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Malignant tumours have the remarkable property to express cell surface antigens. Pressman was first reporting that radiolabeled antibodies were capable of organ localization. It was a promising challenge but the expected success and the development of this imaging method was limited by a poor imaging resolution despite a rather good specificity of the antibodies used. Identification of key cell surface markers is opening a new era as potential molecular imaging biomarkers in oncologic applications. Antibodies production has been promoted by the development of engineered fragments with preserved immunological properties and pharmacokinetics optimized for molecular imaging. A good compromise has to be obtained between the biological properties of the antibody and the physical half-life of the radionuclide. Several positron emission tomography (PET) radionuclides such as iodine-124, copper-64, yttrium-86 or zirconium-89 have been the focus of recent immuno-PET studies with inter- esting informative images in preclinical and clinical stud- ies. Thanks to the development of more sensitive new detectors and specific software, molecular imaging meth- ods, particularly PET imaging, allow nowadays the detec- tion of lesions smaller than 5 mm in human. Immuno-PET can potentially be used for tumour detection and identifi- cation at diagnosis, staging and restaging, for treatment selection and monitoring, and during follow-up. Moreover the availability of matched imaging or therapeutic radio- nuclide pairs, such as 124 I/ 131 I, 64 Cu/ 67 Cu and 86 Y/ 90 Y, make easier the quantification of tissue uptake and dosimetry calculation for radioimmunotherapy.

Hybrid systems associating the sharpness of anatomic images coming from computed tomography (CT) and radionuclide functional imaging (SPET or PET) are opening a new era in oncology. This multimodal imaging method is now routinely used for the diagnosis, extent, follow up, treatment response and detection of occult disease in different types of malignancies with a significant impact on the treatment strategy leading for a change for more than 68% of all investigated patients.

As cancer treatment cost soar and the mantra for “personalized medicine” grows louder, we will increasingly be searching for solutions to these diametrically opposed forces. In this review we highlight several exciting novel imaging strategies including MRI, CT, PET SPECT, sentinel node, and ultrasound imaging that hold great promise for improving outcomes through detection of lymph node involvement. We provide clinical data that demonstrate how these evolving strategies have the potential to transform treatment paradigms. J. Surg. Oncol. 2011;103:587–601. © 2011 Wiley-Liss, Inc.

BACKGROUND: Breast cancer recurrence is often suspected on tumor marker rising in asymptomatic patients. The value of fluorine-18 fluorodeoxyglucose (18FDG)–positron emission tomography/computed tomography (PET/CT) imaging to detect recurrence and its subsequent impact on patient management were retrospectively assessed. METHODS: PET/CT scans were performed on 228 asymptomatic patients (mean, 60.8 years; range, 30-91 years) presenting with rising CA 15-3 and/or CEA serum levels. RESULTS: PET/CT scans were positive in 181 patients (79.5%) and normal in 47 patients, whereas 187 true recurrences were diagnosed. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT imaging for detection of breast cancer recurrence were 93.6%, 85.4%, 96.7%, 74.5%, and 92.1%, respectively. When compared with the standard workup available in 67 patients, PET/CT imaging had a higher sensitivity and accuracy (94.5% vs 33% and 94% vs 48%, respectively). Recurrences were confirmed by pathology, conventional imaging techniques, or radiological and clinical follow-up beyond 1 year (mean, 34 months; range, 12-67 years) in 32, 130, and 25 patients, respectively. The diagnosis of recurrence led to a treatment modification in 123 patients (54%). CONCLUSIONS: 18FDG-PET/CT imaging is an efficient technique to detect breast cancer recurrence suspected on tumor marker rising in asymptomatic patients. It may thus contribute to improve patient management, providing an earlier diagnosis with complete whole-body staging as a “one-stop shop” procedure. Cancer 2011. © 2010 American Cancer Society.

Resume Cette observation montre l’interet de la TEP/TDM au FDG dans la caracterisation de tumeurs mammaires bilaterales chez une femme jeune sans facteur de risque carcinologique.

