Therapy-related myeloid neoplasm after peptide receptor radionuclide therapy (PRRT) in 1631 patients from our 20 years of experiences: prognostic parameters and overall survival.

PURPOSE: To determine prognostic factors and overall survival (OS) in therapy-related myeloid neoplasm (t-MN) of patients after receiving peptide receptor radionuclide therapy (PRRT). METHODS: All patients treated from February 1999 until September 2019 at our center who had bone marrow biopsy-proven t-MN after PRRT were included. Patient characteristics, laboratory results, and all tumor-directed therapies before t-MN diagnosis were collected. Cox regression analysis was performed to identify parameters associated with OS. Receiver operating characteristic (ROC) curve analysis was used to define cutoff values as well as sensitivity and specificity of the parameters. RESULTS: Out of 1631 patients treated with PRRT, 30 patients developed t-MN comprising myelodysplastic syndrome (MDS) in 23 patients (77%) and acute myeloid leukemia (AML) in 7 patients (23%). The median OS of t-MN patients was 13 months (range 9.1-16.9 months): 6 months for AML and 15 months for the MDS subgroup, respectively. Higher platelet level was a significant prognostic parameter for longer OS (hazard ratio (HR): 0.99, P < 0.05). Using ROC analysis, the best cutoff value for thrombocyte count was 183.5 Gpt/L, resulting in a sensitivity of 92.3% and a specificity of 50%. Other factors, such as hemoglobin level, did not show a significant correlation with OS. CONCLUSION: Even rarely occurred, the OS is gravely compromised in t-MN patients after PRRT, and even less in the AML subgroup (6 months). Higher platelet value was a significant prognostic parameter for longer OS in t-MN patients.

Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a measure of PRRT efficacy, and moreover to identify prognostic gene clusters in pretreatment blood that could be interpolated with relevant clinical features in order to define a biological index for the tumor and a predictive quotient for PRRT efficacy. METHODS: NET patients (n = 54), M: F 37:17, median age 66, bronchial: n = 13, GEP-NET: n = 35, CUP: n = 6 were treated with (177)Lu-based-PRRT (cumulative activity: 6.5-27.8 GBq, median 18.5). At baseline: 47/54 low-grade (G1/G2; bronchial typical/atypical), 31/49 (18)FDG positive and 39/54 progressive. Disease status was assessed by RECIST1.1. Transcripts were measured by real-time quantitative reverse transcription PCR (qRT-PCR) and multianalyte algorithmic analysis (NETest); CgA by enzyme-linked immunosorbent assay (ELISA). Gene cluster (GC) derivations: regulatory network, protein:protein interactome analyses. STATISTICAL ANALYSES: chi-square, non-parametric measurements, multiple regression, receiver operating characteristic and Kaplan-Meier survival. RESULTS: The disease control rate was 72 %. Median PFS was not achieved (follow-up: 1-33 months, median: 16). Only grading was associated with response (p < 0.01). At baseline, 94 % of patients were NETest-positive, while CgA was elevated in 59 %. NETest accurately (89 %, χ(2) = 27.4; p = 1.2 × 10(-7)) correlated with treatment response, while CgA was 24 % accurate. Gene cluster expression (growth-factor signalome and metabolome) had an AUC of 0.74 ± 0.08 (z-statistic = 2.92, p < 0.004) for predicting response (76 % accuracy). Combination with grading reached an AUC: 0.90 ± 0.07, irrespective of tumor origin. Circulating transcripts correlated accurately (94 %) with PRRT responders (SD+PR+CR; 97 %) vs. non-responders (91 %). CONCLUSIONS: Blood NET transcript levels and the predictive quotient (circulating gene clusters+grading) accurately predicted PRRT efficacy. CgA was non-informative.

Gene transcript analysis blood values correlate with 68Ga-DOTA-somatostatin analog (SSA) PET/CT imaging in neuroendocrine tumors and can define disease status.

