FDG-PET/MRI in patients with pelvic recurrence of rectal cancer: first clinical experiences.

OBJECTIVES: To determine the value of 18F-FDG-PET/MRI in the diagnosis and management of patients with pelvic recurrence of rectal cancer. METHODS: Forty-four patients (16 women, 28 men) with a history of rectal cancer who received FDG-PET/MRI between June 2011 and February 2017 at our institution were retrospectively enrolled. Three patients received two FDG-PET/MRIs; thus a total of 47 examinations were included. Pelvic recurrence was confirmed either with histology (n = 27) or imaging follow-up (n = 17) (> 4 months). Two readers (one radiologist, one nuclear medicine physician) interpreted the images in consensus. Pelvic lesions were assessed regarding FDG uptake and morphology. Sensitivity, specificity, positive and negative predictive values as well as accuracy of PET/MRI in detecting recurrence were determined. RESULTS: In 47 FDG-PET/MRIs 30 suspicious pelvic lesions were identified, 29 of which were malignant. Two patients underwent resection and had histologically proven pelvic recurrence without showing suspicious findings on FDG-PET/MRI. Changes in management due to FDG-PET/MRI findings had been implemented in eight patients. Eighty per cent (16/20) of resected patients had histologically negative resection margins (R0), one patient had uncertain resection margins. Sensitivity of FDG-PET/MRI in detecting recurrence was 94%, specificity 94%, positive/negative predictive value and accuracy were 97%, 90% and 94%, respectively. CONCLUSIONS: FDG-PET/MRI is a valuable tool in the diagnosis and staging of pelvic recurrence in patients with rectal cancer. KEY POINTS: • Metabolic information obtained from PET coupled with excellent soft tissue contrast from MRI could facilitate detection of rectal cancer recurrence and assist in treatment planning. • PET/MRI demonstrates high sensitivity and specificity for the diagnosis of local recurrence of rectal cancer • PET/MRI led to alterations in management in 18.2% of patients.

Correction to: FDG-PET/MRI in patients with pelvic recurrence of rectal cancer: first clinical experiences.

The original version of this article, published on 6 July 2018, unfortunately contained a mistake.

Up-Regulation of PSMA Expression In Vitro as Potential Application in Prostate Cancer Therapy.

Possibilities to improve the therapeutic efficacy of Lu-177-PSMA-617 radionuclide therapy by modulation of target expression are being investigated. Knowledge on regulatory factors that promote prostate cancer (PCa) progression may contribute to targeting prostate cancer more effectively. We aimed at the stimulation of PCa cell lines using the substances 5-aza-2'-deoxycitidine (5-aza-dC) and valproic acid (VPA) to achieve increased prostate-specific membrane antigen (PSMA) expression. PC3, PC3-PSMA, and LNCaP cells were incubated with varying concentrations of 5-aza-dC and VPA to investigate the cell-bound activity of Lu-177-PSMA-617. Stimulation effects on both the genetically modified cell line PC3-PSMA and the endogenously PSMA-expressing LNCaP cells were demonstrated by increased cellular uptake of the radioligand. For PC3-PSMA cells, the fraction of cell-bound radioactivity was enhanced by about 20-fold compared to that of the unstimulated cells. Our study reveals an increased radioligand uptake mediated by stimulation for both PC3-PSMA and LNCaP cell lines. In perspective of an enhanced PSMA expression, the present study might contribute to advanced radionuclide therapy approaches that improve the therapeutic efficacy, as well as combined treatment options.

Combining Cisplatin with Different Radiation Qualities-Interpretation of Cytotoxic Effects In Vitro by Isobolographic Analysis.

