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In 1942, eighty years ago, Dr. Hertz first conducted radioiodine (RAI) diagnosis and therapy for thyroid disorders followed later by the successful treatment of thyroid cancer patients using RAI. In 2022, memorial 80 years later, alpha emitter astatine (

Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement. The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [177Lu]Lu-PSMA-617 and a follow-up of at least 6 months. Tumour burden in the bone was classified prior to RLT as follows: less than 6 lesions, 6–20 lesions, more than 20 lesions and diffuse involvement. The response rate was evaluated using changes of the prostate-specific antigen (PSA) after the first treatment cycle. Overall survival was calculated from the date of the first treatment. Haematological adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6–20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (p

To determine prognostic factors and overall survival (OS) in therapy-related myeloid neoplasm (t-MN) of patients after receiving peptide receptor radionuclide therapy (PRRT). 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. 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

Introduction The impact of prior therapies, especially chemotherapy, on overall survival (OS) in patients with castration-resistant prostate cancer (CRPC) receiving [177Lu]Lu-PSMA-617 therapy has been the subject of controversy. Therefore, WARMTH decided to plan a multicenter retrospective analysis (the “617 trial”) to evaluate response rate and OS as well as the impact of prior therapies on OS in more than 300 patients treated with 177Lu-PSMA-617. Materials and methods The data of 631 metastatic CRPC (mCRPC) patients from 11 different clinics were evaluated. According to the inclusion and exclusion criteria, all patients had to have received at least abiraterone or enzalutamide prior to [177Lu]Lu-PSMA-617 therapy. The patients were divided into three groups: patients who had received prior chemotherapy, patients who avoided chemotherapy, and patients for whom a chemotherapy was contraindicated. Results The analysis included the data of 416 patients, with a median age of 71.9 years. At the time of analysis, 87 patients (20,9%) were still alive. A total of 53.6% of patients had received both abiraterone and enzalutamide; 75.5% and 26.4% had a history of chemotherapy with docetaxel and cabazitaxel, respectively. A total of 20.4% had had Ra-223. The median OS was 11.1 months. Prior chemotherapy, the existence of bone and liver metastases, as well as Eastern Cooperative Oncology Group (ECOG) status, were significant prognosticators of worse overall survival in both univariate and multivariate analyses. Patients without any prior chemotherapy showed a significantly longer OS (14.6 months). The median OS in patients who received one or two lines of chemotherapy with docetaxel or docetaxel followed by cabazitaxel, respectively, was 10.9 months and 8.9 months. There was no difference in OS between patients who had not received chemotherapy and patients for whom chemotherapy was contraindicated. The other prior therapies did not have any significant impact on OS. Conclusion In the present multicenter analysis, chemotherapy-naïve mCRPC patients receiving [177Lu]Lu-PSMA-617 therapy had a significantly longer OS than patients with a history of chemotherapy. This remained independent in the multivariate analysis besides presence of bone and liver metastases as negative prognosticators for survival, whereas an ECOG of 0–1 is associated with a longer OS.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) is effective for metastatic/inoperable neuroendocrine tumors (NETs). Imaging response assessment is usually efficient subsequent to treatment completion. Blood biomarkers such as PRRT Predictive Quotient (PPQ) and NETest are effective in real-time. PPQ predicts PRRT efficacy, NETest monitors disease. We prospectively evaluated: 1) NETest as a surrogate biomarker for RECIST; 2) The correlation of NETest levels with PPQ prediction. METHODS: Three independent (177)Lu-PRRT-treated GEP-NET and lung cohorts (Meldola, Italy: n=72; Bad-Berka, Germany: n=44; Rotterdam, Netherlands: n=41). Treatment response: RECIST1.1 [Responder (stable, partial and complete response) vs Non-Responder]. Blood sampling: pre-PRRT, before each cycle and follow-up (2-12 months). PPQ (positive/negative) and NETest (0-100 score) by PCR. Stable≤40; progressive >40). CgA (ELISA) as comparator. Samples deidentified, measurement and analyses blinded. Kaplan-Meier survival and standard statistics. RESULTS: 122 of the 157 were evaluable. RECIST stabilization or response in 67%; 33% progressed. NETest significantly (p40 (progressive) vs stable (≤40) significantly correlated with mPFS (not reached vs. 10 months; HR 0.04 (95%CI: 0.02-0.07). PPQ response prediction was accurate in 118 (97%) with a 99% accurate positive and 93% accurate negative prediction. NETest significantly (p97%) with the pretreatment PPQ response predictor. CgA was non-informative.