PURPOSE: Precise determination of neuroendocrine tumor (NET) disease status and response to therapy remains a rate-limiting concern for disease management. This reflects limitations in biomarker specificity and resolution capacity of imaging. In order to evaluate biomarker precision and identify if combinatorial blood molecular markers and imaging could provide added diagnostic value, we assessed the concordance between (68)Ga-somatostatin analog (SSA) positron emission tomography (PET), circulating NET gene transcripts (NETest), chromogranin A (CgA), and Ki-67 in NETs. METHODS: We utilized two independent patient groups with positive (68)Ga-SSA PET: data set 1 ((68)Ga-SSA PETs undertaken for peptide receptor radionuclide therapy (PRRT), as primary or salvage treatment, n = 27) and data set 2 ((68)Ga-SSA PETs performed in patients referred for initial disease staging or restaging after various therapies, n = 22). We examined the maximum standardized uptake value (SUVmax), circulating gene transcripts, CgA levels, and baseline Ki-67. Regression analyses, generalized linear modeling, and receiver-operating characteristic (ROC) analyses were undertaken to determine the strength of the relationships. RESULTS: SUVmax measured in two centers were mathematically evaluated (regression modeling) and determined to be comparable. Of 49 patients, 47 (96 %) exhibited a positive NETest. Twenty-six (54 %) had elevated CgA (χ(2) = 20.1, p < 2.5×10(-6)). The majority (78 %) had Ki-67 < 20 %. Gene transcript scores were predictive of imaging with >95 % concordance and significantly correlated with SUVmax (R (2) = 0.31, root-mean-square error = 9.4). The genes MORF4L2 and somatostatin receptors SSTR1, 3, and 5 exhibited the highest correlation with SUVmax. Progressive disease was identified by elevated levels of a quotient of MORF4L2 expression and SUVmax [ROC-derived AUC (R (2) = 0.7, p < 0.05)]. No statistical relationship was identified between CgA and Ki-67 and no relationship with imaging parameters was evident. CONCLUSION: (68)Ga-SSA PET imaging parameters (SUVmax) correlated with a circulating NET transcript signature. Disease status could be predicted by an elevated quotient of gene expression (MORF4L2) and SUVmax. These observations provide the basis for further exploration of strategies that combine imaging parameters and disease-specific molecular data for the improvement of NET management.

[Neuroendocrine neoplasms of the breast]. / Neuroendokrine Neoplasien der Mamma.

Neuroendocrine neoplasms (NEN) of the breast are specific tumor entities. According to the literature up to 5% of breast neoplasms are malignant epithelial neoplasms of the breast. They are defined by a neuroendocrine (NE) architecture and cytology combined with an expression of the neuroendocrine vesicle markers chromogranin A and/or synaptophysin. The diagnosis is supplemented by the receptor status and the proliferative activity. According to the World Health Organization (WHO) classification of 2012 the following groups of NEN are distinguished: (1) invasive breast carcinoma with NE differentiation, (2) well-differentiated neuroendocrine tumor (NET) and (3) poorly differentiated small cell carcinoma (NEC). This review article focuses on (1) the definition and basic principles of diagnostics, (2) the history, nomenclature and WHO classification from 2003 and 2012, (3) the frequency of breast NEN, (4) the hereditary background and functional activity, (5) the expression of receptors and (6) the possible clinical implications. In addition, the first results of a retrospective single center study (n = 465 patients with breast cancer over a time period of 4 years) on the frequency of NEN of the breast at the Breast Center of the University Hospital Düsseldorf are presented. In this study a frequency of 4.5% of NEN was found based on a diagnostic cut-off of > 50% Chromogranin A and/or synaptophysin positive tumor cells.

[Hereditary syndromes of neuroendocrine tumours]. / Hereditäre Syndrome neuroendokriner Tumore.

