the absence of alpha V beta 3 integrin with endometriosis. There was a highly significant correlation between the levels of extracted integrin and the endometriosis.

Functional imaging of renal cell carcinoma

The incidence of early and advanced-stage renal cell carcinoma (RCC) is increasing. Methods of diagnosing, staging and evaluating tumor burden that are more accurate and reliable than the currently available options are needed in order to identify RCC at a stage at which it is curable and to accurately determine the response to treatment. Functional imaging, particularly with combined PET-CT, might improve accuracy of detection and provide essential information that has been unavailable to date. This approach is against a background in which targeted therapies for metastatic RCC have entered clinical practice in the past few years, further highlighting the importance of accurate imaging for patient selection and for monitoring response to treatment. We outline the current clinical status of functional imaging in RCC using PET-CT, which allows simultaneous capture and co-registration of functional and anatomical data. New radiotracers and approaches-including radiolabeled monoclonal antibodies and imaging of tumor hypoxia-are touched on, and areas of future research discussed.