Prostate-specific membrane antigen (PSMA) is expressed in most prostate cancers and can be identified by PSMA-ligand imaging, which has already become clinically accepted in several countries in- and outside Europe. PSMA-directed radioligand therapy (PSMA-RLT) with Lutetium-177 (177Lu-PSMA) is currently undergoing clinical validation. Retrospective observational data have documented favourable safety and striking clinical responses. Recent results from a prospective clinical trial (phase II) have been published confirming high response rates, low toxicity and reduction of pain in metastatic castration-resistant prostate cancer (mCRPC) patients who had progressed after conventional treatments. Such patients typically survive for periods less than 1.5 years. This has led some facilities to adopt compassionate or unproven use of this therapy, even in the absence of validation within a randomised-controlled trial. As a result, a consistent body of evidence exists to support efficacy and safety data of this treatment. The purpose of this guideline is to assist nuclear medicine specialists to deliver PSMA-RLT as an "unproven intervention in clinical practice", in accordance with the best currently available knowledge.

PURPOSE: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has impacted the management of patients with prostate cancer (PCa) in many parts of the world. PSMA-targeted endoradiotherapies are also being increasingly utilized and for these applications, the radiopharmaceutical distribution in normal organs is particularly important because it may limit the dose that can be delivered to tumors. In this study, we measured both interpatient and intrapatient variability of [(18)F]DCFPyL uptake in the most relevant normal organs. PROCEDURES: Baseline and 6-month follow-up PSMA-targeted [(18)F]DCFPyL PET/computed tomography (CT) scans from 39 patients with PCa were reviewed. Volumes of interest were manually drawn using the best visual approximation of the organ edge for both lacrimal glands, all four major salivary glands, the liver, the spleen, and both kidneys for all patients. The average SUV(mean), the COVs, and intraclass correlation coefficients (ICCs) across scans were calculated. Bland-Altman analyses were performed for all organs to derive repeatability coefficients (RCs). RESULTS: The liver demonstrated the lowest interpatient variability (13.0 and 16.6 % at baseline and follow-up, respectively), while the spleen demonstrated the largest interpatient variability (44.6 and 51.0 % at baseline and follow-up, respectively). The lowest intrapatient variability was found in the spleen (ICC 0.86) while the highest intrapatient variability was in the kidneys (ICCs 0.40–0.50). Bland-Altman analyses showed 95 % repeatability coefficients for mean uptake >40 % for multiple organs and were highest for the lacrimal glands, kidneys, and spleen. CONCLUSIONS: Normal organs demonstrate significant variability in uptake of the PSMA-targeted radiotracer [(18)F]DCFPyL. Depending on the organ, different contributions of interpatient and intrapatient factors affect the intrinsic variability. The RCs also vary significantly among the different organs were highest for the lacrimal glands, kidneys, and spleen. These findings may have important implications for the design of clinical protocols and personalized dosimetry for PSMA-targeted endoradiotherapies.

Purpose Gastrin-releasing peptide receptors (GRPR) represent attractive targets for tumor diagnosis and therapy because of their overexpression in major human cancers. Internalizing GRPR agonists were initially proposed for prolonged lesion retention, but a shift of paradigm to GRPR antagonists has recently been made. Surprisingly, radioantagonists, such as [Tc-99m]DB1 (Tc-99m-N-4'-DPhe(6),Leu-NHEt13]BBN(6-13)), displayed better pharmacokinetics than radioagonists, in addition to their higher inherent biosafety. We introduce here [Ga-68]SB3, a [Tc-99m]DB1 mimic-carrying, instead of the Tc-99m-binding tetraamine, the chelator DOTA for labeling with the PET radiometal Ga-68. Methods Competition binding assays of SB3 and [Ga-nat]SB3 were conducted against [I-125-Tyr(4)]BBN in PC-3 cell membranes. Blood samples collected 5 min postinjection (pi) of the [Ga-67]SB3 surrogate in mice were analyzed using high-performance liquid chromatography (HPLC) for degradation products. Likewise, biodistribution was performed after injection of [Ga-67]SB3 (37 kBq, 100 mu L, 10 pmol peptide) in severe combined immunodeficiency (SCID) mice bearing PC-3 xenografts. Eventually, [Ga-68]SB3 (283 +/- 91 MBq, 23 +/- 7 nmol) was injected into 17 patients with breast (8) and prostate (9) cancer. All patients had disseminated disease and had received previous therapies. PET/CT fusion images were acquired 60-115 min pi. Results SB3 and [Ga-nat]SB3 bound to the human GRPR with high affinity (IC50: 4.6 +/- 0.5 nM and 1.5 +/- 0.3 nM, respectively). [Ga-67]SB3 displayed good in vivo stability (>85 % intact at 5 min pi). [Ga-67]SB3 showed high, GRPR-specific and prolonged retention in PC-3 xenografts (33.1 +/- 3.9%ID/g at 1 h pi - 27.0 +/- 0.9%ID/g at 24 h pi), but much faster clearance from the GRPR-rich pancreas (a parts per thousand 160%ID/g at 1 h pi to