BACKGROUND: The combination of platinum-containing cytostatic drugs with different radiation qualities has been studied for years. Despite their massive side effects, these drugs still belong to the therapeutic portfolio in cancer treatment. To overcome the disadvantages of cisplatin, our study investigated the cytotoxic effects of combining radionuclides with cisplatin. METHODS: FaDu cells were treated with cisplatin (concentration ≈ 2 µM) and additionally irradiated after two hours with the alpha-emitter 223Ra, the beta-emitter 188Re as well as external X-rays using dose ranges of 2-6 Gy. Cell survival was followed by colony formation assays and plotted against cisplatin concentration and radiation dose. The results were interpreted by isobolograms. RESULTS: Isobolographic analyses revealed a supra-additive cytotoxic effect for the combination of cisplatin and 223Ra. A sub-additive effect was observed for the combination of cisplatin and 188Re, whereas a protective effect was found for the combination with X-rays. CONCLUSIONS: The combination of cisplatin and 223Ra may have the potential to create a successfully working therapy scheme for various therapy approaches, whereas the combination with 188Re as well as single-dose X-ray treatment did not lead to a detectable radiosensitizing effect. Thus, the combination with alpha-emitters might be advantageous and, therefore, should be followed in future studies when combined with cytostatic drugs.

Epigenetic-Like Stimulation of Receptor Expression in SSTR2 Transfected HEK293 Cells as a New Therapeutic Strategy.

The aim of the study was to increase the uptake of the SSTR2-targeted radioligand Lu-177-DOTATATE using the DNA methyltransferase inhibitor (DNMTi) 5-aza-2'-deoxycytidine (5-aza-dC) and the histone deacetylase inhibitor (HDACi) valproic acid (VPA). The HEKsst2 and PC3 cells were incubated with variable concentrations of 5-aza-dC and VPA to investigate the uptake of Lu-177-DOTATATE. Cell survival, subsequent to external X-rays (0.6 or 1.2 Gy) and a 24 h incubation with 57.5 or 136 kBq/mL Lu-177-DOTATATE, was investigated via colony formation assay to examine the effect of the epidrugs. In the case of stimulated HEKsst2 cells, the uptake of Lu-177-DOTATATE increased by a factor of 28 in comparison to the unstimulated cells. Further, stimulated HEKsst2 cells demonstrated lower survival fractions (factor 4). The survival fractions of the PC3 cells remained almost unchanged. VPA and 5-aza-dC did not induce changes to the intrinsic radiosensitivity of the cells after X-ray irradiation. Clear stimulatory effects on HEKsst2 cells were demonstrated by increased cell uptake of the radioligand and enhanced SST2 receptor quantity. In conclusion, the investigated approach is suitable to stimulate the somatostatin receptor expression and thus the uptake of Lu-177-DOTATATE, enabling a more efficient treatment for patients with poor response to peptide radionuclide therapy (PRRT).

Early FDG PET at 10 or 20 Gy under chemoradiotherapy is prognostic for locoregional control and overall survival in patients with head and neck cancer.

PURPOSE: Our study aimed to explore the optimal timing as well as the most appropriate prognostic parameter of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) during chemoradiotherapy (CRT) for an early prediction of outcome for patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Serial PET data (before and three times during CRT) of 37 patients with advanced stage HNSCC, receiving combined CRT between 2005 and 2009, were evaluated. The maximum standardized uptake value (SUV(max)), the average SUV (SUV(mean)) and the gross tumour volume determined by FDG PET (GTV PET), based on a source to background algorithm, were analysed. Stratified actuarial analysis was performed for overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The median follow-up time was 26 months (range 8-50). RESULTS: For all patients, OS was 51%, DFS 44% and LRC 55% after 2 years. The 2-year OS (88%) and 2-year LRC (88%) were higher for patients whose SUV(max) of the primary tumour decreased 50% or more from the beginning (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT (ΔSUV(max10/20) ≥ 50%) than for patients with ΔSUV(max20) < 50% (2-year OS = 38%; p = 0.02; 2-year LRC 40%; p = 0.06). A pretreatment GTV PET below the median of 10.2 ml predicted a better 2-year OS (34% for GTV PET ≥ 10.2 ml vs 83% for GTV PET < 10.2 ml; p = 0.02). CONCLUSION: The decrease of SUV(max) from before (0 Gy) to week 1 or 2 (10 or 20 Gy) of CRT is a potential prognostic marker for patients with HNSCC. Because GTV PET depends on the applied method of analysis, we suggest the use of SUV(max), especially ΔSUV(max10/20), for an early estimation of therapy outcome. Confirmatory studies are warranted.