The aim of this study was to evaluate the safety and efficacy of radiolabelled rabbit polyclonal antiferritin antibody in relapsed or refractory Hodgkin's lymphoma. The protocol included a first intravenous injection of In-labelled antiferritin antibody, followed by immunoscintigraphy at 4, 48 and 72 h, and an intravenous injection of Y-labelled antiferritin antibody in the case of tumour targeting. Ten patients were included in the study: median number of chemotherapy regimens: 3; number of autografted patients: 8; number of previously irradiated patients: 9; response to last chemotherapy: six partial response and four progressions. All immunoscintigraphies showed tumour targeting. Nine patients were treated, as the last patient died from progressive Hodgkin's lymphoma before therapeutic injection. Median injected activity was 12 MBq/kg (0.32 mCi/kg). Among the 10 patients who were included in the study, one complete response and six partial responses were observed (overall response rate 70%) with a median duration of response of 8 months (range: 7-12 months). Toxicity was mainly haematological, with grade 1 or 2 neutropenia and anaemia, and grade 2 and 3 thrombocytopenia. The pharmacokinetic study showed that the half-lives of In and Y were almost identical. These results confirm those previously reported and show the therapeutic potential of rabbit polyclonal antiferritin antibody in relapsed or refractory Hodgkin's lymphoma. They therefore justify further multicentre prospective trials.

International audience; Background: The sequence of the beta-subunit of human chorionic gonadotropin (hCG beta varies depending on whether hCG beta is encoded by type I or type II genes. Type II genes are upregulated in trophoblast and cancer but hCG beta can be detected in the serum of nonpregnant women and healthy individuals. We aimed to determine whether monoclonal antibody (mAb) FBT11-II specifically detects hCG beta encoded by type II genes (type II hCG beta). Methods: Competitive inhibition assays with synthetic peptides, immunocytochemical and immunohistochemical studies, type II hCG beta dosing immunoassays and sequencing of CGB genes were performed. Results: Competitive inhibition assays determined that mAb FBT11-II recognizes the type II hCG beta derived peptide. CGB mRNA sequencing of JEG-3 (trophoblastic) and 124 (bladder) cell lines confirmed that JEG-3 expresses type II genes while T24 expresses exclusively type I. FBT11-II only recognizes JEG-expressed hCG beta. Placenta immunohistochemical studies confirmed that type II hCG beta expression is restricted to the syncytiotrophoblast. Immunoassays detected type II hCG beta in serum of patients with either nontrophoblastic cancers or fetal Down syndrome. Conclusion: Type II gene expression can be detected using FBT11-II. This specific recognition could improve the clinical usefulness of assays aimed at either managing aggressive tumors or screening for Down syndrome.

The aim of this study was to assess the performance of FDG PET/CT for the detection of colonic lesions, especially advanced neoplasms (villous or10-mm adenomas, carcinomas). Because of 18F FDG accumulation in adenomatous polyps, PET using FDG can detect early premalignant colorectal lesions.FDG PET/CT studies performed for a 1-year period in 1,716 consecutive patients with various malignant diseases, except colorectal cancer, were retrospectively reviewed. PET images obtained 1 hr after FDG injection and non-contrast CT images used for attenuation correction were fused for analysis. Of 45 patients showing intense focal colonic FDG uptake, 20 patients (with 21 foci) underwent a colonoscopic investigation, and, when necessary, polyp resection. The intensity of FDG uptake was quantified using the standardized uptake value (SUV(max)).The FDG colonic foci were associated with 18 colonoscopic abnormalities in 15 patients, with no colonic abnormality detected in five patients (false-positive [FP] results). Histopathologic findings revealed advanced neoplasms in 13 patients (13 villous adenomas and three carcinomas) and two cases of hyperplastic polyps. A difference in the mean SUV(max) was found between FP and true-positive colonic FDG foci but was not statistically significant (p = 0.14).Presence of a focal colonic FDG uptake incidental finding on a PET/CT scan justifies a colonoscopy to detect (pre-)malignant lesions. The fusion of PET and CT images allows an accurate localization of the lesions. PET/CT is a useful tool to differentiate pathologic from physiologic FDG uptake.