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 Lu-177-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 %, chi(2) = 27.4; p = 1.2 x 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.

The dose-limiting salivary gland toxicity of 225Ac-labelled PSMA for treatment of metastatic, castration-resistant prostate cancer remains unresolved. Suppressing the metabolism of the gland by intraparenchymal injections of botulinum toxin appears to be a promising method to reduce off-target uptake. A 68Ga-PSMA PET/CT scan performed 45 days after injection of 80 units of botulinum toxin A into the right parotid gland in a 63-year-old patient showed a decrease in the SUVmean in the right parotid gland of up to 64% as compared with baseline. This approach could be a significant breakthrough for radioprotection of the salivary glands during PSMA radioligand therapy.

Endocrine pancreatic tumors (EPTs) are a heterogeneous group of neoplasms with variable clinical and biological features and prognosis, ranging from very slow-growing tumors to highly aggressive and very malignant ones. As other neuroendocrine tumors, EPTs are characterized by the presence of neuroamine uptake mechanisms and/or peptide receptors at the cell membrane and these features constitute the basis of the clinical use of specific radiolabeled ligands, both for imaging and therapy. The more widespread use of hybrid machines, i.e., positron emission tomography/computed tomography (PET/CT), allows to perform imaging with high resolution and high diagnostic accuracy especially for small lesions, and to correlate anatomic location with function. The recent WHO recommendations for classification and prognostic factors help the selection of tracers likely to show a positive image on PET; therefore, tracers exploiting specific metabolic patterns ((18)F-DOPA and (11)C-5-HTP) or specific receptor expression ((68)Ga-DOTA-peptides) are suited to well-differentiated tumors, while the use of (18)F-FDG is preferred for poorly-differentiated neoplasms with high proliferative activity and loss of neuroendocrine features. In differentiated EPTs, (11)C-5-HTP performs better than (18)F-DOPA even though its use is hampered by its complex production and limited availability and experience; (68)Ga-peptides are indicated for all type of gastroenteropancreatic (GEP) neuroendocrine tumors, regardless of their functional activity. In addition, (68)Ga-DOTA-peptides play a distinctive role in planning peptide receptor radionuclide therapy.

The aim of the study was to compare sequential (177)Lu-DOTA-TATE planar scans ((177)Lu-DOTA-TATE) in patients with metastasized neuroendocrine tumours (NET) acquired during peptide receptor radionuclide therapy (PRRT) for dosimetry purposes with the pre-therapeutic (68)Ga-DOTA-TATE positron emission tomography (PET)/CT ((68)Ga-DOTA-TATE) maximum intensity projection (MIP) images obtained in the same patients concerning the sensitivity of the different methods.A total of 44 patients (59 ± 11 years old) with biopsy-proven NET underwent (68)Ga-DOTA-TATE and (177)Lu-DOTA-TATE imaging within 7.9 ± 7.5 days between the two examinations. (177)Lu-DOTA-TATE planar images were acquired at 0.5, 2, 24, 48 and 72 h post-injection; lesions were given a score from 0 to 4 depending on the uptake of the radiopharmaceutical (0 being lowest and 4 highest). The number of tumour lesions which were identified on (177)Lu-DOTA-TATE scans (in relation to the acquisition time after injection of the therapeutic dose as well as with regard to the body region) was compared to those detected on (68)Ga-DOTA-TATE studies obtained before PRRT.A total of 318 lesions were detected; 280 (88%) lesions were concordant. Among the discordant lesions, 29 were (68)Ga-DOTA-TATE positive and (177)Lu-DOTA-TATE negative, whereas 9 were (68)Ga-DOTA-TATE negative and (177)Lu-DOTA-TATE positive. The sensitivity, positive predictive value and accuracy for (177)Lu-DOTA-TATE as compared to (68)Ga-DOTA-TATE were 91, 97 and 88%, respectively. Significantly more lesions were seen on the delayed (72 h) (177)Lu-DOTA-TATE images (91%) as compared to the immediate (30 min) images (68%). The highest concordance was observed for bone metastases (97%) and the lowest for head/neck lesions (75%). Concordant lesions (n = 77; mean size 3.8 cm) were significantly larger than discordant lesions (n = 38; mean size 1.6 cm) (p0.05). No such significance was found for differences in maximum standardized uptake value (SUV(max)). However, concordant liver lesions with a score from 1 to 3 in the 72-h (177)Lu-DOTA-TATE scan had a lower SUV(max) (n = 23; mean 10.9) than those metastases with a score of 4 (n = 97; mean SUV(max) 18) (p0.05).Although (177)Lu-DOTA-TATE planar dosimetry scans exhibited a very good sensitivity for the detection of metastases, they failed to pick up 9% of lesions seen on the (68)Ga-DOTA-TATE PET/CT. Three-dimensional dosimetry using single photon emission computed tomography/CT could be applied to investigate this issue further. Delayed (72 h) images are most suitable for drawing regions of interest for dosimetric calculations.

