[Procedure guidelines for radioiodine therapy of differentiated thyroid cancer. Version 4]. / Radioiodtherapie beim differenzierten Schilddrüsenkarzinom. Verfahrensanweisung - Version 4 (Stand 30.10.2015).

The procedure guideline for radioiodine therapy of differentiated thyroid cancer (version 4) was developed in the consensus of a representative expert group. This fulfils the level S1 (first step) within the AWMF classification of Clinical Practice Guidelines (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, Germany). This procedure guideline completed the guideline for surgical management of thyroid cancer (level S2) with the aspects from nuclear medicine. Controversies over ablative radioiodine therapy in small papillary thyroid cancers and in minimally invasive follicular cancer without angioinvasion, over empirical standard doses for ablative radioiodine therapy, and over the kind of TSH-stimulation were described and the guideline formulated a corridor of good clinical practice. The text has included the recent results from the National Cancer database and the SEER database (both from the USA), indicating that the ablative radioiodine therapy has improved the survival rate even in low risk patients. Such a statistically significant benefit can be detected only by a national cancer registry with long-term follow-up data.

Lacrimal Glands May Represent Organs at Risk for Radionuclide Therapy of Prostate Cancer with [(177)Lu]DKFZ-PSMA-617.

PURPOSE: Calculating the absorbed dose is important for the determination of risk and therapeutic benefit of internal radiation therapy. The aim of this study was to perform image-based absorbed dose calculation for critical organs during the first cycle of [(177)Lu]DKFZ-PSMA-617 therapy in a small cohort of patients with metastatic prostate cancer. PROCEDURES: Nine patients with a history of prostate cancer documented by histopathology and radiologic evidence of metastatic diseases underwent radioligand therapy with [(177)Lu]DKFZ-PSMA-617. Conjugated planar whole-body scintigraphies acquired at 0.5, 24, 48, 72, and 168 h post-injection were analyzed by regions of interest, and time-activity curves were generated for various organs. Cumulated activities and residence times were calculated by bi-exponential fit of the time-activity curves. Mean absorbed doses were finally estimated using OLINDA/EXM1.1™. Additionally, the uncertainty when omitting the last measurement (168 h p.i.) was studied. RESULTS: The following mean absorbed doses were calculated: 2.82 mGy/MBq for the lacrimal glands, 0.72 mGy/MBq for the salivary glands, 0.53 mGy/MBq for the kidneys, and 0.42 mGy/MBq for the nasal mucous membrane. Omitting the last measurement resulted in a mean deviation of 10 to 25 % for absorbed dose values as compared to the ones received by analyzing all measurements. CONCLUSION: Absorbed organ doses of [(177)Lu]DKFZ-PSMA-617 therapy are not likely to be critical for kidneys, salivary glands, and the nasal mucous membrane. The lacrimal glands may represent the dose-limiting organs. Whole-body scintigraphy appears sufficient for dose estimation, but late measurements are mandatory, if accurate dose calculation is required.

FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0.

The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.

Inferring primary tumor sites from mutation spectra: a meta-analysis of histology-specific aberrations in cancer-derived cell lines.

Next-generation sequencing technologies have led to profound characterization of mutation spectra for several cancer types. Hence, we sought to systematically compare genomic aberrations between primary tumors and cancer lines. For this, we compiled publically available sequencing data of 1651 genes across 905 cell lines. We used them to characterize 23 distinct primary tumor sites by a novel approach that is based on Bayesian spam-filtering techniques. Thereby, we confirmed the strong overall similarity of alterations between patient samples and cell culture. However, we also identified several suspicious mutations, which had not been associated with their cancer types before. Based on these characterizations, we developed the inferring cancer origins from mutation spectra (ICOMS) tool. On our cell line collection, the algorithm reached a prediction specificity rate of 79%, which strongly variegated between primary cancer sites. On an independent validation cohort of 431 primary tumor samples, we observed a similar accuracy of 71%. Additionally, we found that ICOMS could be employed to deduce further attributes from mutation spectra, including sub-histology and compound sensitivity. Thus, thorough classification of site-specific mutation spectra for cell lines may decipher further genome-phenotype associations in cancer.