Resume Le role potentiel de la TEP-18FDG a ete evalue dans la recherche d’une maladie occulte chez des patients traites pour un cancer et presentant une elevation isolee d’un marqueur tumoral serique. Methode. – Six cent-quinze patients, 37 a 77 ans, traites pour un cancer du sein (291), un cancer colorectal (201) ou un cancer de l’ovaire (123) ont ete etudies. La TEP-18FDG a ete realisee avec une camera hybride couplee a un scanner et correlee avec l’evolution clinique, les methodes d’imagerie conventionnelle focalisee et les resultats pathologiques. Resultats. – La TEP-18FDG a ete positive pour 571 patients. Avec une sensibilite de 96,7 % et une valeur predictive positive de 94,7 %, une maladie evolutive a ete identifiee pour 87,3 % des patients avec une precession sur les signes cliniques de 4-11 mois. Conclusion. – Ces resultats encourageants justifie la mise en route de nouveaux protocoles comparant l’attitude therapeutique classique a un traitement precoce avec comme cible le taux des marqueurs seriques et la lesion detectee avec la TEP-18FDG.

Resume Le texte de cette table ronde a ete retranscrit durant la session « Avancees dans la Biologie des Cancers » pendant le 18e colloque CORATA (Nantes, 26 octobre 2001).

resume L'utilisation d'anticorps monoclonaux d'origine murine a visee diagnostique et therapeutique se developpe en cancerologie. Une reponse immunitaire avec anticorps anti-souris circulants (AAS) apparait chez certains patients. 692 dosages d'AAS par technique Elisa Medac ont ete realises chez 211 patients ayant eu une ou plusieurs immunoscintigraphies par anticorps monoclonaux anti-ACE, OC 125 et B 72.3. Le seuil de positivite avec cette technique est de 200 ng mL−1. Chez les sujets normaux (n = 18) ou chez les patients avant injection (n = 209), nous avons obtenu respectivement une concentration moyenne de 7,2 ± 11,5 et 4,1 ± 13,9 ng mL−1 d'AAS. Apres une premiere immunoscintigraphie, 34/179 (19,0 %) des patients ont developpe des AAS, dans un delai moyen (n = 8) de 79,5 ± 63,2 j. Le retour a une concentration inferieure a 200 ng mL−1 s'est effectue en 246,0 ± 205,5 j (n = 6). Parmi 22 patients ayant eu deux immunoscintigraphies, 20 n'avaient pas d'AAS avant la deuxieme injection, trois n'ont pas eu de dosages ulterieurs, 9/19 sont devenus positifs, deux patients positifs avant la seconde injection ont eleve fortement leur concentration en anticorps. 1/2 patients ayant trois immunoscintigraphies est reste constamment negatif. L'intensite et la duree de l'immunisation, variables selon les patients, imposent des prelevements repetes pour detecter la presence d'anticorps anti-souris.

The purpose of this pilot study was to assess whether outcome in metastatic or recurrent breast cancer patients is related to metabolic response to endocrine therapy determined by (18)F-FDG PET/CT.The study group comprised 22 patients with breast cancer (age 58 ± 11 years, mean ± SD) who were scheduled to receive endocrine therapy. They were systematically assessed by PET/CT at baseline and after a mean of 10 ± 4 weeks for evaluation of response after induction. All patients demonstrated FDG-avid lesions on the baseline PET/CT scan. The metabolic response was assessed according to EORTC criteria and based on the mean difference in SUV(max) between the two PET/CT scans, and the patients were classified into four groups: complete or partial metabolic response, or stable or progressive metabolic disease (CMR, PMR, SMD and PMD, respectively). All patients were followed in our institution.Metastatic sites were localized in bone (n = 15), lymph nodes (n = 11), chest wall (n = 3), breast (n = 5), lung (n = 3), soft tissue (n = 1) and liver (n = 1). PMR was observed in 11 patients (50%), SMD in 5 (23%) and PMD in 6 (27%). The median progression-free survival (PFS) times were 20, 27 and 6 months in the PMR, SMD and PMD groups, respectively. PFS in the SMD group differed from that in the PMR and SMD groups (p0.0001).Metabolic response assessed by FDG PET/CT imaging in patients with metastatic breast cancer treated with endocrine therapy is predictive of the patients' PFS.

The combined effect of cryotherapy and chemotherapy was studied in 12 patients with bronchial carcinoma. Radiolabeled (57 Co) Bleomycin (BLM) was injected intravenously and initial detection was carried out with a gamma-camera. Plasma half-life and clearance of 57 Co-BLM, as well as tumor/normal tissues ratios were calculated. The same protocol was performed 15 days later immediately after cryotherapy. A mean increase of 30% of radiolabeled BLM was found in the tumor area after cryotherapy, and pharmacokinetic data were significantly different after cryotherapy. The vascular component of cryodestruction offers an explanation for these results, with trapping of the anticancer drug in the tumor and immediately surrounding area due to vascular stasis. It seems that chemotherapy may be more effective after cryotherapy, and a multicenter study is in progress to evaluate the association of cryo-chemotherapy in France.