To explore feasibility, tolerability, dosimetry and probable efficacy of intravenous endoradiotherapy with carrier-added 4-[(131)I]iodo-L-phenylalanine (c.a. (131)I-IPA) in refractory high-grade glioma.Two male patients (45 and 50 years), with long-standing, extensively pre-treated gliomas and evidence of progression underwent single intravenous injections of 2 and 4 GBq of c.a. (131)I-IPA, respectively. Tumour targeting was verified by (131)I-IPA single-photon emission computed tomography (SPECT). Metabolic and morphological changes indicative of tumour response were assessed by sequential [(18)F]fluoroethyltyrosine ((18)F-FET) positron emission tomography (PET) and contrast-enhanced magnetic resonance imaging (MRI) following therapy. Further monitoring included clinical state, safety laboratory, quality of life and dosimetry. Absorbed mean organ and whole-body doses were determined according to the Medical Internal Radiation Dose (MIRD) scheme using OLINDAEXM based on serial planar scintigraphy.Both patients tolerated the treatment well. No evidence of acute or delayed organ toxicity was observed. (131)I-IPA accumulated in the tumour recurrences identified by MRI/(18)F-FET. In patient 1, PET showed progressively decreasing maximum standardised uptake values (SUVmax) over 10 months, indicating metabolic response, paralleled by reduced contrast enhancement and tumour volume on MRI. Progression occurred 18 months after therapy. Treatment was repeated using 6.6 GBq of (131)I-IPA, to which no response was observed. Patient 2, followed-up for 3 months after therapy, showed stable disease on MRI and PET. Mean absorbed whole body doses ranged from 0.13 to 0.17 mSv/MBq, with the highest absorbed organ doses to kidneys, bladder and heart (0.86-1.23; 0.49-0.6 and 0.45-0.56 mSv/MBq).Systemic endoradiotherapy using up to 6.6 GBq of c.a.(131)I-IPA is not associated with clinically detectable toxicity. Measurable anti-tumour effects in gliomas were observed. (131)I-IPA warrants further evaluation as glioma therapy.

Neuroendokrine Neoplasien (NEN) sind eine morphologisch homogen erscheinende, biologisch und klinisch jedoch sehr heterogene Tumorgruppe. NEN konnen in jedem inneren Organ auftreten, am haufigsten sind sie jedoch in der Lunge und im gastroenteropankreatischen (GEP) System. Um die Diagnostik und Klassifikation der GEP-NEN zu vereinheitlichen und zu verbessern, wurden durch die European Neuroendocrine Tumor Society (ENETS) in den letzten 5 Jahren Leitlinien erarbeitet. Unter Berucksichtigung dieser Leitlinien wurde 2009 die TNM-Klassifikation der Union for International Cancer Control (UICC) vorgestellt. 2010 schlieslich folgte eine neue Klassifikation der GEP-NEN durch die Weltgesundheitsorganisation (WHO). Diese Ubersicht fasst die neue Klassifikation und morphologische Diagnostik der GEP-NEN zusammen. Auf dieser Basis ist eine ausgezeichnete Prognoseeinsschatzung der GEP-NEN moglich. Sie bestimmt die Auswahl der Bildgebung und der Behandlungsoptionen und sichert auserdem die Vergleichbarkeit von groseren Tumorkollektiven.

