Potential of TSPO radioligands: Bridging brain tumor diagnostics to the peripheries.

Translocator protein (TSPO) is involved in several cellular mechanisms such as steroidogenesis, immunomodulation, cell proliferation and differentiation. Overexpressed in several neurodegenerative diseases and brain cancer, TSPO radioligands have been developed over the last 20 years in positron emission tomography (PET) imaging. Recently, TSPO radioligands have extended beyond their initial application due to their specific binding to activated macrophages, making them a compelling biomarker for deciphering the intricacies of the tumor microenvironment (TME). In this review, we synthesized recent progress from the evaluation of TSPO-specific PET tracers in various peripheral tumor models and highlighted the hurdles and limitations associated with heterogeneous uptake in healthy tissue and tumor regions to achieve the clinical development of such a radiotracer.

Promising clinical performance of pretargeted immuno-PET with anti-CEA bispecific antibody and gallium-68-labelled IMP-288 peptide for imaging colorectal cancer metastases: a pilot study.

INTRODUCTION: This pilot study evaluated the imaging performance of pretargeted immunological positron emission tomography (immuno-PET) using an anti-carcinoembryonic antigen (CEA) recombinant bispecific monoclonal antibody (BsMAb), TF2 and the [68Ga]Ga-labelled HSG peptide, IMP288, in patients with metastatic colorectal carcinoma (CRC). PATIENTS AND METHODS: Patients requiring diagnostic workup of CRC metastases or in case of elevated CEA for surveillance were prospectively studied. They had to present with elevated CEA serum titre or positive CEA tumour staining by immunohistochemistry of a previous biopsy or surgical specimen. All patients underwent endoscopic ultrasound (EUS), chest-abdominal-pelvic computed tomography (CT), abdominal magnetic resonance imaging (MRI) and positron emission tomography using [18F]fluorodeoxyglucose (FDG-PET). For immuno-PET, patients received intravenously 120 nmol of TF2 followed 30 h later by 150 MBq of [68Ga]Ga-labelled IMP288, both I.V. The gold standard was histology and imaging after 6-month follow-up. RESULTS: Eleven patients were included. No adverse effects were reported after BsMAb and peptide injections. In a per-patient analysis, immuno-PET was positive in 9/11 patients. On a per-lesion analysis, 12 of 14 lesions were positive with immuno-PET. Median SUVmax, MTV and TLG were 7.65 [3.98-13.94, SD 3.37], 8.63 cm3 [1.98-46.64; SD 14.83] and 37.90 cm3 [8.07-127.5; SD 43.47] respectively for immuno-PET lesions. Based on a per-lesion analysis, the sensitivity, specificity, positive-predictive value and negative-predictive value were, respectively, 82%, 25%, 82% and 25% for the combination of EUS/CT/MRI; 76%, 67%, 87% and 33% for FDG-PET; and 88%, 100%, 100% and 67% for immuno-PET. Immuno-PET had an impact on management in 2 patients. CONCLUSION: This pilot study showed that pretargeted immuno-PET using anti-CEA/anti-IMP288 BsMAb and a [68Ga]Ga-labelled hapten was safe and feasible, with promising diagnostic performance. TRIAL REGISTRATION: ClinicalTrials.gov NCT02587247 Registered 27 October 2015.

Prognostic value of metabolic parameters and clinical impact of ¹8F-fluorocholine PET/CT in biochemical recurrent prostate cancer.