Neuroendocrine (NE) cancers are usually suspected on clinical symptoms related to their metabolically active peptide secretion into the circulatory system. The most effective treatment is surgery and a preoperative accurate localization of these slow growing tumors is needed. Combined anatomical (CT) and molecular imaging modalities using single-photon emission computed tomography (SPET) with radiolabeled pentetreotide have been developed in routine, and we report here the potential of SPECT/CT image fusion for diagnosis, staging, and evaluation of treatment efficacy of NE cancers.

In patients with cervical lymph node metastases from unknown primary tumour (UPT), the primary tumour is frequently localized in the head and neck area. Because the detection of the primary tumour is of importance to optimize the patient's management and allows a targeted therapy, the performances of hybrid positron emission tomography-computed tomography (PET-CT) using fluorodeoxyglucose (FDG) were evaluated in a retrospective study.Thirty-eight consecutive patients with cervical lymph node metastases, and in whom the primary was not detected by the comprehensive diagnostic work-up including endoscopy and conventional imaging methods, were referred for a PET-CT scan.PET-CT was positive with an increased FDG focal uptake suggesting the potential primary site in 68% of patients (26/38), which guided the biopsies during a second rigid panendoscopy in 17 of these 26 patients: 13 primary tumours were then histologically proven. PET-CT showed distant lesions in three patients. It had treatment-related implications in 23/38 patients (60%), consisting of modification of radiation planning, surgery or abstention from surgery.Hybrid FDG-PET-CT is helpful for the detection of a potential head and neck primary tumour. Furthermore, hybrid FDG-PET-CT has the ability to diagnose occult or distant second tumour and metastatic disease and modify patient management.

Trophoblast research over the past decades has underlined the striking similarities between the proliferative, migratory and invasive properties of placental cells and those of cancer cells. This review recapitulates the numerous key molecules, proto-oncogenes, growth factors, receptors, enzymes, hormones, peptides and tumour-associated antigens (TAAs) expressed by both trophoblastic and cancer cells in an attempt to evaluate the genes and proteins forming molecular circuits and regulating the similar behaviours of these cells. Among the autocrine and paracrine loops that might be involved in the strong proliferative capacity of trophoblastic and cancer cells, epidermal growth factor (EGF)/EGF receptor (EGFR), hepatocyte growth factor (HGF)/HGF receptor (HGFR) (Met) and vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) loops may play a predominant role. Similar mechanisms of migration and invasion displayed by trophoblastic and malignant cells comprise alterations in the adhesion molecule phenotype, including the increased expression of alpha1beta1 and alphavbeta3 integrin receptors, whereas another critical molecular event is the down-regulation of the cell adhesion molecule E-cadherin. Among proteases that may play an active role in the invasive capacities of these cells, accumulating evidence suggests that matrix metalloproteinase-9 (MMP-9) expression/activation is a prerequisite. Finally, an overview of molecular circuitries shared by trophoblast and cancer cells reveals that the activation of the phosphatidylinositol 3'-kinase (PI3K)/AKT axis has recently emerged as a central feature of signalling pathways used by these cells to achieve their proliferative, migratory and invasive processes.

Progress toward targeting cancer cells is a multi-disciplinary endeavor. In addition to the surgical and oncology specialties, radiologists collaborate with mathematicians, computer scientists, and physicists, in a constant effort to incrementally improve upon the current imaging modalities. Recently, radiologists have formed collaborations with molecular biologists and chemists in order to develop molecular agents that target cancer cells via receptor-substrate or specific physiochemical interactions. In this review, we summarize selected efforts toward molecular targeting of the lymphovascular system. Standard imaging modalities, positron emission tomography, single photon emission tomography, and ultrasound, are reviewed as well as, the targeted introduction of substances for endolymphatic therapy. We also review the current status of sentinel lymph node mapping with radiocolloids and the application of molecular targeting for the development of a radiopharmaceutical specifically designed for sentinel lymph node mapping.