EANM Dosimetry Committee series on standard operational procedures for pre-therapeutic dosimetry II. Dosimetry prior to radioiodine therapy of benign thyroid diseases.

The EANM Dosimetry Committee Series "Standard Operational Procedures for Pre-Therapeutic Dosimetry" (SOP) provides advice to scientists and clinicians on how to perform patient-specific absorbed dose assessments. This particular SOP describes how to tailor the therapeutic activity to be administered for radioiodine therapy of benign thyroid diseases such as Graves' disease or hyperthyroidism. Pretherapeutic dosimetry is based on the assessment of the individual (131)I kinetics in the target tissue after the administration of a tracer activity. The present SOP makes proposals on the equipment to be used and guides the user through the measurements. Time schedules for the measurement of the fractional (131)I uptake in the diseased tissue are recommended and it is shown how to calculate from these datasets the therapeutic activity necessary to administer a predefined target dose in the subsequent therapy. Potential sources of error are pointed out and the inherent uncertainties of the procedures depending on the number of measurements are discussed. The theoretical background and the derivation of the listed equations from compartment models of the iodine kinetics are explained in a supplementary file published online only.

Development of hypothyroidism during long-term follow-up of patients with toxic nodular goitre after radioiodine therapy.

OBJECTIVE: To investigate the cure rate and incidence of hypothyroidism of radioiodine treatment with a calculated dose regimen and an intended thyroid dose of 150 Gy in patients with toxic nodular goitre during long-term follow-up. PATIENTS: A total of 265 consecutive patients with toxic nodular goitre were treated between March 2003 and August 2004 at our institute and followed up for a maximum of 8 years. Preliminary radioiodine testing with volumetric measurement of the thyroid by ultrasound as well as individual thyroidal radioiodine uptake and half-life measurements were performed before radioiodine therapy. The estimated radiation dose to the thyroid was 150 Gy. MEASUREMENTS: Follow-up controls with respect to success of therapy and development of hypothyroidism were performed 3 months, 1 and up to 8 years after radioiodine treatment. The relation of the achieved thyroid dose to the success rate of treatment and to the incidence of hypothyroidism was analysed. RESULTS: The cure rates were 85% at 3 months, 98% at 1 year and 98% at the end of follow-up. Above an achieved thyroid dose of more than 120 Gy, there was no significant association between the dose achieved in the thyroid and the cure rate on follow-up. The incidences of hypothyroidism at 3 months, at 1 year and at the end of follow-up were 32%, 55% and 73%, respectively. CONCLUSIONS: Radioiodine treatment with a calculated dose regimen is a highly effective treatment option in patients with toxic goitre with an overall success rate of 98%. However, radioiodine treatment with an intended thyroid dose of 150 Gy leads to a high incidence of hypothyroidism on long-term follow-up. This finding supports the suggestion that in future intended thyroid doses could be lowered in patients treated with a calculated dose regimen for toxic nodular goitre.

GATE based Monte Carlo simulation of planar scintigraphy to estimate the nodular dose in radioiodine therapy for autonomous thyroid adenoma.