PURPOSE: To evaluate the therapeutic impact of (18)F-fluorocholine (FCH) PET/CT in biochemical recurrent prostate cancer (PC) and to investigate the value of quantitative FCH PET/CT parameters in predicting progression-free survival (PFS). METHODS: This retrospective study included 172 consecutive patients with PC who underwent FCH PET/CT for biochemical recurrence. Mean rising PSA was 10.7 ± 35.0 ng/ml. Patients with positive FCH PET were classified into three groups: those with uptake only in the prostatic bed, those with locoregional disease, and those with distant metastases. Referring physicians were asked to indicate the hypothetical therapeutic strategy with and without the FCH PET/CT results. Clinical variables and PET parameters including SUVmax, SUVpeak, SUVmean, total lesion choline kinase activity (TLCKA) and standardized added metabolic activity (SAM) were recorded and a multivariate analysis was performed to determine the factors independently predicting PFS. RESULTS: In 137 of the 172 patients, the FCH PET/CT scan was positive, and of these, 29.9 % (41/137) had prostatic recurrence, 42.3 % (58/137) had pelvic lymph node recurrence with or without prostatic recurrence, and 27.7 % (38/137) had distant metastases. The FCH PET/CT result led to a change in treatment plan in 43.6 % (75/172) of the 172 patients. Treatment was changed in 49.6 % (68/137) of those with a positive FCH PET/CT scan and in 20 % (7/35) of those with a negative FCH PET/CT scan. After a median follow-up of 29.3 months (95 % CI 18.9 - 45.9 months), according to multivariate analysis age <70 years, SAM ≥23 and SUVmean ≥3 were parameters independently predicting PFS. A nomogram constructed using the three parameters showed 49 months of PFS in patients with the best scores (0 or 1) and only 11 months in patients with a poor score (score 3). CONCLUSION: This study indicates that a positive FCH PET result in PC patients with biochemical recurrence predicts a shorter PFS and confirms the major impact of the FCH PET result on the management of biochemical recurrent PC.

Assessment of a fully 3D Monte Carlo reconstruction method for preclinical PET with iodine-124.

Iodine-124 is a radionuclide well suited to the labeling of intact monoclonal antibodies. Yet, accurate quantification in preclinical imaging with I-124 is challenging due to the large positron range and a complex decay scheme including high-energy gammas. The aim of this work was to assess the quantitative performance of a fully 3D Monte Carlo (MC) reconstruction for preclinical I-124 PET. The high-resolution small animal PET Inveon (Siemens) was simulated using GATE 6.1. Three system matrices (SM) of different complexity were calculated in addition to a Siddon-based ray tracing approach for comparison purpose. Each system matrix accounted for a more or less complete description of the physics processes both in the scanned object and in the PET scanner. One homogeneous water phantom and three heterogeneous phantoms including water, lungs and bones were simulated, where hot and cold regions were used to assess activity recovery as well as the trade-off between contrast recovery and noise in different regions. The benefit of accounting for scatter, attenuation, positron range and spurious coincidences occurring in the object when calculating the system matrix used to reconstruct I-124 PET images was highlighted. We found that the use of an MC SM including a thorough modelling of the detector response and physical effects in a uniform water-equivalent phantom was efficient to get reasonable quantitative accuracy in homogeneous and heterogeneous phantoms. Modelling the phantom heterogeneities in the SM did not necessarily yield the most accurate estimate of the activity distribution, due to the high variance affecting many SM elements in the most sophisticated SM.

Which radionuclide, carrier molecule and clinical indication for alpha-immunotherapy?

Beta-emitting radionuclides are not able to kill isolated tumor cells disseminated in the body, even if a high density of radiolabeled molecules can be targeted at the surface of these cells because the vast majority of emitted electrons deliver their energy outside the targeted cells. Alpha-particle emitting radionuclides may overcome this limitation. It is thus of primary importance to test and validate the radionuclide of choice, the most appropriate carrier molecule and the most promising clinical indication. Four α-particle emitting radionuclides have been or are clinically tested in phase I studies namely 213Bi, 225Ac, 212Pb and 211At. Clinical safety has been documented and encouraging efficacy has been shown for some of them (213Bi and 211At). 211At has been the most studied and could be the most promising radionuclide but 225Ac and 212Pb are also of potential great interest. Any carrier molecule that has been labeled with ß-emitting radionuclides could be labeled with alpha particle-emitting radionuclide using, for some of them, the same chelating agents. However, the physical half-life of the radionuclide should match the biological half-life of the radioconjugate or its catabolites. Finally everybody agrees, based on the quite short range of alpha particles, on the fact that the clinical indications for alpha-immunotherapy should be limited to the situation of disseminated minimal residual diseases made of small clusters of malignant cells or isolated tumor cells.