Somatostatin receptors (SSTR) are known for an overexpression in gastroenteropancreatic neuroendocrine tumours (GEP-NET). The aim of the present study was to find out if the receptor density predicted by the semi-quantitative parameters generated from the static positron emission tomography (PET/CT) correlated with the in vitro immunohistochemistry using a novel rabbit monoclonal anti-SSTR2A antibody (clone UMB-1) for specific SSTR2A immunohistochemistry and polyclonal antibodies for SSTR1 and 3–5. Overall 14 surgical specimens generated from 34 histologically documented GEP-NET patients were correlated with the preoperative 68Ga-DOTA-NOC PET/CT. Quantitative assessment of the receptor density was done using the immunoreactive score (IRS) of Remmele and Stegner; the additional 4-point IRS classification for immunohistochemistry and standardized uptake values (SUVmax and SUVmean) were used for PET/CT. The IRS for SSTR2A and SSTR5 correlated highly significant with the SUVmax on the PET/CT (p

The nested stromal epithelial tumor (NSET) of the liver is a rare tumor entity which is being reported in young girls. In our 16-year-old female patient, we have performed a liver transplantation (LTX) for a non-metastasizing non-resectable liver tumor. The patient was tumor free in the follow-up. At 28 months postoperatively, we detected lung metastases in the F18-FDG-PET/CT. The patient died 37 months after LTX from progressive pulmonary metastases. LTX should not have been generally recommended for NSET. Further statements about the value of LTX for NSET will be possible only after evaluation of the course of the disease in a larger number of transplanted patients.

The aim of this document is to provide general information about mIBG scintigraphy in cancer patients. The guidelines describe the mIBG scintigraphy protocol currently used in clinical routine, but do not include all existing procedures for neuroendocrine tumours. The guidelines should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary from one country to another and from one medical institution to another. The present guidelines have been prepared for nuclear medicine physicians and intend to offer assistance in optimizing the diagnostic information that can currently be obtained from mIBG scintigraphy. The corresponding guidelines of the Society of Nuclear Medicine (SNM) and the Dosimetry, Therapy and Paediatric Committee of the EANM have been taken into consideration, and partially integrated into this text. The same has been done with the most relevant literature on this topic, and the final result has been discussed within a group of distinguished experts.

This bi-centric study aimed to determine the role of receptor PET/CT using (68)Ga-DOTA-NOC in the detection of undiagnosed primary sites of neuroendocrine tumours (NETs) and to understand the molecular behaviour of the primarily undiagnosed tumours.Overall 59 patients (33 men and 26 women, age: 65 + or - 9 years) with documented NET and unknown primary were enrolled. PET/CT was performed after injection of approximately 100 MBq (46-260 MBq) of (68)Ga-DOTA-NOC. The maximum standardised uptake values (SUV(max)) were calculated and compared with SUV(max) in known pancreatic NET (pNET) and ileum/jejunum/duodenum (SI-NET). The results of PET/CT were also correlated with CT alone.In 35 of 59 patients (59%), (68)Ga-DOTA-NOC PET/CT localised the site of the primary: ileum/jejunum (14), pancreas (16), rectum/colon (2), lungs (2) and paraganglioma (1). CT alone (on retrospective analyses) confirmed the findings in 12 of 59 patients (20%). The mean SUV(max) of identified previously unknown pNET and SI-NET were 18.6 + or - 9.8 (range: 7.8-34.8) and 9.1 + or - 6.0 (range: 4.2-27.8), respectively. SUV(max) in patients with previously known pNET and SI-NET were 26.1 + or - 14.5 (range: 8.7-42.4) and 11.3 + or - 3.7 (range: 5.6-17.9). The SUV(max) of the unknown pNET and SI-NET were significantly lower (p0.05) as compared to the ones with known primary tumour sites; 19% of the patients had high-grade and 81% low-grade NET. Based on (68)Ga-DOTA-NOC receptor PET/CT, 6 of 59 patients were operated and the primary was removed (4 pancreatic, 1 ileal and 1 rectal tumour) resulting in a management change in approximately 10% of the patients. In the remaining 29 patients, because of the far advanced stage of the disease (due to distant metastases), the primary tumours were not operated. Additional histopathological sampling was available from one patient with bronchial carcinoid (through bronchoscopy).Our data indicate that (68)Ga-DOTA-NOC PET/CT is highly superior to (111)In-OctreoScan (39% detection rate for CUP according to the literature) and can play a major role in the management of patients with CUP-NET.