Third generation radioimmunoassay (RIA) for TSH receptor autoantibodies (TRAb) - one step less, similar results?

AIM: TSH-receptor (TSHR)-autoantibody (TRAb) is the serological hallmark of Graves' disease (GD). Recently, 3rd-generation radioimmunoassays (RIA) employing monoclonal TRAb such as M22 or T7 instead of TSH for the inhibition of human TRAb binding with solid-phase TSHR (coated tubes) have been introduced into laboratory routine. METHODS: As current assays typically employ a consecutive incubation of patient serum and labelled monoclonal TRAb, automation of TRAb RIA is a challenge. Thus, the assay procedure using human TSHR-coated tubes and the mouse monoclonal TRAb T7 was modified by combining both steps. The novel one-step method was compared with its corresponding consecutive 3rd-generation RIA by investigating 304 individuals encompassing 102 patients with active GD (GDa), 43 patients with GD after successful therapy (GDt), 31 with Hashimoto's disease (HD), 28 with non-autoimmune thyroid diseases (NAITD) and 100 healthy subjects (HS). RESULTS: With the new method, the incubation time was shortened by approximately one hour. Both 3rd-generation RIAs did not reveal a significantly different assay performance by comparing areas under the curve (AUC) with receiver operating characteristics curve analysis (AUC one-step: 0.94, AUC two-step: 0.96, p > 0.05, respectively). The two-step TRAb RIA demonstrated sensitivity and specificity values of 87.5 % and 96.2 %, respectively, whereas the one-step revealed 84.6 % and 96.2 %, respectively. CONCLUSION: One-step 3rd-generation RIA may be used for the reliable detection of TRAb. The shorter and easier assay design may improve its use and enable automation in routine nuclear medicine laboratories.

FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0.

The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about[18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out,interpret, and document quantitative FDG PET/CT examinations,but will concentrate on the optimisation of diagnostic quality and quantitative information.

On specificity of 2nd generation TSH receptor autoantibody measurements.

BACKGROUND: TSH receptor (TSHR) antibodies (TRAb) are the hallmark in the serological diagnosis of Graves' disease (autoimmune hyperthyroidism). Irrespective of receptor origin second generation TRAb assays have been shown to be more sensitive than original first generation assays. The specificity of both assay generations is claimed to be close to 100% for discriminating healthy individuals from Graves' disease patients. However, there are a small number of Hashimoto's thyroiditis (autoimmune hypothyroidism) patients demonstrating detectable TRAb. MATERIALS AND METHODS: One hundred and sixty-six Hashimoto's thyroiditis patients and 72 with Graves' disease were tested in second generation assays employing porcine and recombinant human TSHR. Receiver operating characteristics (ROC) were calculated for comparison. RESULTS: Using a threshold of 1.5 IU/L for both assays, 7 out of 166 Hashimoto's patients demonstrated positive TRAb in the human TSHR assay whereas only 1 patient was measured positive in the porcine TSHR assay (specificity: 95.8% and 99.4%, respectively). Seventy-one out of 72 Graves' disease patients were positive in the human TSHR assay whereas 70 showed positive results in the porcine TSHR assay (sensitivity: 98.6% and 97.2%, respectively; ROC p = 0.16). CONCLUSION: In this study, two commercial second generation TRAb assays with differing TSHR have been compared regarding the specificity in Hashimoto's thyroiditis patients. The slightly higher sensitivity of the human TSHR assay is obtained at the expense of a lower specificity. The impact of the different specificities should be considered due to the differing type of therapy for both patient groups.