Diffuse localised neuroendocrinal cells represent the largest population of endocrinally active cells and can degenerate to malignant neuroendocrine tumours (NET). In this review the most important hereditary syndromes that predispose for endocrine and neuroendocrine tumours are presented and discussed. NET occur mainly as sporadic tumours. Current investigations on the pathogenesis of sporadic neuroendocrine tumours have revealed a close relationship between hereditary and sporadic neuroendocrine tumours. In the course of hereditary syndromes, such as multiple endocrine neoplasia, endocrine and neuroendocrine tumours as well as non-endocrine neoplasias can occur. In order to recognise these syndromes in good time a knowledge of the predisposing syndromes and their cardinal symptoms is essential. In this way not only individualised diagnosis and therapy can be planned but also an appropriate early management of first degree relatives can be initiated.

[Pulmonary neuroendocrine neoplasms]. / Neuroendokrine Neoplasien der Lunge.

The pulmonary neuroendocrine neoplasms originate from the enterochromaffin cells which are diffusely distributed in the body. The incidence of these tumors has increased significantly in recent decades due to the available diagnostics. They make up about 1-2% of all lung tumors and 20-30% of all neuroendocrine neoplasms. The current WHO classification from 2004 divides them into typical carcinoids (TC), atypical carcinoids (AC), large cell neuroendocrine carcinomas (LCNEC) and small cell carcinomas (SCLC). The major neuroendocrine biomarkers are chromogranin A, synaptophysin and CD56. TC have a low mitotic rate of <2 mitoses/2mm(2) (10 HPF), whereas the mitotic rate of the AC is 2-10 mitoses/2 mm(2) (10 HPF). The Ki-67 staining is helpful to distinguish typical and atypical carcinoids from the highly malignant LCNEC and SCLC. Clinically, the patient presents usually with cough, hemoptysis or bronchial obstruction. The occurrence of a carcinoid or Cushing's syndrome and a tumor-associated acromegaly are rare. Surgical resection with radical lymph node dissection is the treatment of choice for achieving long-term survival. Endoscopic resection of the endobronchial tumor growth is a good alternative for inoperable endobronchially localized tumors. Peptide receptor radionuclide therapy (PRRT) is a promising treatment option for patients with metastatic or unresectable pulmonary neuroendocrine tumors. New targeted therapies using angiogenesis inhibitors, mTOR inhibitors, and tyrosine kinase inhibitors are being tested for their effectiveness in many previous studies. Typical carcinoid tumors metastasize less frequently than AC, the 5-year survival rate of patients with TC being over 90%. Patients with AC have a 5-year survival rate between 35% and 87%. The highly malignant LCNEC and SCLC, on the other hand, have a 5-year survival rate between 15% and 57%, and <5% respectively. The increasing number of therapeutic options and diagnostic procedures requires a multidisciplinary approach and decision-making in multidisciplinary tumor conferences to ensure a personalized treatment approach. Therefore patients with a neuroendocrine neoplasm of the lung should be treated in specialized centers.

The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours.

Peptide receptor radionuclide therapy (PRRNT) is a molecularly targeted radiation therapy involving the systemic administration of a radiolabelled peptide designed to target with high affinity and specificity receptors overexpressed on tumours. PRRNT employing the radiotagged somatostatin receptor agonists (90)Y-DOTATOC ([(90)Y-DOTA(0),Tyr(3)]-octreotide) or (177)Lu-DOTATATE ([(177)Lu-DOTA(0),Tyr(3),Thr(8)]-octreotide or [(177)Lu-DOTA(0),Tyr(3)]-octreotate) have been successfully used for the past 15 years to target metastatic or inoperable neuroendocrine tumours expressing the somatostatin receptor subtype 2. Accumulated evidence from clinical experience indicates that these tumours can be subjected to a high absorbed dose which leads to partial or complete objective responses in up to 30 % of treated patients. Survival analyses indicate that patients presenting with high tumour receptor expression at study entry and receiving (177)Lu-DOTATATE or (90)Y-DOTATOC treatment show significantly higher objective responses, leading to longer survival and improved quality of life. Side effects of PRRNT are typically seen in the kidneys and bone marrow. These, however, are usually mild provided adequate protective measures are undertaken. Despite the large body of evidence regarding efficacy and clinical safety, PRRNT is still considered an investigational treatment and its implementation must comply with national legislation, and ethical guidelines concerning human therapeutic investigations. This guidance was formulated based on recent literature and leading experts' opinions. It covers the rationale, indications and contraindications for PRRNT, assessment of treatment response and patient follow-up. This document is aimed at guiding nuclear medicine specialists in selecting likely candidates to receive PRRNT and to deliver the treatment in a safe and effective manner. This document is largely based on the book published through a joint international effort under the auspices of the Nuclear Medicine Section of the International Atomic Energy Agency.