An isolated increase of blood tumor marker CA 15.3 in breast cancer is considered a sensitive indicator for occult metastatic disease but by itself is not sufficient for initiating therapeutic intervention. We investigated the potential of camera-based positron emission tomogaphy (PET) imaging using [18F]-fluorodeoxyglucose (FDG) to detect clinically occult recurrences in 132 female patients (age, 35-69 years) treated for breast cancer, all presenting with an isolated increase in blood tumor marker CA 15.3 without any other evidence of metastatic disease. FDG results were correlated to pathology results or to a sequentially guided conventional imaging method. One hundred nineteen patients were eligible for correlations. Positive FDG scans were obtained for 106 patients, including 89 with a single lesion and 17 with 2 or more lesions. There were 92 true-positive and 14 false-positive cases, 10 of which became true positive within 1 year. Among the 13 negative cases, 7 were false negative and 6 were true negative. Camera-based PET using FDG has successfully identified clinically occult disease with an overall sensitivity of 93.6% and a positive predictive value of 96.2%. The smallest detected size was 6 mm for a lymph node metastasis (tumor to nontumor ratio, 4:2). FDG camera-based PET localized tumors in 85.7% of cases suspected for clinically occult metastatic disease on the basis of a significant increase in blood tumor marker. A positive FDG scan associated with an elevated CA 15.3 level is most consistent with metastatic relapse of breast cancer.

Background: Radioimmunotherapy (RIT) is an innovative, promising approach to treatment of relapsed or refractory (RR) Hodgkin lymphoma (HL). RIT confers the dual benefit of specific-antibody recognition of tumor regions coupled with selective irradiation of antigen-presenting cells and cells contiguous/proximal to tumor sites. We are developing a rabbit polyclonal IgG antibody directed against human ferritin (a tumor-associated antigen in HL) that is tightly chelated - via stable thiourea binding with bifunctional NCS-DOTA - to 90Yttrium (90Y, a pure β-emitting radioisotope) for treatment of RR-HL. An earlier study in RR HL patients of 90Y-antiferritin using a DTPA chelator at doses from 11.1-18.5 MBq/kg (0.3-0.5 mCi/kg) produced 22%-86% overall response rates (CR + PR) with median response durations of 6-8 months (Vriesendorp et al., Clinical Cancer Res, 1999; 5:3324S-3329S). Methods: This study in RR-HL patients conducted at two centers was designed to evaluate the safety and tolerability of single ascending doses of 90Y-antiferritin in MBq/kg (mCi/kg): 7.4 (0.2), 11.1 (0.3), 14.8 (0.4), then in increments of 2 MBq/kg (0.05 mCi/kg) until reaching the maximum tolerated dose (MTD) in order to select dosing for further investigations (one dose step below MTD). Patients ranging from 15 to 75 years of age who had received 2-4 courses of chemotherapy, performance status ≤2, bone marrow involvement ≤25% and no CNS HL who signed informed consent could receive a diagnostic IV injection of 2 mg antiferritin labeled with 111MBq (3 mCi) 111Indium (Day -7). Patients with positive tumor targeting by immunoscintigraphy were eligible for therapeutic dosing with 90Y-antiferritin (Day 1, Week 1). Death, prolonged grade 4 (G4) hematologic toxicity through study Week 11 or any G4 nonhematological toxicity/infection were the prespecified dose-limiting toxicities (DLTs). The MTD was reached when 2 of 2 (at the 7.4 or 11.1 MBq/kg dose levels) or 3 of 3 patients (at higher dose levels) experienced DLTs. Criteria for safety evaluation included laboratory parameters, human anti-rabbit antibodies (HARA), physical examination, chest X-ray, ECG, adverse events (AEs) and overall safety assessment at Week 11. All dose escalations required authorization by the Drug Safety Monitoring Board (DSMB) who reviewed data on an ongoing basis. Results: N=17 patients (8 M, 9 F) with RR-HL were enrolled; 4 were dismissed before treatment with 90Y-antiferritin (2 had no measurable disease [PET scan], 1 had negative tumor targeting, 1 was obese and dose could not be calculated). The mean age of 13 patients (6M, 7F) treated with 90Y-antiferritin was 37.6 years (18-64). Two patients each received single doses of 7.4 and 11.1 MBq/kg, and 3 each received 14.8 and 16.65 MBq/kg. A second block of 3 patients received 14.8 MBq/kg after the MTD (16.65 MBq/kg) was established. Most hematologic toxicities were G2 or G3. At the 16.65 MBq/kg dose level, 1 patient experienced prolonged G4 thrombocytopenia and another experienced prolonged G4 thrombocytopenia and lymphopenia. Four patients experienced serious AEs, most of which were of hematologic nature, possibly or probably-related to study drug. There were no deaths on study, and no hepatic, lung or cardiac toxicities were observed. HARA assay was positive in only one of 9 patients who were tested. Conclusions: This study established that the MTD of 90Y-antiferritin in patients with RR HL was 16.65 MBq/kg (0.45 mCi/kg). In these heavily-pretreated and immunocompromised patients with RR HL, 90Y-antiferritin was very well-tolerated at doses up to 14.8 MBq/kg (0.4 mCi/kg), which will be considered as the initial dose in a forthcoming phase 3 safety and efficacy study in this population. Disclosures Decaudin: MatBiopharma: Research Funding. Kadouche:Alissa Pharma: Employment, Equity Ownership. Allard:Alissa Pharma: Employment, Equity Ownership.

