To assess the influence of sentinel lymph nodes (SNs) SPECT/CT and 18 F-choline (18 F-FCH) PET/CT in radiotherapy (RT) treatment planning for prostate cancer patients with a high-risk for lymph node (LN) involvement. Twenty high-risk prostate cancer patients underwent a pelvic SPECT acquisition following a transrectal ultrasound guided injection of 99mTc-Nanocoll into the prostate. In all patients but one an 18 F-FCH PET/CT for RT treatment planning was performed. SPECT studies were coregistered with the respective abdominal CTs. Pelvic SNs localized on SPECT/CT and LN metastases detected by 18 F-FCH PET/CT were compared to standard pelvic clinical target volumes (CTV). A total of 104 pelvic SNs were identified on SPECT/CT (mean 5.2 SNs/patient; range 1–10). Twenty-seven SNs were located outside the standard pelvic CTV, 17 in the proximal common iliac and retroperitoneal regions above S1, 9 in the pararectal fat and 1 in the inguinal region. SPECT/CT succeeded to optimize the definition of the CTV and treatment plans in 6/20 patients due to the presence of pararectal SNs located outside the standard treatment volume. 18 F-FCH PET/CT identified abnormal tracer uptake in the iliac LN region in 2/19 patients. These abnormal LNs were negative on SPECT/CT suggesting a potential blockade of lymphatic drainage by metastatic LNs with a high tumour burden. Multimodality imaging which combines SPECT/CT prostate lymphoscintigraphy and 18 F-FCH PET/CT identified SNs outside standard pelvic CTVs or highly suspicious pelvic LNs in 40% of high-risk prostate cancer patients, highlighting the potential impact of this approach in RT treatment planning.
Purpose: Peptide receptor radionuclide therapy (PRRT) delivers high absorbed doses to kidneys and may lead to permanent nephropathy. Reliable dosimetry of kidneys is thus critical for safe and effective PRRT. The aim of this work was to assess the feasibility of planning PRRT based on 3D radiobiological dosimetry (3D‐RD) in order to optimize both the amount of activity to administer and the fractionation scheme, while limiting the absorbed dose and the biological effective dose (BED) to the renal cortex. Methods: Planar and SPECT data were available for a patient examined with 111 In‐DTPA‐octreotide at 0.5 (planar only), 4, 24, and 48 h post‐injection. Absorbed dose and BED distributions were calculated for common therapeutic radionuclides, i.e., 111 In, 90 Y and 177 Lu, using the 3D‐RD methodology. Dose‐volume histograms were computed and mean absorbed doses to kidneys, renal cortices, and medullae were compared with results obtained using the MIRD schema (S‐values) with the multiregion kidney dosimetry model. Two different treatment planning approaches based on (1) the fixed absorbed dose to the cortex and (2) the fixed BED to the cortex were then considered to optimize the activity to administer by varying the number of fractions. Results: Mean absorbed doses calculated with 3D‐RD were in good agreement with those obtained with S‐value‐based SPECT dosimetry for 90 Y and 177 Lu. Nevertheless, for 111 In, differences of 14% and 22% were found for the whole kidneys and the cortex, respectively. Moreover, the authors found that planar‐based dosimetry systematically underestimates the absorbed dose in comparison with SPECT‐based methods, up to 32%. Regarding the 3D‐RD‐based treatment planning using a fixed BED constraint to the renal cortex, the optimal number of fractions was found to be 3 or 4, depending on the radionuclide administered and the value of the fixed BED. Cumulative activities obtained using the proposed simulated treatment planning are compatible with real activities administered to patients in PRRT. Conclusions: The 3D‐RD treatment planning approach based on the fixed BED was found to be the method of choice for clinical implementation in PRRT by providing realistic activity to administer and number of cycles. While dividing the activity in several cycles is important to reduce renal toxicity, the clinical outcome of fractionated PRRT should be investigated in the future.