The recommended target dose in radioiodine therapy of solitary hyperfunctioning thyroid nodules is 300-400Gy and therefore higher than in other radiotherapies. This is due to the fact that an unknown, yet significant portion of the activity is stored in extranodular areas but is neglected in the calculatory dosimetry. We investigate the feasibility of determining the ratio of nodular and extranodular activity concentrations (uptakes) from post-therapeutically acquired planar scintigrams with Monte Carlo simulations in GATE. The geometry of a gamma camera with a high energy collimator was emulated in GATE (Version 5). A geometrical thyroid-neck phantom (GP) and the ICRP reference voxel phantoms "Adult Female" (AF, 16ml thyroid) and "Adult Male" (AM, 19ml thyroid) were used as source regions. Nodules of 1ml and 3ml volume were placed in the phantoms. For each phantom and each nodule 200 scintigraphic acquisitions were simulated. Uptake ratios of nodule and rest of thyroid ranging from 1 to 20 could be created by summation. Quantitative image analysis was performed by investigating the number of simulated counts in regions of interest (ROIs). ROIs were created by perpendicular projection of the phantom onto the camera plane to avoid a user dependant bias. The ratio of count densities in ROIs over the nodule and over the contralateral lobe, which should be least affected by nodular activity, was taken to be the best available measure for the uptake ratios. However, the predefined uptake ratios are underestimated by these count density ratios: For an uptake ratio of 20 the count ratios range from 4.5 (AF, 1ml nodule) to 15.3 (AM, 3ml nodule). Furthermore, the contralateral ROI is more strongly affected by nodular activity than expected: For an uptake ratio of 20 between nodule and rest of thyroid up to 29% of total counts in the ROI over the contralateral lobe are caused by decays in the nodule (AF 3 ml). In the case of the 1ml nodules this effect is smaller: 9-11% (AF) respectively 7-8% (AM). For each phantom, the dependency of count density ratios upon uptake ratios can be modeled well by both linear and quadratic regression (quadratic: r(2)>0.99), yielding sets of parameters which in reverse allow the computation of uptake ratios (and thus dose) from count density ratios. A single regression model obtained by fitting the data of all simulations simultaneously did not provide satisfactory results except for GP, while underestimating the true uptake ratios in AF and overestimating them in AM. The scintigraphic count density ratios depend upon the uptake ratios between nodule and rest of thyroid, upon their volumes, and their respective position in a non-trivial way. Further investigations are required to derive a comprehensive rule to calculate the uptake or dose ratios based on post-therapeutic scintigraphy.

Follow-up on thyroidal uptake after radioiodine therapy: how robust is the peri-therapeutic dosimetry?

Radioiodine therapy (RIT) for benign thyroid diseases in Germany requires the patient to stay in a nuclear medicine therapy ward for at least 48 hours and the dose to the thyroid to be computed from activity measurements performed during that stay. A major part of the total dose will be delivered after the patient's discharge from the hospital and thus has to be predicted through extrapolation with the effective half-life measured peri-therapeutically. We performed repeated thyroid uptake measurements on patients up to five months post therapy to investigate post-therapeutic changes in their effective half-lives and examine the dosimetric consequences. 12 patients (4 m, 8 f; age 36 - 76 y; 4 Graves' disease, 4 toxic adenoma, 3 toxic goitre, 1 non-toxic goitre) underwent late uptake measurements (1 - 7 meas., 13 - 154 d post administration, median 54 d, performed with thyroid probe resp. whole body counter at lower activities). Doses calculated from late measurements were compared to those predicted at discharge; half-lives calculated from the late measurement closest to the median delay (54 d) were compared to those determined at time of discharge. A cross-calibration between activity calibrator, thyroid probe, and whole body counter over an activity range from 52 MBq down to 45 Bq revealed linearity to within 6%, which was considered sufficient. In 9 out of 12 patients the achieved dose was within the range predicted at discharge. Averaged deviation between achieved and predicted dose was 3.1±2.2% (median 2.5%, range 0.7% - 7.2%). Averaged deviation between post- and peri-therapeutic half-lives was 5.1±3.9% (median 3.5%, range 1.3% - 12.5%). For n=5 patients discharged after 3 days, averaged deviations were greater (dose 4.0%, half-life 5.6%) than for those patients (n=7) who stayed in the hospital for a minimum of 4 days (dose 2.5%, half-life 4.8%). Excretion of iodine from the thyroid remains practically unchanged for at least two months after RIT. The dosimetric procedure implemented in our institution warrants a robust prediction of the post-therapeutic half-life and thus the actual achieved dose.

Dosimetry for 131I-MIBG therapies in metastatic neuroblastoma, phaeochromocytoma and paraganglioma.