Are porcine and human TSH receptor antibody measurements comparable?

BACKGROUND: The human TSH receptor antibody (TRAb) assay is reported to show higher sensitivity in comparison to the "classical" porcine TRAb testing. This claim is based on studies comparing porcine TSH receptor (TSH-R) in one type of assay system (non-immobilized TSH-R and PEG to separate bound and free) with recombinant human TSH-R in another type of assay system (TSH-R immobilized on plastic tubes). In this study isotopic TRAb assays both based on the "coated tube" system (second generation) were compared for the first time. MATERIALS AND METHODS: Three hundred and nineteen consecutive undiagnosed patients from Mainz University as well as 72 patients from Dresden University with known Graves' disease were tested in the human TRAb assay and in the porcine TRAb assay. Spearman's coefficient of rank correlation and Chi-square test statistical analysis was performed. RESULTS: In the 319 consecutive patients 35 patients (11.0%) were found positive in the human assay and 36 patients (11.3%) were positive in the porcine assay. Seventy patients with Graves' disease from Dresden were positive in the assay using the porcine TSH-R and 71 out of 72 patients showed positive results in the assay with the recombinant human TSH-R. The Spearman's coefficient of rank correlation for both patient cohorts was r = 0.932 and r = 0.891 (p < 0.001), respectively. There was no significant difference in the clinical assessment regarding the diagnosis of Graves' disease. CONCLUSION: There is no clinically relevant difference in isotopic TRAb second generation assays--independent of the TSH-R used. Both TSH-R assays showed nearly similar TRAb results in consecutive samples as well as in serum samples from patients with Graves' disease.

Radiosynoviorthesis (RSO): influencing factors and therapy monitoring.

OBJECTIVE: To evaluate the effectiveness of radiosynoviorthesis (RSO) in relation to joint type and underlying disease by both self-assessment of patients and scintigraphic assessment to determine conditions under which RSO might be preferable to the sole intra-articular corticoid injection. METHODS: Radiosynoviorthesis was performed on 136 patients for 424 joints [242 small, 130 medium-sized, and 52 large joints; 313 with rheumatoid arthritis (RA) and 111 with osteoarthritis (OA)]. The success of RSO was evaluated after 12 months by patients' estimation, and in 35 patients for 157 joints additionally by two-phase bone scintigraphy. The relative change in the scintigraphic uptake was compared with the patients' estimation. RESULTS: The subjectively estimated success rates for the small, medium-sized, and large joints were 89% (215/242), 86% (112/130), and 79% (41/52), and for RA and OA 89% (280/313) and 79% (88/111), respectively. The scintigraphically determined response rates for small and medium-sized joints were 81% (86/106) and 69% (35/51), respectively. There was a mismatch between patients' assessment and scintigraphic assessments in 18% (28/157) with 6 false-negative and 22 false-positive estimations using scintigraphy as the standard of reference. CONCLUSIONS: The success of RSO is higher in patients with RA than in patients with OA. For the finger, ankle, and wrist joints in RA, RSO is so promising that we would like to advocate its preference over the sole intraarticular corticoid injection. Perfusion bone scintigraphy can be used for therapy monitoring and earlier switching to RSO by showing that other therapies have failed.

A novel third-generation TSH receptor antibody (TRAb) enzyme-linked immunosorbent assay based on a murine monoclonal TSH receptor-binding antibody.