Clinical NECR in 18F-FDG PET scans: optimization of injected activity and variable acquisition time. Relationship with SNR.

The injected activity and the acquisition time per bed position for 18F-FDG PET scans are usually optimized by using metrics obtained from phantom experiments. However, optimal activity and time duration can significantly vary from a phantom set-up and from patient to patient. An approach using a patient-specific noise equivalent count rate (NECR) modelling has been previously proposed for optimizing clinical scanning protocols. We propose using the clinical NECR on a large population as a function of the body mass index (BMI) for deriving the optimal injected activity and acquisition duration per bed position. The relationship between the NEC and the signal-to-noise ratio (SNR) was assessed both in a phantom and in a clinical setting. 491 consecutive patients were retrospectively evaluated and divided into 4 BMI subgroups. Two criteria were used to optimize the injected activity and the time per bed position was adjusted using the NECR value while keeping the total acquisition time constant. Finally, the relationship between NEC and SNR was investigated using an anthropomorphic phantom and a population of 507 other patients. While the first dose regimen suggested a unique injected activity (665 MBq) regardless of the BMI, the second dose regimen proposed a variable activity and a total acquisition time according to the BMI. The NEC improvement was around 35% as compared with the local current injection rule. Variable time per bed position was derived according to BMI and anatomical region. NEC and number of true events were found to be highly correlated with SNR for the phantom set-up and partially confirmed in the patient study for the BMI subgroup under 28 kg m(-2) suggesting that for the scanner, the nonlinear reconstruction algorithm used in this study and BMI < 28 kg m(-2), NEC, or the number of true events linearly correlated with SNR(2).

Comparative analysis of multiple myeloma treatment by CD138 antigen targeting with bismuth-213 and Melphalan chemotherapy.

INTRODUCTION: Multiple myeloma (MM) is a B-cell malignancy of terminally differentiated plasma cells within the bone marrow. Despite intense research to develop new treatments, cure is almost never achieved. Alpha-radioimmunotherapy (RIT) has been shown to be effective in vivo in a MM model. In order to define where alpha-RIT stands in MM treatment, the aim of this study was to compare Melphalan, MM standard treatment, with alpha-RIT using a [213Bi]-anti-mCD138 antibody in a syngeneic MM mouse model. METHODS: C57BL/KaLwRij mice were grafted with 1 × 10(6) 5T33 murine MM cells. Luciferase transfected 5T33 cells were used for in vivo localization. The first step of the study was to assess the dose-response of Melphalan 21 days after engraftment. The second step consisted in therapeutic combination: Melphalan followed by RIT at day 22 or day 25 after engraftment. Toxicity (animal weight, blood cell counts) and treatment efficacy were studied in animals receiving no treatment, injected with Melphalan alone, RIT alone at day 22 or day 25 (3.7 MBq of [213Bi]-anti-CD138) and Melphalan combined with alpha-RIT. RESULTS: Fifty percent of untreated mice died by day 63 after MM engraftment. In mice treated with Melphalan alone, only the 200 µg dose improved median survival. No animal was cured after Melphalan treatment whereas 60% of the mice survived with RIT alone at day 22 after tumor engraftment with only slight and reversible hematological radiotoxicity. No therapeutic effect was observed with alpha-RIT 25 days after engraftment. Melphalan and alpha-RIT combination does not improve overall survival compared to RIT alone, and results in increased leukocyte and red blood cell toxicity. CONCLUSIONS: Alpha-RIT seems to be a good alternative to Melphalan. Association of these two treatments provides no benefit. The perspectives of this work would be to evaluate RIT impact on the regimens incorporating the novel agents bortezomide, thalidomide and lenalidomide.