PURPOSE: Radiation dosimetry is a basic requirement for targeted radionuclide therapies (TRT) which have become of increasing interest in nuclear medicine. Despite the significant role of the radiopharmaceutical (131)I-metaiodobenzylguanidine (MIBG) for the treatment of metastatic neuroblastoma, phaeochromocytoma and paraganglioma details for a reliable dosimetry are still sparse. This work presents our procedures, the dosimetric data and experiences with TRT using (131)I-MIBG. METHODS: A total of 21 patients were treated with (131)I-MIBG between 2004 and 2008 according to a clearly defined protocol. Whole-body absorbed doses were determined by a series of scintillation probe readings for all 21 cases. Tumour absorbed doses were calculated on the basis of quantitative imaging for an entity of 25 lesions investigated individually using the region of interest (ROI) technique based on five scans each. RESULTS: Typical whole-body absorbed doses are found in the region of 2 Gy (range: 1.0-2.9 Gy) whereas tumour absorbed doses in turn cover a span between 10 and 60 Gy. Nonetheless this variation of tumour absorbed doses is comparatively low. CONCLUSION: The trial protocol in use is a substantial advancement in terms of reliable dosimetry. A clearly defined modus operandi for MIBG therapies should involve precisely described dosimetric procedures, e.g. a minimum of 20 whole-body measurements using a calibrated counter and at least four gamma camera scans over the whole period of the inpatient stay should be carried out. Calculation of tumour volumes is accomplished best via evaluation of SPECT and CT images.

Radioiodine therapy of benign thyroid disorders: what are the effective thyroidal half-life and uptake of 131I?

AIM: The use of radioiodine therapy is common in the treatment of benign thyroid disease. Council directive Euratom 97/43 requires that for all medical exposure of individuals for radiotherapeutic purposes exposures of target volumes should be individually planned. There are several strategies to accomplish this aim for radioiodine therapy including individual radioiodine uptake measurement and using either individual or mean effective radioiodine uptake and half-life. Although it is always simple to use standard activities, the effective thyroidal half-life and thyroidal uptake of I needs to be estimated individually to achieve optimal dosimetric results. We analyzed the radioiodine half-life and uptake in a large number of patients for use in a semi-individual calculation. METHODS: Patients presenting consecutively between 1 January 2006 and 31 December 2007 were included in the study. Inclusion criteria were the control of hyperthyroidism and withdrawal of antithyroid drugs 2 days before preliminary radioiodine testing and therapy. Patients were treated for Graves' disease (n=363), nontoxic goitre (n=50), toxic goitre (n=639), or toxic uninodular adenoma (n=365). The effective half-life and uptake of I were estimated by uptake measurements after 24 h and 5 days during the preliminary radioiodine test, and serial measurements over 5 days during therapy. RESULTS: The mean effective half-life of I measured during radioiodine therapy was 5.4 days in Graves' disease, 6.4 days in nontoxic goitre, 6.6 days in toxic goitre, and 5.7 days in toxic uninodular adenoma. The mean maximal uptake of I measured during radioiodine therapy was 64% in Graves' disease, 42% in nontoxic goitre, 38% in toxic goitre, and 31% in toxic uninodular adenoma. CONCLUSION: These actual values analyzed here might be used for a semi-individual calculation of therapeutic activity when an individual approach is not possible.

PROLARA: prognosis-based lifetime attributable risk approximation for cancer from diagnostic radiation exposure.