TSH receptor (TSHR) autoantibody (TRAb) is the serological hallmark of Graves' disease (GD). Third-generation enzyme-linked immunosorbent assays (ELISAs) using monoclonal TRAbs instead of TSH have been found useful for TRAb analysis recently. For the first time, a mouse monoclonal antibody (mAb) against TSHR was analyzed for TRAb detection and compared with human mAb M22 and TSH by the same competitive binding assay technique. A mouse monoclonal antibody (T7) binding to the TSH receptor and inhibiting TSH binding was generated and used for TRAb analysis in a third-generation ELISA. Obtained TRAb levels were compared with a second-generation TRAb assay employing bovine TSH and a third-generation assay with human mAb M22 as TSHR-binding reagents by investigating 89 patients with GD, 56 with Hashimoto's thyroiditis (HT), 73 with non-autoimmune thyroid diseases, 17 with rheumatoid arthritis, and 100 healthy subjects. The T7-based TRAb ELISA did not reveal a significantly different assay performance (area under the curve [AUC]) in contrast to the TSH and M22-based TRAb ELISAs by receiver operating characteristic (ROC) curve analysis (AUC-T7 0.967, AUC-TSH 0.972, AUC-M22 0.958, p > 0.05, respectively). After adjustment of cutoffs by ROC, all three TRAb ELISAs demonstrated sensitivities and specificities above 89.9% and 96.0%, respectively. Both third-generation TRAb ELISAs showed a tendency for a higher prevalence of TRAb positives in HT in contrast to the second-generation ELISA. Mouse mAbs against the TSHR may be used for the reliable detection of TRAb by third-generation TRAb ELISA. The earlier reported higher sensitivity of third-generation TRAb ELISA in GD needs to be considered in the context of a slightly lower specificity regarding HT.

Feasibility of high activity rhenium-188-microsphere in hepatic radioembolization.

BACKGROUND: This paper describes the feasibility of intra-arterial high-activity administration of (188)Re-microspheres. METHODS: Patients with unresectable colorectal liver metastases or hepatocellular cancer (HCC) received single treatments with (188)Re-microspheres. The administered activity was calculated to give a liver dose of 100 Gy. From post-therapeutic scans and urine sampling, the dose to the liver, metastases and bladder was calculated. Toxicity was assessed up to 3 months after administration by means of the Common Terminology Criteria for Adverse Events v3.0 (Trotti et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003;13(3):176-81). Response was evaluated on CT. RESULTS: 13.6 +/- 4.7 GBq (188)Re-microspheres was administered selective in the feeding artery of the tumour to 10 patients (3 x HCC and 7 x colorectal liver metastases). There was a low urinary excretion rate of 8.9 +/- 3.8% of administered activity within 96 h. The absorbed dose to the tumour, normal liver (excluding the tumour) and bladder was 10.24 +/- 5.02 Gy/GBq (128 +/- 47 Gy), 3.94 +/- 2.52 Gy/GBq (50 +/- 33 Gy) and 0.27 +/- 0.20 Gy/GBq (2.4 +/- 1.9 Gy), respectively. There was an acceptable rate of toxicity in 30% of grades I and II, respectively, and 10% with grade III. There was reversible in the most patients within 14 days after treatment. The response was assessed on CT: two patients had a partial response (PR), five patients had stable disease and three patients had disease progression. CONCLUSION: Treatment of colorectal liver metastases or HCC using high activities of (188)Re-microspheres was well tolerated and a PR was seen in 2 of 10 patients. The treatment represents a therapeutic option in these patients.

A comparative study of 188Re-HEDP, 186Re-HEDP, 153Sm-EDTMP and 89Sr in the treatment of painful skeletal metastases.