PURPOSE: The study contained herein was undertaken to evaluate the accuracy of radiolabeled human monoclonal antibody, 88BV59H21-2V67-66 (88BV59 or HumaSPECT®-Tc), in predicting disease resectability in presurgical subjects with recurrent, metastatic, or occult colorectal carcinoma. METHODS: A total of 219 patients with disease visualized on computed tomographic scan (recurrent or metastatic disease) or with negative or equivocal computed tomographic scan and rising carcinoembryonic antigen serum levels (occult group) received technetium Tc 99m-labeled 88BV59 intravenously. Planar and single photon emission computed tomographic images were obtained 14 to 20 hours postinfusion, before surgery. The ability of computed tomographic and HumaSPECT®-Tc imaging to define the extent of disease and to predict resectability was evaluated based on surgical and histopathologic results. RESULTS: In patients with recurrent or metastatic disease (170 evaluable patients), the accuracy of predicting non-resectability of disease was significantly greater (P

The authors report 2 cases of bronchial carcinoid tumor (BCT). One had a typical and the other had an atypical histologic pattern. BCTs represent 1 to 2% of all lung cancers and are usually located in the hilar or perihilar areas. They can be associated with infectious processes. Typical ca

The use of radiolabeled murine monoclonal antibodies (MoAbs) for cancer immunodetection has been limited by the development of human antimouse antibodies (HAMA). Human monoclonal antibodies do not elicit a significant human antihuman (HAHA) response. The generation and production of human monoclonal antibodies met with technical difficulties that resulted in delaying their clinical testing. Human monoclonal antibodies of all isotypes have been obtained. Most were immunoglobulin (Ig) M directed against intracellular antigens. Two antibodies, 16.88 (IgM) and 88BV59 (IgG3k), recognize different epitopes on a tumor-associated antigen, CTA 16.88, homologous to cytokeratins 8, 18, and 19. CTA 16.88 is expressed by most epithelial-derived tumors including carcinomas of the colon, pancreas, breast, ovary, and lung. The in vivo targeting by these antibodies is related to their localization in nonnecrotic areas of tumors. Repeated administration of 16.88 over 5 weeks to a cumulative dose of 1,000 mg did not elicit a HAHA response. Two of 53 patients developed a low titer of HAHA 1 to 3 months after a single administration of 88BV59. Planar imaging of colorectal cancer with Iodine-131 (131I)-16.88 was positive in two studies in 9 of 12 and 16 of 20 patients preselected by immunohistochemistry. Tumors less than 2 cm in diameter are usually not detected. The lack of immunogenicity and long tumor residence time (average = 17 days) makes 16.88 a good candidate for therapy. Radioimmunlymphoscintigraphy with indium-111 (111In)-LiLo-16.88 administered by an intramammary route was used in the presurgical staging of primary breast cancer. The negative predictive value of lymph node metastases for tumors less than 3 cm was 90.5%. Planar and single photon emission computed tomography imaging of colorectal carcinoma with technetium-99m (99mTc) 88BV59 was compared with computed tomography (CT) scan in 36 surgical patients. The antibody scan was more sensitive than the CT scan in detecting abdominal and pelvic tumors: 68% versus 40% (P.05). The combination of antibody scan and CT scan was superior to CT scan alone: 80% versus 40% (P.01). Lesions as small as 0.5 cm in diameter were detected by antibody scan. The CT scan appears superior to the antibody scan for liver metastases. Patients with a high serum titer of HAMA from previous exposure to murine antibodies were successfully imaged. Antibody scans obtained with 99mTc-88BV59 have imaging characteristics similar to murine antibody scans obtained with radiolabeled IgGs. The absence or weak immunogenicity of the human monoclonal antibodies makes them good candidates for radioimmunodetection and radioimmunotherapy.