Peptide receptor radionuclide therapy for neuroendocrine tumors in Germany: first results of a multi-institutional cancer registry.

Peptide receptor radionuclide therapy is an effective treatment option for patients with well-differentiated somatostatin receptor-expressing neuroendocrine tumors. However, published data result mainly from retrospective monocentric studies. We initiated a multi-institutional, prospective, board-reviewed registry for patients treated with peptide receptor radionuclide therapy in Germany in 2009. In five centers, 297 patients were registered. Primary tumors were mainly derived from pancreas (117/297) and small intestine (80/297), whereas 56 were of unknown primary. Most tumors were well differentiated with median Ki67 proliferation rate of 5% (range 0.9-70%). Peptide receptor radionuclide therapy was performed using mainly yttrium-90 and/or lutetium-177 as radionuclides in 1-8 cycles. Mean overall survival was estimated at 213 months with follow-up between 1 and 230 months after initial diagnosis, and 87 months with follow-up between 1 and 92 months after start of peptide receptor radionuclide therapy. Median overall survival was not yet reached. Subgroup analysis demonstrated that best results were obtained in neuroendocrine tumors with proliferation rate below 20%. Our results indicate that peptide receptor radionuclide therapy is an effective treatment for well- and moderately differentiated neuroendocrine tumors irrespective of previous therapies and should be regarded as one of the primary treatment options for patients with somatostatin receptor-expressing neuroendocrine tumors.

Pancreatic neuroendocrine neoplasms.

Pancreatic neuroendocrine tumors originate from the diffuse neuroendocrine system in the pancreatic region. These tumors exhibit a rising incidence despite their rareness and due to their benign behavior a considerable prevalence. Pathogenesis of pancreatic neuroendocrine tumors is characterized by common pathways of hereditary and sporadic tumors. Pancreatic neuroendocrine tumors may secrete peptide hormones or biogenic amines in an autonomous fashion as functional active tumors. Pathological grading and staging by TNM systems has been established in recent years classifying well and moderately differentiated pancreatice neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas. Chromogranin A and less so pancreatic polypeptide are suitable tumor markers for pancreatic neuroendocrine tumors. Expression of receptors for somatostatin is the basis of treatment of pancreatic neuroendocrine tumors with somatostatin analogues as antisecretive and antiproliferative agents. In addition, somatostatin scintigraphy or PET/CT allows comprehensive diagnosis of pancreatic neuroendocrine tumors, which should be supported by (endoscopic and contrast enhanced) ultrasound, CT and MRI. Therapy of pancreatic neuroendocrine tumors consists of somatostatin analogues, chemotherapy, targeted therapy and peptide receptor radionuclide therapy. Two molecular substances hav been registered for pancreatic neuroendocrine tumors recently, sunitinib (Sutent®) and everolimus (Afinitor®). Predominant tumor load in the liver may be treated by local ablative therapy or liver transplantation. These treatment options have been included in guidelines of several professional societies and weighted for sequential therapy of patients with pancreatic neuroendocrine tumors according to effects and side effects.

[Expert dialogue: neuroendocrine tumours of the lungs and gastroenteropancreatic system]. / Expertendialog: Neuroendokrine Tumore der Lunge und des gastroenteropankreatischen Systems.