PURPOSE: To evaluate the impact of the reduced life expectancy of patients (compared to a nonpatient group with the same age distribution) on their nominal risk of developing cancer from the diagnostic use of radiation. METHOD: We define a "prognosis-based lifetime attributable risk modifier" (PROLARM) as the ratio of the risks for nonpatients and patients, a dimensionless quantity which indicates how strongly the life-time attributable risk (LAR) is reduced due to a patient's prognosis. An approximation to this ratio can be given (named PROLARA) which depends only on the patient's age at exposure and his/her life expectancy, but is independent of the exact choice of values for the baseline risk of cancer incidence and the excess relative risk (ERR) from radiation exposure. PROLARM and PROLARA were computed for a cohort of 4,285 female patients with metastatic breast cancer, for whom all necessary input data were available. RESULTS: LAR of solid cancer was significantly decreased in these patients: PROLARM >20 for age at exposure < or = 65 years. For any reasonable choice of function for ERR, the approximation PROLARA gave a lower estimate of the reduction in risk. The risk for a patient from the above cohort, exposed at age 50 years, is decreased by a factor of 29 (PROLARM) and 27 (PROLARA). In other words, 50 mSv in a patient with metastatic breast cancer corresponds risk-wise to only 2 mSv in a nonpatient of the same age. CONCLUSION: A major proportion of the total dose from diagnostic medical exposures does not constitute an additional cancer risk due to the poorer prognosis of patients compared to nonpatients of same gender and age. Our new PROLARA concept allows an estimation of the reduction in risk for any pathology when the associated survival is known.

Downregulation of 18F-FDG uptake in PET as an early pharmacodynamic effect in treatment of non-small cell lung cancer with the mTOR inhibitor everolimus.

UNLABELLED: Everolimus downregulates glucose metabolism-associated genes in preclinical models. Inhibition of glucose metabolism measured by (18)F-FDG PET was postulated to serve as a pharmacodynamic marker in everolimus-treated non-small cell lung cancer (NSCLC) patients. METHODS: In 8 NSCLC patients treated with everolimus, the percentage change in (18)F-FDG PET uptake (days 8 and 28 relative to baseline) was determined using a variety of summed standardized uptake value (SUV) measures. Both maximum and mean SUVs were used, with normalizations to body surface area and body weight and with and without correcting for plasma glucose levels. RESULTS: In 5 patients, a reduction of (18)F-FDG PET uptake on day 8 was observed with all methods, ranging from -12.8% to -72.2%. CONCLUSION: These observations demonstrate that inhibition of glucose metabolism is an early effect of everolimus treatment in NSCLC patients and can be assessed using (18)F-FDG PET.

[Should all patients with thyroid nodules > or = 1 cm undergo fine-needle aspiration biopsy?]. / Soll man alle Schilddrüsenknoten > or = 1 cm punktieren?

The prevalence of thyroid nodules > or = 1 cm is high in a previously iodine-deficient area. Under the hypothesis, that all patients with such nodules undergo fine-needle aspiration biopsy (FNAB) and that sensitivity and specificity of cytology are calculated with 85%, the positive predictive value of pathologic cytologic finding will reach 1.5% only according to Bayes-theorem. This is clinically unacceptable, as resection will be the consequence in all cases with suspect cytology. Even implementation of a second, independent test (e. g. moleculargenetic testing of thyreocytes, sensitivity to detect mutation 50%, specificity 95%) and application of sequential Bayes-theorem the positive predictive value of combined pathologic findings will increase to 13% only. Nevertheless, 58% out of all thyroid cancer remain undetected by such a sequential algorithm. As a consequence , pre-selection of thyroid nodules for FNAB is required to increase the pretest-probability to at least 5-10%. A combination of sonographic criteria and scintigraphy, even in patients with normal TSH-levels, is suited to selected thyroid nodules for FNAB.

Mean and maximum standardized uptake values in [18F]FDG-PET for assessment of histopathological response in oesophageal squamous cell carcinoma or adenocarcinoma after radiochemotherapy.