In the preceding chapter we discussed the various endoscopic techniques available to the chest physician. These techniques are used to treat cancerous lesions in 80% of cases. Cryotherapy may be associated with other modalities for the treatment of bronchial carcinoma, for example radiotherapy and chemotherapy — these are studies which have been initiated but they are hardly beyond the experimental stage, however early results are encouraging and there seems to be a possible synergistic effect of combined cryotherapy with both radiotherapy and chemotherapy. If a synergistic effect is proven then the indications for cryotherapy will obviously be widened.

The aim of this study was to evaluate the safety and efficacy of radiolabelled DTPA-chelated rabbit polyclonal antiferritin antibody (Ab) in relapsed or refractory HL. The protocol included a first intravenous injection of 111Indium-labelled antiferritin Ab followed by immunoscintigraphy at 4, 48, and 72 hours and intravenous injection of 90Yttrium-labelled antiferritin Ab in the case of tumour targeting. Ten patients were included in the study: median number of chemotherapy regimens: 3; number of autografted pts: 8; number of previously irradiated pts: 9; response to last chemotherapy: 6 PR and 4 progressions. All immunoscintigraphies showed tumour targeting. Nine patients were treated, as the last patient died from progressive HL before therapeutic injection. Median injected activity was 12 MBq/kg (0.32 mCi/kg). Among the ten patients who were included in the study, 1 CR and 6 PR were observed (ORR 70%) with a median duration of response of 8 months (range: 7–12 months). Toxicity was mainly haematological, with grade 1 or 2 neutropenia and anaemia, and grade 2 and 3 thrombocytopenia. The pharmacokinetic study showed that the half-lives of 111Indium and 90Yttrium were almost identical. These results confirm those previously reported in the literature and show the therapeutic potential of rabbit polyclonal antiferritin Ab in relapsed or refractory HL. On the basis of all these results, MATBioPharma proposed to test a radioimmunotherapy with polyclonal antiferritin antibodies (Abs) in patients with refractory or relapsed HL. The treatment is constituted with chelated rabbit polyclonal antiferritin Abs to be loaded with 111Indium for the diagnosis of the tumour(s) by immunoscintigraphy and with 90Yttrium for the treatment of the tumour(s). A phase I study is still ongoing at the Institut Curie / Centre René Huguenin (France) to evaluate the safety and tolerability of ascending doses of 90Yttrium antiferritin until the maximum tolerated dose (MTD) is reached and to select a dose for further investigation (one dose step below MTD). A pharmacokinetics is concomitantly performed to determine dose linearity and pharmacokinetic parameters of increasing 90Y-Ab and Ab. The second dose level will be completed in the third quarter 2007 and available data on immunoscintigraphy, safety, and efficacy of included HL patients will be provided for the 49th ASH congress.

14515 Background: In vitro spheroid model using cancer cell lines is widely admitted to mimic in vivo micro tumors, including micrometastases. Floating spheroid cell cluster culture has been recently used for normal and cancer stem cell expansion. Spontaneously spheroids generated in vivo have been only studied in ovarian cancer ascites while organoid aggregates have been sometimes observed in the establishment of human colon cancer cell lines. In this study, we investigated whether spontaneous spheroid aggregates from colon cancer could be isolated and characterized. Methods: 127 colorectal primary tumor specimens have been collected and mechanically dissociated into small fragments, which were then shortly cultured on cell plastic flask. Production of spheroid- like structures, referred to as colospheres, was examined at Day 1 and colospheres were gathered for phenotypic characterization. Results: Colospheres were successfully generated from 67 surgical specimens (53%). The capacity to form colospheres was strictly restricted to tumor tissue: dissociated normal colon mucosa never generated colospheres and colospheres were formed exclusively by cancer cells. The ability to generate colospheres was demonstrated to be significantly related to tumor aggressiveness, according to nodal status and AJCC’s stages (Chi-2 test, p No significant financial relationships to disclose.