Die radioaktive Markierung spezifischer Peptide, die gezielt an Somatostatinrezeptoren auf neuroendokrinen Tumoren binden, ermoglicht eine interne Strahlentherapie, die unter weitgehender Schonung des gesunden Gewebes (strahlenexponiert wird im Wesentlichen nur die Niere und erheblich weniger das Knochenmark) und meist nur geringer Belastung des Patienten mehrfach durchgefuhrt wird. Die Radiorezeptortherapie eignet sich besonders fur Patienten mit langsam wachsenden hepatischen und extrahepatischen Metastasen bzw. Tumoren, die erfahrungsgemas fur eine Chemotherapie weniger geeignet und bei denen die chirurgischen Moglichkeiten der Tumorresektion erschopft sind. Auch Patienten, die einen Progress der Erkrankung unter Octreotidtherapie bzw. kombinierter Biotherapie aufweisen, und solche mit ausgepragter klinischer Symptomatik trotz hoch dosierter Hormontherapie kommen fur eine Radiorezeptortherapie in Betracht. Die Behandlungsergebnisse der PRRT aus verschiedenen europaischen Zentren sowie von Multizenterstudien zeigen eine hohe Tumoransprechrate und einen signifikant positiven Effekt auf die klinische Symptomatik.

The aims of this study were to investigate the detection of cervical lymph node metastases of head and neck cancer by positron emission tomographic (PET) imaging with fluorine-18 fluorodeoxyglucose (FDG) and to perform a prospective comparison with computed tomography (CT), magnetic resonance imaging (MRI), sonographic and histopathological findings. Sixty patients with histologically proven squamous cell carcinoma were studied by PET imaging before surgery. Preoperative endoscopy (including biopsy), CT, MRI and sonography of the cervical region were performed in all patients within 2 weeks preceding 18F-FDG whole-body PET. FDG PET images were analysed visually and quantitatively for objective assessment of regional tracer uptake. Histopathology of the resected neck specimens revealed a total of 1284 lymph nodes, 117 of which showed metastatic involvement. Based on histopathological findings, FDG PET correctly identified lymph node metastases with a sensitivity of 90% and a specificity of 94% (P10(-6)). CT and MRI visualized histologically proven lymph node metastases with a sensitivity of 82% (specificity 85%) and 80% (specificity 79%), respectively (P10(-6)). Sonography revealed a sensitivity of 72% (P10(-6)). The comparison of 18F-FDG PET with conventional imaging modalities demonstrated statistically significant correlations (PET vs CT, P = 0.017; PET vs MRI, P = 0.012; PET vs sonography, P = 0.0001). Quantitative analysis of FDG uptake in lymph node metastases using body weight-based standardized uptake values (SUVBW) showed no significant correlation between FDG uptake (3.7+/-2.0) and histological grading of tumour-involved lymph nodes (P = 0.9). Interestingly, benign lymph nodes had increased FDG uptake as a result of inflammatory reactions (SUVBW-range: 2-15.8). This prospective, histopathologically controlled study confirms FDG PET as the procedure with the highest sensitivity and specificity for detecting lymph node metastases of head and neck cancer and has become a routine method in our University Medical Center. Furthermore, the optimal diagnostic modality may be a fusion image showing the increased metabolism of the tumour and the anatomical localization.

Hintergrund Eine exakte Ausbreitungsdiagnostik ist Voraussetzung fur die individualisierte Bestrahlungsplanung bei Patienten mit Kopf-Hals-Tumoren. Trotz hoher Zuverlassigkeit der in der Routine eingesetzten Verfahren Computer-und Kernspintomographie ist die sichere Diagnostik eines lymphonodalen Tumorbefalls oft nicht moglich. Wir untersuchten im Rahmen einer Studie, ob die zusatzliche Durchfuhrung einer18F-Fluordeoxyglucose-Positronenemissionstomographie (FDG-PET) hier einen fur die Radiotherapieplanung relevanten Informationsgewinn erbringt.

Intravenous injection of the murine monoclonal anti-CA125 antibody B43.13 (Ovarex: Ab1) into ovarian cancer patients led to the induction of an idiotypic network. Of the 75 patients who received one to ten injections of a 2-mg dose of the antibody, 48 developed anti-(mAb B43.13) antibodies (Ab2); 18 of these patients also had elevated levels of anti-[anti-(mAb B43.13)] antibodies (Ab3; = anti-CA125 antibodies) compared to pre-injection values. Characterization of these antibodies revealed that the binding to CA125 could be inhibited by mAb B43.13 in most samples. Human anti-CA125 antibodies or Ab3 purified from patient serum samples specifically recognized human ovarian tumor cells and tissues expressing CA125. In addition, these anti-CA125 antibodies were able to conduct Fc-mediated tumor cell killing (antibody-dependent cell-mediated cytotoxicity). This raises the possibility of using an Ab1 for anti-idiotype induction immunotherapy of cancer.