PURPOSE: To evaluate the potential of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the assessment of histopathological response and survival after neoadjuvant radiochemotherapy in patients with oesophageal cancer. PATIENTS AND METHODS: In 2005 and 2006, 55 patients (43 men, 12 women; median age 60 years) with locally advanced oesophageal cancer (cT3-4 Nx M0; 24 with squamous cell carcinoma, 31 with adenocarcinoma) underwent transthoracic en bloc oesophagectomy after completion of treatment with cisplatin, 5-fluorouracil, and radiotherapy ad 36 Gy in a prospective clinical trial. Of the 55 patients, 21 (38%) were classified as histopathological responders (<10% vital residual tumour cells) and 34 (62%) as nonresponders. FDG-PET was performed before (PET 1) and 3-4 weeks after the end (PET 2) of radiochemotherapy with assessment of maximum and average standardized uptake values (SUV) for correlation with histopathological response and survival. RESULTS: Histopathological responders had a slightly higher baseline SUV than nonresponders (p<0.0001 between PET 1 and PET 2 for responders and nonresponders) and the decrease was more prominent in responders. Except for SUVmax in patients with squamous cell carcinoma neither baseline nor preoperative SUV nor percent SUV reduction correlated significantly with histopathological response. Histopathological responders had a 2-year overall survival of 91 +/- 9% and nonresponders a survival of 53 +/- 10% (p = 0.007). CONCLUSION: Our study does not support recent reports that FDG-PET predicts histopathological response and survival in patients with locally advanced oesophageal cancer treated by neoadjuvant radiochemotherapy.

Smoking upregulates alpha4beta2* nicotinic acetylcholine receptors in the human brain.

The role of the alpha4beta2* nicotinic acetylcholine receptors (nAChR) in tobacco addiction in humans is largely unresolved. We visualized brain alpha4beta2* nicotinic acetylcholine receptors of smokers and non-smokers with positron emission tomography using 2-[(18)F]fluoro-3-(2(S)azetidinylmethoxy)pyridine, commonly known as 2-[(18)F]F-A-85380. The total brain distribution volume of 2-[(18)F]F-A-85380 was significantly increased in smokers. Statistical parametric mapping revealed that the most prominent regional differences of distribution volumes (DV) were found in cerebellum and brainstem with an increased uptake in smokers. The up-regulation of alpha4beta2* nAChR upon chronic nicotine exposure via tobacco smoking incorporates subcortical brain regions which may play an important role in nicotine addiction.

Incidence of postradioiodine immunogenic hyperthyroidism/Graves' disease in relation to a temporary increase in thyrotropin receptor antibodies after radioiodine therapy for autonomous thyroid disease.

BACKGROUND: The aim of the study was to analyze retrospectively the incidence of postradioiodine immunogenic hyperthyroidism/Graves' disease in relation to a temporary increase in TSH-receptor antibodies without overt hyperthyroidism after radioiodine therapy for autonomous thyroid disease. PATIENTS AND METHODS: Between May 2000 and May 2003 all patients (n = 1,357) who had undergone radioiodine therapy for autonomous thyroid disease were retrospectively analyzed for development of postradioiodine immunogenic hyperthyroidism. On pretreatment evaluation 565 of 1,357 patients (41.6%) had unifocal autonomous thyroid disease (UFA), 693 of 1,357 patients (51.1%) had multifocal autonomous thyroid disease (MFA), and 99 of 1,357 patients (7.3%) had diffuse thyroid disease (DISS). Free triiodothyronine (FT(3)), free thyroxine (FT(4)), thyrotropin (TSH), and thyroid antibodies were measured. Ultrasound examinations and thyroid scintigraphy were performed before and after radioiodine therapy. A sensitive assay with the human TSH receptor as antigen was chosen for measurement of the TSH receptor antibody and the study was limited to analysis of data obtained since introduction of this assay. RESULTS: Fifteen of 1,357 patients (1.1%) (UFA, 8/565 = 1.4%; MFA, 6/693 = 0.9%; DISS 1/99 = 1.0%) developed postradioiodine hyperthyroidism between 1 and 13 months after radioiodine therapy with clinically overt hyperthyroidism and an elevation of TSH receptor antibodies. Patients with elevated thyroid peroxidase (TPO) antibodies before radioiodine therapy had an almost 10-fold (6/57 patients =10.5%) higher risk of developing postradioiodine immunogenic hyperthyroidism. Thirteen of 999 patients (1.3%) with antibody measurements after radioiodine therapy (UFA, 2/421 = 0.5%; MFA, 9/494 = 1.8%, DISS, 2/84 = 2.4%) had increased levels of TSH receptor antibodies and, to some extent, TPO antibodies without development of clinically overt hyperthyroidism. CONCLUSIONS: There is an estimated 1.1% risk of developing postradioiodine immunogenic hyperthyroidism/Graves' disease in patients undergoing radioiodine therapy for autonomous thyroid disease and this increases approximately 10-fold when TPO antibody levels are elevated before radioiodine therapy. Furthermore, there is an estimated 1.3% risk of a temporary increase of TSH receptor antibodies after radioiodine therapy for autonomous thyroid disease without development of clinically overt hyperthyroidism.