18F-FDG PET/CT for the assessment of gastrointestinal GVHD: results of a pilot study.

This prospective pilot study aimed to evaluate the predictive value of (18)F-FDG PET/CT for early diagnosis of acute gastrointestinal GVHD (GI-GVHD). In all, 42 consecutive patients who received allo-SCT were included. (18)F-FDG PET/CT was systematically performed at a median of 28 (range, 24-38) days after allo-SCT. (18)F-FDG PET/CT data review was positive in 15 cases (36%) (9 true positive (TP) cases and 6 false positive (FP) cases) and negative in 27 cases (64%; 26 true negative (TN) cases and 1 false negative (FN) case) at visual analysis. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of (18)F-FDG PET/CT for the diagnosis of acute GI-GVHD were, respectively, 81%, 90%, 60%, 96% and 83%. There were no significant differences of SUVmax values between grade 1-2 GI-GVHD and severe grade 3-4 GI-GVHD. Overall, these preliminary findings suggested that the inflammatory activity of the gastrointestinal tract associated with acute GI-GVHD could be assessed by (18)F-FDG PET/CT suggesting that noninvasive (18)F-FDG PET/CT could become a valuable examination to be performed shortly before endoscopy to map acute GI-GVHD lesions, guide the biopsy sites and choose the appropriate endoscopic procedure, especially in those asymptomatic patients with a positive (18)F-FDG PET/CT.

The role of FDG-PET scanning in assessing lymphoma in 2012.

Positron emission tomography (PET) has a proven role in the assessment diffuse large B-cell lymphoma (DLBCL) and Hodgkin's lymphoma (HL). The clinical impact of PET carried out at the end of the patient's course of treatment is undeniable and recommendations must be followed in the interpretation of these examinations. PET is highly recommended as part of the initial investigations of these diseases because it can be used as a reference for the interpretation at treatment completion and allows disease spread to be assessed with greater sensitivity and specificity than when computed tomography (CT) is used. It seems to be certain that PET is useful for interim examinations too, in terms of assessing prognosis in DLBCL and HL, although its impact in terms of early changes to treatment is still to be determined. The criteria for interpreting the results of these early assessments are still evolving and the annual meetings in Menton, France, of groups of experts are leading towards a uniform interpretation method. In other types of lymphoma, PET can be useful for confirming local disease staging, especially in follicular lymphoma, and for guiding biopsy in patients with low-grade lymphoma that is suspicious for transformation into more aggressive disease. Several studies are in agreement that PET is valuable for assessing prognosis at treatment completion in FL and mantle cell lymphoma, but prospective studies are needed for this new indication to be validated.

FDG-PET in the evaluation of myeloma in 2012.

Multiple myeloma (MM) is a malignant haematological disease characterised by clonal proliferation of malignant plasma cells in the bone marrow. MM is expressed by diffuse infiltration of the bone marrow, focal bone lesions and extra-medullary lesions. Conventional staging follows the Salmon and Durie classification, which was recently revised (Salmon and Durie plus) to include MRI and FDG-PET examinations. FDG-PET is being evaluated for initial staging and therapeutic monitoring and its place still needs to be validated, particularly in comparison with MRI of the pelvis and spine, the reference examination for diagnosis, which is systematically combined with X-rays of the skeleton. Certain recent data in the literature suggest that FDG-PET provides better staging of the disease at the time of diagnosis than MRI, and that the examination has considerable prognostic value when it normalises after the initial courses of chemotherapy and at the end of treatment. As for the evaluation of lymphomas, the interpretation criteria should be standardised.

FDG-PET in Follicular Lymphoma Management.