During the selection of monoclonal antibodies (MAb) raised against purified carcinoembryonic antigen (CEA), two MAbs were identified which immunoprecipitated a glycoprotein of 95 kD present both in perchloric acid extracts of normal lung and on the surface of normal granulocytes. This antigen was distinct from the previously reported normal glycoprotein crossreacting with CEA (NCA) which had a molecular weight of 55 kD. The difference between the smaller and the larger crossreacting antigens termed NCA-55 and NCA-95, respectively, was demonstrated by SDS-polyacrylamide gel electrophoresis, by elution from Sephadex-G200 and by selective binding to a series of anti-CEA MAb. Out of six MAb which all bound CEA purified from colon carcinoma, three did not react with these two crossreacting antigens, one bound only NCA-95, one reacted only with NCA-55 and one reacted with both NCA-55 and NCA-95. Immunoadsorbent purified preparations of 125I labelled NCA-95 and NCA-55 were found useful for the screening of new anti-CEA MAb. In addition, when tested on frozen sections of colon carcinoma, normal spleen, normal lung and pancreas, each type of MAb gave a clearly different pattern of reactivity. The three anti-CEA MAb which did not bind any of the crossreacting antigens stained only the colon carcinoma cells; the MAb binding to either one of the two types of NCA gave a similar pattern of reactivity both on colon carcinoma cells and on granulocytes. However, on normal lung and pancreas, the MAb binding NCA-55 stained granulocytes as well as bronchiolar and alveolar epithelial cells in lung and inter- and intra-lobular duct epithelial cells in pancreas, whereas the MAb binding only NCA-95 stained only the granulocytes. Thus, the newly identified NCA-95 appears to differ from NCA-55 not only in terms of molecular size and antigenicity but also by the fact that in normal lung and pancreas it is found in granulocytes but not in epithelial cells.
A new method of thermoablation with hot water vapour based on a new type of microtube was developed. This approach allows tumours, with volume and anatomical positions not accessible to other techniques (cryoablation, radiofrequency ablation, laser ablation) to be treated.The method was tested on a human colon carcinoma grafted subcutaneously in Swiss nude mice and the experiment monitored under magnetic resonance imaging.It was found that 2.52 cal s(-1) per cm3 of tumour were necessary to reduce tumour size. The microtube is built to withstand a large range of temperatures and pressures and is biocompatible.A specific feature of this technique is that, besides hot vapour, several types of drugs can be delivered through the same microtube depending of the location, type or size of the tumour. These properties make it a unique device for multi-therapeutic treatments.
The study aim was to assess the safety, biodistribution, tissue kinetics, and tumor uptake of the (99m)Tc-labeled neurotensin (NT) analog NT-XI.Four patients presenting ductal pancreatic adenocarcinoma were studied with (99m)Tc-NT-XI. Patients were followed by scintigraphy up to 4 h and by continued blood and urinary sampling until surgery 18-22 h after injection. Surgical tissue samples were analyzed for radioactivity uptake and NT receptor expression.No side effects were observed on injection of (99m)Tc-NT-XI. Blood biologic half-lives alpha and beta were 35 min (range, 17-62 min) and 230 min (range, 107-383 min), respectively. Repeated whole-body scintigraphy performed in 2 patients showed a single exponential decrease of whole-body activity with half-lives of 101 and 232 min. Tracer elimination was mainly renal, with 92% and 98% of activity counted in urine in the first 20 h. Kidney, liver, spleen, and bone marrow activity uptake was observed in all patients. Tumor was not visualized in the first 3 patients but could be localized by tomoscintigraphy in the pancreas head region of patient 4. In vitro tissue analysis showed high expression of NT receptor in the tumor of patient 4, correlated with the highest tumor radioactivity uptake and the highest tumor-to-fat radioactivity ratio. In vitro receptor expression was also positive in a second patient having a tumor characterized by very low cellularity; however, the remaining 2 tumors lacked NT receptor expression.Injection of (99m)Tc-NT-XI was well tolerated. The in vivo tumor uptake appeared specific as it was observed in the 1 patient with a pancreatic tumor that expressed high amounts of NT receptor. The results are compatible with preclinical animal results and in favor of further development of radiolabeled NT analogs for diagnosis or therapy of cancer.
Recombinant vaccinia virus with tumour cell specificity may provide a versatile tool either for direct lysis of cancer cells or for the targeted transfer of genes encoding immunomodulatory molecules. We report the expression of a single chain antibody on the surface of extracellular enveloped vaccinia virus. The wild-type haemagglutinin, an envelope glycoprotein which is not required for viral infection and replication, was replaced by haemagglutinin fusion molecules carrying a single chain antibody directed against the tumour-associated antigen ErbB2. ErbB2 is an epidermal growth factor receptor-related tyrosine kinase overexpressed in a high percentage of human adenocarcinomas. Two fusion proteins carrying the single chain antibody at different NH2-terminal positions were expressed and exposed at the envelope of the corresponding recombinant viruses. The construct containing the antibody at the site of the immunoglobulin-like loop of the haemagglutinin was able to bind solubilized ErbB2. This is the first report of replacement of a vaccinia virus envelope protein by a specific recognition structure and represents a first step towards modifying the host cell tropism of the virus.