Treatment of refractory Hodgkin's lymphoma patients with an iodine-131-labeled murine anti-CD30 monoclonal antibody.

PURPOSE: Hodgkin's lymphoma (HL) has been demonstrated to be a good target for immunotherapy since lymphocyte activation markers such as CD30 are expressed in high numbers on the malignant cells. Thus, we developed a new radioimmunoconjugate consisting of the murine anti-CD30 monoclonal antibody (MAb) Ki-4 labeled with iodine-131 ((131)I). PATIENTS AND METHODS: The biodistribution of (131)I-Ki-4 was assessed via dosimetry after preinfusion of 5 mg native Ki-4 followed by 250 to 300 MBq (131)I-labeled Ki-4. Whole-body scintigraphy was performed 1 hour, 24 hours, 48 hours, 72 hours, and 6 days after the infusion. Dosimetry was calculated using the programs NucliDose ICON-IDL (version 5.0.2; Siemens, Erlanger, Germany) and MIRDOSE (version 3.1; Oak Ridge National Laboratories; Oak Ridge, TN). The therapeutic dose was given on day 8 after preinfusion of unlabeled Ki-4. RESULTS: We treated 22 patients with relapsed or refractory CD30-positive HL. Preinfusion of 5 mg native Ki-4 was sufficient to bind the soluble CD30. Imaging demonstrated localization of involved areas measuring 5 cm in diameter or more in four patients and 2.5 cm in one patient. Patients received total body doses of 0.035 Gy to 0.99 Gy. Acute toxicity was mild with grade 1 fatigue in 19 of 22 assessable patients. Seven patients experienced grade 4 degrees hematotoxicity 4 to 8 weeks after treatment. Response included one complete remission, five partial remissions, and three minor responses. CONCLUSION: Treatment with (131)I-Ki-4 is effective but can be associated with severe hematotoxicity.

Imaging of central nervous system lymphomas with iodine-123 labeled rituximab.

Most patients with primary central nervous system (CNS) lymphoma (PCNSL) relapse after initial response to chemotherapy or the combination of chemotherapy and irradiation. Thus, novel treatment regimens for relapsed PCNSL are needed. As the majority of PCNSL are B-cell neoplasms expressing the CD20 antigen, treatment with the chimeric monoclonal antibody (MAb) rituximab might be reasonable. Nevertheless, the potential efficacy of intravenous rituximab in PCNSL seems to be limited as MAbs are high molecular weight proteins, which might be unable to pass the blood brain barrier. Thus, we performed dosimetric measurements with iodine-123 (123I)-rituximab to evaluate rituximab uptake in PCNSL after systemic intravenous administration. We analyzed four patients with PCNSL receiving a preinfusion of 250 mg/m2 rituximab followed by 200-500 MBq of the gamma-emitter 123I-rituximab. Single photon emission computed tomography (SPECT) was performed 1, 24 and 48 h after administration of the radio-immunoconstruct. Only one patient showed a very weak or questionable uptake of 123I-rituximab into tumor tissue which was ninefold lower compared with the blood-pool accumulation. These data suggest that systemic MAb-based radio-immunotherapy is not feasible in patients with PCNSL because a sufficient activity in the tumor will be associated with severe hematotoxicity. If an uptake of therapeutic rituximab doses into PCNSL can be achieved remains questionable.