BACKGROUND: Neuroendocrine tumours of the lung exhibit an increasing incidence and prevalence. However, data on the diagnosis of and therapy for these tumours are sparse compared to neuroendocrine tumours of the gastroenteropancreatic system. METHODS: The present article reflects a dialogue between experts on neuroendocrine tumors of the lung and the gastroenteropancreatic system held on February 25th and 26th in Weimar, Germany. RESULTS: Many similarities exist between neuroendocrine tumours of the lung and the gastroenteropancreatic system but there are also significant differences. Similarities exist mainly concerning pathology, diagnosis and therapy. Differences exist regarding the systemic therapy and the significantly lower incidence of paraneoplastic syndromes. Somatostatin receptor PET/CT with gallium-68 labelled somatostatin analogues and peptide receptor radiotherapy are innovative methods for the diagnosis of and therapy for neuroendocrine tumours of the lung. The first treatment option remains complete resection of the tumour. Small molecules like everolimus (Afinitor®) have been tested in clinical trials and have been shown to prolong progression-free survival. CONCLUSIONS: Additional studies are necessary and efforts should be undertaken to establish a registry to increase data on methods suitable for he diagnosis of and therapy for neuroendocrine tumours of the lung.

[Somatostatin receptor PET/CT (SSTR-PET/CT)]. / Somatostatinrezeptor-PET/CT.

The present guideline is focused on quality assurance of somatostatin receptor PET/CT (SSTR-PET/CT) in oncology patients. The document has been developed by a multidisciplinary board of specialists providing consensus of definitions, prerequisites, methodology, operating procedures, assessment, and standardized reporting. In particular, imaging procedures for the two most commonly used radioligands of human SSTR, i. e. 68Ga-DOTATOC and 68Ga-DOTATATE are presented. Overall, SSTR-PET/CT requires close interdisciplinary communication and cooperation of referring and executing medical disciplines, taking into account existing guidelines and recommendations of the European and German medical societies, including the European Association of Nuclear Medicine (EANM), German Society for Endocrinology (DGE), German Society for Nuclear Medicine (DGN) and German Society for Radiology (DRG).

Immunoscintigraphy of human mammary carcinoma xenografts using monoclonal antibodies 12H12 and BM-2 labeled with 99mTc and radioiodine.

For immunoscintigraphic localization of human breast cancer two monoclonal antibodies (mabs) 12H12 (immunoglobulin G1) and BM-2 (immunoglobulin G3) were developed. The mabs, directed against two different epitopes on the mucin glycoprotein TAG-12, showed reactivity with 96% of all primary mammary carcinomas. The antibodies were labeled with either 125I or 131I. In addition, 12H12 was directly labeled with 99mTc according to the method of Schwarz and Steinsträsser (A. Schwarz and A. Steinsträsser, J. Nucl. Med., 28:721, 1987). Biodistribution was measured in female nude mice bearing the human mammary carcinoma SF-15. Both radioiodinated mabs showed similar biodistribution with fast tumor uptake (8.5% injected dose/g at 6 h postinjection), which increased to 10-11% injected dose/g at 24 h and subsequently remained constant up to 120 h. 99mTc-Labeling of the mab 12H12 led to an enhanced tumor uptake of 10.5 and 14% injected dose/g at 6 and 24 h postinjection, respectively, and to significantly accelerated blood clearance of radioactivity. Similar results were obtained with a second mammary tumor (AR-1), while an endometrial tumor (EK-3) showed a 3-fold lower accumulation of radioactivity and no difference in uptake of radio-iodinated and 99mTc-labeled 12H12. Scintigraphic imaging of tumor-bearing nude mice with the 99mTc 12H12 at 24 h postinjection clearly demonstrated a diagnostic potential of the new mab for tumor localization and staging.

Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: A multi-institutional registry study with prospective follow-up.