18-Fluoro-deoxyglucose positron emission tomography/computerised tomography (FDG PET/CT) is commonly used in the management of patients with lymphomas and is recommended for both initial staging and response assessment after treatment in patients with diffuse large B-cell lymphoma and Hodgkin lymphoma. Despite the FDG avidity of follicular lymphoma (FL), FDG PET/CT is not yet applied in standard clinical practice for patients with FL. However, FDG PET/CT is more accurate than conventional imaging for initial staging, often prompting significant management change, and allows noninvasive characterization to guide assessment of high-grade transformation. For restaging, FDG PET/CT assists in distinguishing between scar tissue and viable tumors in residual masses and a positive PET after induction treatment would seem to predict a shorter progression-free survival.

Comparisons of dosimetric approaches for fractionated radioimmunotherapy of non-Hodgkin lymphoma.

AIM: The aim of this study was to compare different dosimetric approaches on therapy naïve patients enrolled in a multicentre fractionated radioimmunotherapy trial, to determine which methodological approach correlates with bone marrow toxicity. METHODS: Twenty-height non-Hodgkin lymphoma patients were treated with one or two fractions of 90Y-Ibritumomab-Tiuxetan (11.1 MBq/kg) 8 to 12 weeks apart in four different institutions. Quantitative imaging with 111In-Ibritumomab-Tiuxetan (185 MBq) was performed at 0, 1, 4 and 7 days after infusion, starting two weeks before the therapeutic administration. A whole-body (WB) CT scan was also acquired prior to the 111In-Ibritumomab injection, for attenuation correction purposes and was segmented to derive patient-specific organ masses. All dosimetry processing was centralized in a single institution. The first method (M_2D) was based on geometric mean WB scans, corrected for attenuation, scatter and organs superposition. The second method (M_2.5D) was based on the computed assisted matrix inversion approach and used segmented CT scans. The third method (M_3D) used iterative reconstruction of tomographic scans, corrected for attenuation, scatter and collimator response. Absorbed doses were estimated for lungs, liver, kidneys and spleen using MIRD S values adjusted for organ masses. Bone marrow (BM) absorbed doses were evaluated according to imaging methods (3) and compared to blood-based approaches. RESULTS: For some patients, organ masses such as liver or spleen significantly differed from male/female reference masses, whereas lungs and kidneys masses were relatively constant. Except for lungs, absorbed doses estimated by M_2D were higher than those from M_2.5D and these, in turn, were higher that those calculated from M_3D (Wilcoxon P<8.6e-4). Median organ absorbed dose estimates were equivalent for both fractions except for the spleen. In fact, spleen absorbed doses for the second fraction were lower than those for the first fraction, regardless of the approach. Possible explanations are that patient spleen masses were kept constant for analysis of both fractions and/or that spleen uptake was lowered after the first fraction. Estimation of BM absorbed doses from blood sampling was unable to predict platelet toxicity, but image-based methods performed better. Additionally, for most organs, the absorbed dose delivered by the first fraction could predict that delivered by the second fraction. CONCLUSION: These results confirm that different acquisition/processing protocols will lead to statistically different absorbed doses. Additionally, image-based dosimetric approaches are needed in order to correlate absorbed dose to bone marrow toxicity.

[Laparoscopic sentinel lymph node (SLN) dissection for clinically localized prostate carcinoma: results obtained in the first 70 patients]. / Détection laparoscopique des ganglions sentinelles dans le cancer localisé de la prostate: résultats obtenus chez 70 premiers patients.