BACKGROUND [111In-DTPA-D-Phe1]-pentetreotide scintigraphy is able to detect neuroendocrine tumors not shown by radiological methods. PATIENTS AND METHODS In 270 patients with neuroendocrine gastroenteropancreatic tumors (GEP tumors) 400 somatostatin receptor scintigraphies were performed. 70 patients (38 female, 32 male, aged 28 to 74 [56 +/- 12.6] years) underwent surgery and follow-up over 2 years. The aim of the present study was the comparison of preoperative somatostatin receptor scintigraphy with radiological methods (sonography, CT) and intraoperative localization of GEP tumors with a hand-held gamma-probe. RESULTS Somatostatin receptor scintigraphy was successful in localizing primary tumors in all patients. Liver- and lymph node metastases could be visualized with a sensitivity of 94 and 95 percent. In 7 patients 35 lesions could be identified by intraoperative tumor localization using a hand held gamma probe. Radiological methods identified only 11, surgical palpation 15 and preoperative somatostatin receptor scintigraphy 27 lesions. CONCLUSION Somatostatin receptor scintigraphy improves detection of small and occult GEP tumors. Intraoperative probe counting with a hand-held gamma probe can identify tumors even when they are small and impalpable, but receptor positive.

This study presents immunoscintigraphic results in 24 patients suffering from primary colorectal cancer, recurrent or metastatic disease after the injection of 1197-1351 MBq technetium-99m labelled totally human monoclonal antibody 88BV59. Labelling efficacy of 99mTc-88BV59 ranged from 97% to 99%. Immunoscintigraphy was performed 18-20 h after injection. Scintigraphic findings were compared with those of computed tomography (CT). Patients underwent surgery in order to evaluate immunoscintigraphic findings histologically. Sera of the patients (before injection and 1 and 3 months post infusion) were analysed for the presence of human anti-human antibodies (HAHA). None of the patients showed a HAHA response as assessed by a solid-phase ELISA assay. The antibody scan detected about 25% more lesions than CT. In the detection of extrahepatic disease, the sensitivity of the antibody scan proved to be 68%, whereas the sensitivity of CT was 41%.

The lifetime risk of ovarian cancer has been estimated to be 1.4% (1 in 70 women), with a 5-year survival rate for all stages of 52% compared with 95% if diagnosed and treated while the disease is still localised.[4] Owing to the poorly defined symptom profile of ovarian cancer, approximately 70% of women are diagnosed with ovarian cancer at stages III and IV with an associated 5-year survival rate of 15–20% and 70% of patients relapse within 6–24 months of second-line treatment,[6] suggesting there is a need for further treatment options. Oregovomab (OvaRex®1) is an immunotherapeutic monoclonal antibody (MAb) with high affinity for the ovarian tumour-associated antigen, cancer 125 (CA125).[1] CA125 is shed from ovarian cancer cells and is elevated in 50% and 80% of patients with stage I and late-stage epithelial ovarian cancer, respectively.[4] Oregovomab induces broad humoral and cellular responses against CA125,[1] and is currently being evaluated as a treatment for patients with late-stage ovarian cancer after completion of first-line therapy. In patients in remission with biochemical relapse, the median time to relapse was greater in oregovomab recipients with an immune response than in nonresponders (35.3 vs 7.5 weeks; p = 0.0011) in a double-blind, placebo-controlled study.[7] A similar study in patients without biochemical relapse also reported that median time to relapse was greater in oregovomab recipients with an immune response than in those who did not respond (13.4 vs 4.7 months; p < 0.0001).[8] In a preliminary integrated analysis of two noncomparative trials in patients in relapse, the median time to disease progression was greater in oregovomab-treated patients with an immune response than in nonresponders (60.0 vs 10.7 weeks; p = 0.0026).[9] The tolerability profile of oregovomab is similar to that of placebo[8] with no treatment-related toxicity reported.[10]

Amyloidosis is a systemic disease frequently involving the myocardium and leading to functional disturbances of the heart. Amyloidosis can mimic other cardiac diseases. A conclusive clinical diagnosis of cardiac involvement can only be made by a combination of different diagnostic methods. In 7 patients with myocardial amyloidosis we used a combined first-pass and static scintigraphy with technetium-99 m-pyrophosphate. There was only insignificant myocardial uptake of the tracer. The first-pass studies however revealed reduced systolic function in 4/7 patients and impaired diastolic function in 6/7 patients. Therefore, although cardiac amyloid could not be demonstrated in the static scintigraphy due to amyloid fibril amount and composition, myocardial functional abnormalities were seen in the first-pass study.