BACKGROUND: Monocentric and retrospective studies indicate effectiveness of peptide receptor radionuclide therapy targeting somatostatin receptors of neuroendocrine neoplasms. We assessed overall and progression-free survival and adverse events of peptide receptor radionuclide therapy by a multi-institutional, board certified registry with prospective follow-up in five centres in Germany. METHODS: A total of 450 patients were included and followed for a mean of 24.4 months. Most patients had progressive low- or intermediate grade neuroendocrine neoplasms and 73% were pretreated with at least one therapy. Primary neuroendocrine neoplasms were mainly derived of pancreas (38%), small bowel (30%), unknown primary (19%) or bronchial system (4%). Patients were treated with Lutetium-177 in 54%, with Yttrium-90 in 17% and with both radionuclides in 29%. Overall and progression-free survival was determined with Kaplan-Meier curves and uni-variate log rank test Cox models. FINDINGS: Median overall survival of all patients was 59 (95% confidence interval [CI] 49-68.9) months. Overall survival was significantly inferior in the patients treated with Yttrium-90 solely (hazard ratio, 3.22; 95% CI, 1.83-5.64) compared to any peptide receptor radionuclide therapy with Lutetium-177. Grade II (hazard ratio, 2.06; 95% CI, 0.79-5.32) and grade III (hazard ratio, 4.22; 95% CI, 1.41-12.06) neuroendocrine neoplasms had significantly worse overall survival than grade I neuroendocrine neoplasms. Patients with small neuroendocrine neoplasms of small bowel had significantly increased survival (hazard ratio, 0.39; 95% CI, 0.18-0.87) compared to neuroendocrine neoplasms of other locations. Median progression-free survival was 41 (35.9-46.1) months and significantly inferior in patients treated with Yttrium solely (hazard ratio, 2.7; 95% CI, 1.71-4.55). Complete remission was observed in 5.6% of patients, 22.4% had a partial remission, 47.3% were stable and 4% were progressive as best response. Adverse events of bone marrow and kidney function higher than grade III occurred in 0.2-1.5% of patients. INTERPRETATION: These results indicate that peptide receptor radionuclide therapy is a highly effective therapy for patients with low to intermediate grade neuroendocrine neoplasms with minor adverse events.

[Peptide receptor radionuclide therapy for patients with somatostatin receptor expressing tumours. German Guideline (S1)]. / Peptidrezeptor-Radionuklidtherapie Somatostatinrezeptor-exprimierender Tumore. DGN-Leitlinie (S1).

This document describes the guideline for peptide receptor radionuclide therapy (PRRT) published by the German Society of Nuclear Medicine (DGN) and accepted by the Association of the Scientific Medical Societies in Germany (AWMF) to be included in the official AWMF Guideline Registry. These recommendations are a prerequisite for the quality management in the treatment of patients with somatostatin receptor expressing tumours using PRRT. They are aimed at guiding nuclear medicine specialists in selecting likely candidates to receive PRRT and to deliver the treatment in a safe and effective manner. The recommendations are based on an interdisciplinary consensus. The document contains background information and definitions and covers the rationale, indications and contraindications for PRRT. Essential topics are the requirements for institutions performing the therapy, e. g. presence of an expert for medical physics, intense cooperation with all colleagues involved in the treatment of a patient, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how treatment has to be carried out technically. Here, quality control and documentation of labelling are of great importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with the involved medical disciplines. Generally, the decision for PRRT should be undertaken within the framework of a multi-disciplinary tumour board.

Direct labeling of monoclonal antibodies with technetium-99m by photoactivation.