OBJECTIVES: The lymph node metastasis is an important prognostic factor in prostatic cancer. The aim of this prospective study was to evaluate the relevance of the sentinel lymph node biopsy by laparoscopy in staging locoregional patients with clinically localized PC. PATIENTS AND METHODS: A transrectal ultrasound-guided injection by 0.3 mL/100 MBq (99m)Tc-sulfur rhenium colloid in each prostatic lobe was performed the day before surgery. The detection was realized intraoperatively with a laparoscopic probe (Clerad(®) Gamma Sup) followed by extensive dissection. Counts of SLN were performed in vivo and confirmed ex vivo. The histological analysis was performed by hematoxyline-phloxine-safran staining and followed by immunochemistry if SLN is free. RESULTS: Seventy patients with carcinoma of the prostate at intermediate or high risk of lymph node metastases were included. The intraoperative detection rate was 68/70 (97%). Fourteen patients had lymph node metastases, six only in SLN. The false negative rate was 2/14 (14%). The internal iliac region was the first metastatic site (40.9%). A metastatic sentinel node in common iliac region beyond the ureteral junction was present in 18.2%. A non-negligible sentinel metastatic region was the common iliac area (18.2%). Limited or standard lymph node dissection would have ignored respectively 72.7% and 59% of lymph node metastases. CONCLUSION: The laparoscopy is adapted to a broad identification of SLN and targeted dissection of these lymph nodes significantly limited the risk of surgical extended dissection while maintaining the accuracy of the information.

Clinical dosimetry in the treatment of bone tumors: old and new agents.

Treatment of multisite, sclerotic bone metastases is successfully performed by radionuclide therapy. Pain palliation is the most common aim for the treatment. Two radiopharmaceuticals are currently approved by the European Medicines Agency ((153)Sm-EDTMP and (89)Sr-Cl2) whilst other radiopharmaceuticals are at different stages of development, or are approved in some European countries ((186)Re-HEDP, (117)Snm-DTPA and (223)Ra-Cl2). The tissues at risk for the treatment are bone marrow and normal bone. A review of the methods applied for dosimetry for these tissues and for tumours is performed, including the calculation of S values (the absorbed dose per decay) and optimal procedures on how to obtain biodistribution data for each radiopharmaceutical. The dosimetry data can be used to individualise and further improve the treatment for each patient. Dosimetry for radionuclide therapy of bone metastases is feasible and can be performed in a routine clinical practice.

Impact of high-dose chemotherapy followed by auto-SCT for positive interim [18F] FDG-PET diffuse large B-cell lymphoma patients.

[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is increasingly used for response assessment in diffuse large B-cell lymphoma (DLBCL). A positive interim FDG-PET was shown to be associated with an unfavorable outcome in high-grade non-Hodgkin's lymphomas. For positive interim FDG-PET patients, the question of increasing the intensity of treatment using high-dose chemotherapy followed by auto-SCT (HDC-ASCT) remains unanswered. We retrospectively analyzed the prognostic value of FDG-PET in 42 DLBCL patients who were systematically evaluated at time of diagnosis, before and after HDC-ASCT. Of note, HDC-ASCT was part of the initial treatment strategy, while FDG-PET results did not influence the treatment approach. Results and outcome were analyzed according to FDG-PET results before and after HDC-ASCT. Patients were classified into three groups according to FDG-PET results before and after HDC-ASCT: those who were negative before and after (-/-; n=25), positive before and negative after (+/-; n=9) or positive before and after (+/+; n=8). The median follow-up was 34.5 (range, 19-74) months. The median EFS was significantly lower for the +/+ group (27.4 months) as compared with other groups (median not reached; P=0.0001). More importantly, there was no difference in term of EFS between the -/- group compared with the +/- group. These results suggest that HDC-ASCT can significantly improve the bad prognosis, otherwise indicated by a positive interim FDG-PET.

Preoperative localization of parathyroid lesions. Value of 99mTc-MIBI tomography and factors influencing detection.