Six European nuclear medicine centres per formed immunoscintigraphy first retrospectively in 34 patients using indium-111-labelled carcinoembryonic antigen (CEA)-specific and/or 19-9 F(ab')2 fragments. Results for sensitivity and specificity in tumour sites were 94% and 87%, respectively, for the pelvis and 73% and 100% for the extrahepatic abdomen. A second prospective series concerned 58 other patients previously operated on for colorectal adenocarcinoma (27 colon, 31 rectum). Two-thirds of these patients had a suspected recurrence signalled by an isolated rise in tumour markers, and 46 patients examined by immunoscintigraphy, X-ray computed tomography and ultrasonography were found to have a recurrence (a total of 62 tumour sites). Sensitivity and specificity with immunoscintigraphy were 90% and 97%, respectively, for the pelvis and 62% and 95% for the extrahepatic abdomen. For 29 patients injected with CEA-specific fragments, sensitivity was 90% and specificity 94% for the pelvis. For 25 patients injected with 19-9 fragments, pelvic sensitivity and specificity were 80% and 100%, respectively, whereas sensitivity for the extrahepatic abdomen was only 29% since several cases of peritoneal carcinosis were not visualized. In the prospective series, comparison of the three imaging techniques for all tumour sites (including liver and in 5 cases thorax) gave a sensitivity and specificity of 82% and 91 %, respectively, for immunoscintigraphy, 52% and 95% for X-ray computed tomography and 59% and 100% for ultrasonography. These results thus confirm the advantage of using111In-labelled CEA-specific or 19-9 to visualize and localize recurrences of colorectal cancer.

Die Somatostatinrezeptorszintigraphie (SMRS) dient dem spezifischen Nachweis neuroendokriner Tumoren (NET) sowie Rezeptor-positiver Metastasen mit hoher Sensitivitat (80–>95%) und ermoglicht eine Ganzkorperdiagnostik in einem Untersuchungsgang. Auch kleine Primartumoren und Metastasen, die mit CT, MRT und Sonographie nicht oder nur schwer nachweisbar sind, konnen bei hoher Rezeptorexpression szintigraphisch detektiert werden. Die SMRS sollte bei substanziellem Verdacht auf einen GEP-Tumor oder nach dem immunhistochemischen Nachweis eines NET als primares diagnostisches Verfahren vor CT und MRT zum Staging eingesetzt werden. Weitere Indikationen sind Verlaufskontrolle nach Operation, Rezidivdiagnostik bei Tumormarkeranstieg, Beurteilung des Ansprechens auf eine Chemotherapie oder biologische Therapie sowie die Differenzialdiagnose NET vs. nicht endokriner Tumor bei Nachweis einer Raumforderung, sofern eine bioptische Klarung nicht moglich ist. Letzlich ist die SMRS fur die Indikationsstellung zur Radiorezeptortherapie (Intensitat der Rezeptorexpression) sowie zur Verlaufskontrolle von essenzieller Bedeutung.

The aim of this document is to provide general information about 67Ga scintigraphy in oncology. These guidelines should not be taken as definitive for all possible 67Ga procedures or exclusive of other nuclear medicine procedures useful to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary from one country to another and from one medical institution to another. The present guide has been prepared for nuclear medicine physicians and is intended to offer assistance in optimising the diagnostic information that can be obtained from 67Ga scintigraphy. The existing guidelines of the Society of Nuclear Medicine (SNM) have been reviewed and integrated into the present text. The same has been done with the most relevant literature on this topic, and the final result has been discussed by a group of distinguished experts.

We report here on a new and quick procedure to isolate human (hu) CEA mouse anti CEA immune complexes of sera from patients admitted for immunoscintigraphy with radiolabeled monoclonal anti CEA antibody. This method employs rabbit anti mouse IgG immune affinity chromatography together with a commercial CEA-IRMA kit for the specific isolation of immune complexes. By applying this procedure we were able to show that immune complex formation increased in parallel to CEA serum concentration. The formation of immune complexes did not significantly affect tumor detection by immunoscintigraphy.