UNLABELLED: Direct radiolabeling methods currently rely on the addition of exogenous chemical reagents to create the necessary binding sites for 99mTc binding to monoclonal antibodies (MAbs). This work describes the use of ultraviolet (UV) light to facilitate photoactivation of MAbs for 99mTc radiolabeling. METHODS: The parameters of exposure wavelength and solution composition were investigated to provide a basis for further development. Based on these results, various murine MAbs and a chimeric MAb were photoactivated using a 300-nm (nominal) wavelength, eight-lamp (3.9 W each) photochemical reactor providing exposure for defined time periods. The MAb preparations were stored frozen and subsequently labeled by the addition of pertechnetate. For MAb-170, the photoactivated preparation was compared to a stannous ion reduced preparation by radiochemical (radiolabeling yield, serum stability cysteine challenge), biochemical (SDS-PAGE, IEF, SE-HPLC) and immunochemical (immunoreactivity) assays and biodistribution studies in mice. RESULTS: Photoactivation produced high radiolabeling yields for all the MAbs studied and MAb-170 produced comparable in vitro quality control profiles and in vivo biodistribution data. CONCLUSION: The use of this relatively simple, short and easily controlled photoactivation process for MAbs facilitates facile radiolabeling with 99mTc and provides an alternative to the direct chemical radiolabeling procedures.

Improvement of radiation treatment planning in squamous-cell head and neck cancer by immuno-SPECT.

UNLABELLED: Previous studies have shown high accuracy for immunoscintigraphy with 99mTc-MAb-174 in patients with squamous-cell carcinoma of the head and neck region compared to CT and MRI. We conducted a prospective study to determine if immunoscintigraphy provides additional diagnostic information for radiation treatment planning. METHODS: Radioimmunoscintigraphy (RIS) was performed on 40 patients (planar, whole-body, SPECT) with histologically confirmed squamous-cell carcinoma (30 primary tumors, 10 recurrences) after injection of the 99mTc (1.1 GBq) labeled monoclonal anti-squamous-cell cancer antibody 174H0.64 (murine IgG1). Results were combined with information obtained by clinical examination, sonography, panendoscopy and x-ray CT. The strategy for radiation treatment and the required treatment volumes were defined with and without immunoscintigraphical findings. RESULTS: Additional diagnostically relevant information from RIS was obtained from 10 patients (25%) with advanced tumors or recurrences. In three patients (7.5%), the treatment volume had to be extended. The therapeutic strategy for seven patients (17.5%) had to be changed due to the detection of metastatic disease beyond the head and neck region. RIS of patients with squamous-cell cancers of the head and neck region with 99mTcMAb-174H0.64 enabled the detection of tumors that were not depicted by other conventional diagnostic imaging procedures. CONCLUSION: The use of RIS in radiation treatment planning of advanced tumors of the head and neck region appears to yield important diagnostic information that may alter patient management.

Semiquantitative SPECT tumor uptake of technetium-99m-labeled anti-CEA monoclonal antibody in colorectal tumor.

UNLABELLED: Technetium-99m-BW431/26 images were compared to images of resected tumor specimens to evaluate the efficacy and accuracy of SPECT imaging of colorectal carcinoma. METHODS: Immunoscintigraphy with 99mTc-BW431/26 was performed on seven patients with colorectal carcinoma and one patient with a benign colorectal tumor. Accumulation of 99mTc-BW431/26 in the tumor was expressed as the tumor-to-normal tissue count ratio (SPECT T/N ratio) calculated by a region of interest method on the SPECT images obtained 24 hr after administration of 99mTc-BW431/26. All patients underwent research of the tumor immediately after 24-hr imaging, and the radioactivity in tumor specimen and normal tissue was measured to calculate the tissue T/N ratio. RESULTS: SPECT demonstrated definite increased tracer uptake by the tumor in all colorectal cancer patients. The benign lesion showed tracer uptake to a lesser extent. SPECT, however, failed to visualize a 10-mm lesion in a patient with familial adenomatous polyposis despite a tissue T/N ratio of 4.8, while autoradiography showed radioactivity uptake in the polyps. CONCLUSION: Although SPECT has limitations in detecting small lesions because of its limited spatial resolution, T/N ratios could be measured exactly by SPECT if the lesion is of a certain volume. SPECT imaging with 99mTc-BW431/26 can precisely evaluate tracer uptake in tumors and predict the efficacy of radioimmunotherapy in patients with colorectal cancer.