UNLABELLED: The AIM of our study was to assess retrospectively the value of (99m)Tc-MIBI SPECT in the localization of parathyroid lesions in primary hyperparathyroidism and to determine the impact of PTH level, age, sex, characteristics of the lesions and thyroid nodules on the sensitivity of imaging. PATIENTS, METHODS: Fifty nine patients who were cured after the resection of 60 lesions (50 adenomas, 9 hyperplasias and 1 carcinoma, 9 of them in ectopy) were selected. (99m)TcO(4)(-), early and late (99m)Tc-MIBI planar images (n = 59), (99m)Tc-MIBI SPECT (n = 58) and ultrasound (n = 50) performed preoperatively were analyzed. The imaging results were compared to surgical and histological findings and correlated to different factors suspected of influencing the imaging's sensitivity. RESULTS: Sensitivity of double phase (99m)Tc-MIBI/(99m)TcO(4)(-) scintigraphy was higher than that of early or late scintigraphy alone. SPECT increased the sensitivity of scintigraphy from 85% to 92% and was useful to confirm doubtful foci and to localize ectopic lesions. Ultrasound (US) had the lowest sensitivity (56%) and the highest rate of false-positive results (n = 10), but identified 2 adenomas which were not detected by scintigraphy. Combining all imaging modalities, sensitivity reached 96%. Better sensitivities were observed when age <69 years, preoperative PTH level > or =155 pg/ml, weight of the gland > or =0.80 g and in the absence of thyroid nodules. US was more influenced by these factors than scintigraphy. CONCLUSION: Combination of US, double-phase (99m)Tc-MIBI/(99m)TcO(4)(-) planar scintigraphy and SPECT is the most accurate method for the detection of parathyroid lesions and should be performed before minimally invasive surgery, especially when PTH level is low, in older patients and in cases of multinodular goiter.

[Alpha-radioimmunotherapy: a review of recent developments]. / Le point sur les avancées récentes de la radio-immunothérapie alpha.

The use of heavy particles in the treatment of cancer is increasing remarkably, whether with external radiation or using a vector such as an antibody in radioimmunotherapy. Recent pre-clinical and clinical developments of alpha-radioimmunotherapy have provided more interesting information in parallel of the use of high Linear Energy Transfer (LET) external irradiation. This review aims at presenting recent advances of this therapeutic approach, and at detailing the biological specificities of this kind of radiation.

A rare gynecological case of paraneoplastic cerebellar degeneration discovered by FDG-PET.

BACKGROUND: PET/CT may be particularly useful to detect the primary cancer in paraneoplastic cerebellar degeneration (PCD) with anti-Yo which is most commonly associated with breast, ovarian and other gynecological cancers. CASE: A 60-year-old woman developed a PCD associated with anti-Yo antibodies in serum and cerebrospinal fluid. Conventional imaging was negative. FDG-PET showed an abnormal hot spot in the right ovarian area associated with lombo aortic lymph nodes. The diagnosis was confirmed by surgery as an ovarian adenocarcinoma. CONCLUSION: In this case report, FDG-PET played a crucial role in detecting the unknown primary tumor in a patient with PCD.

Current status and perspectives in alpha radioimmunotherapy.

Systemic administration of radiolabeled antibody directed against tumor antigens in radioimmunotherapy (RIT) enables to specifically target the cancer cells and to destroy them. So far, this strategy has proven its efficiency in the treatment of some hematological cancers with antibodies labeled with beta emitting radionuclides. In the last 2 decades, availability of short half life alpha emitters prompted to consider their use in RIT. Contrary to beta particles, alpha particles have a short path length and display a high lineic energy transfer. Those physical characteristics open new fields of clinical applications complementary to beta-RIT. To date, alpha-RIT is still at a preclinical stage of development: the radiolabeling methods need to be optimized to ensure in vivo stability of the radiopharmaceuticals. Some radionuclides have complex decay schemes with daughters emitting further alpha particles whose toxicity needs to be investigated. The modalities of administration of radiolabeled antibodies in animal models require also to be improved for delivering higher doses to tumor targets. A comprehensive analysis of the specific events occurring at cell or tissue level in response to alpha irradiation would be of great interest in order to define the best therapeutic association for residual disease or consolidation treatments. This approach has been proven to be efficient in increasing antitumor response either by using high doses with organ protection (kidney, bone marrow) or by a synergistic effect between alpha-RIT and associated treatments, such as chemotherapy.