AIM: The surface bone-seeking radiopharmaceuticals 188Re-HEDP, 186Re-HEDP and 153Sm-EDTMP, and the volume seeker 89Sr were investigated to determine the efficacy and toxicity in pain palliation of bone metastases. METHOD: The effect of treatment with 188Re-HEDP, 186Re-HEDP, 153Sm-EDTMP and 89Sr on pain symptoms, quality of life, and bone marrow function were studied. In total, 79 patients (18 with breast cancer and 61 with prostate cancer) were treated (31 patients with 188Re-HEDP, 15 patients each with 186Re-HEDP and 153Sm-EDTMP, and 18 patients with 89Sr). All patients were interviewed using standardized sets of questions before and after therapy weekly for 12 weeks. Blood counts were taken weekly for 6 weeks and after 12 weeks. RESULTS: In total, 73% of patients reported pain relief (77% after 188Re-HEDP, 67% after 186Re-HEDP 73% after 153Sm-EDTMP, and 72% after 89Sr). Fifteen percent of patients could discontinue their analgesics and were pain-free. Pain showed a decrease from 3.6+/-1.7 to a maximum of 2.2+/-1.8 at visual analogue scale in 10 steps (P<0.01). Patients described an improvement on the Karnofsky performance scale from 70+/-10% to 78+/-14% 12 weeks after treatment (P=0.15). There were eight patients with a thrombocytopenia grade I, two patients with grade II and one with grade III. The maximum nadir of platelet and leukocyte counts were observed between the 2nd to 5th week after treatment and was reversible within 12 weeks. There were no significant differences in pain palliation, Karnofsky performance status (KPS) and bone marrow toxicity between the different radionuclides (P=0.087-0.449). CONCLUSION: All radiopharmaceuticals were effective in pain palliation, without induction of severe side effects or significant differences in therapeutic efficacy or toxicity.

The floating Meckel.

A 10-year-old girl was hospitalized because of abdominal pain and significant gastrointestinal bleeding for 3 days with hematocrit of 28% and hemoglobin of 6.1 mmol/L. Gastroscopy and abdominal ultrasound did not reveal any gastrointestinal abnormalities and parameters of coagulation were normal. Because a Meckel diverticulum is one of the most common causes of lower gastrointestinal bleeding in children, a Tc-99m pertechnetate scan (Meckel's scan) was performed to identify ectopic gastric mucosa. Normally, a Meckel diverticulum is found in the right lower quadrant.

Direct and Auger Electron-Induced, Single- and Double-Strand Breaks on Plasmid DNA Caused by 99mTc-Labeled Pyrene Derivatives and the Effect of Bonding Distance.

It is evident that 99mTc causes radical-mediated DNA damage due to Auger electrons, which were emitted simultaneously with the known γ-emission of 99mTc. We have synthesized a series of new 99mTc-labeled pyrene derivatives with varied distances between the pyrene moiety and the radionuclide. The pyrene motif is a common DNA intercalator and allowed us to test the influence of the radionuclide distance on damages of the DNA helix. In general, pUC 19 plasmid DNA enables the investigation of the unprotected interactions between the radiotracers and DNA that results in single-strand breaks (SSB) or double-strand breaks (DSB). The resulting DNA fragments were separated by gel electrophoresis and quantified by fluorescent staining. Direct DNA damage and radical-induced indirect DNA damage by radiolysis products of water were evaluated in the presence or absence of the radical scavenger DMSO. We demonstrated that Auger electrons directly induced both SSB and DSB in high efficiency when 99mTc was tightly bound to the plasmid DNA and this damage could not be completely prevented by DMSO, a free radical scavenger. For the first time, we were able to minimize this effect by increasing the carbon chain lengths between the pyrene moiety and the 99mTc nuclide. However, a critical distance between the 99mTc atom and the DNA helix could not be determined due to the significantly lowered DSB generation resulting from the interaction which is dependent on the type of the 99mTc binding motif. The effect of variable DNA damage caused by the different chain length between the pyrene residue and the Tc-core as well as the possible conformations of the applied Tc-complexes was supplemented with molecular dynamics (MD) calculations. The effectiveness of the DNA-binding 99mTc-labeled pyrene derivatives was demonstrated by comparison to non-DNA-binding 99mTcO4-, since nearly all DNA damage caused by 99mTcO4- was prevented by incubating with DMSO.

Radiation protection in radiosynovectomy of the knee.

Radiosynovectomy is a widely available therapeutic option that involves radiopharmaceutical injections into joints to treat rheumatoid arthritis. However, data on the beta-radiation dose equivalents for the staff performing such treatments are limited. The aim of this study was to determine the personal dose equivalents H(P)(0.07) to the skin of the hands of the treating physician under several exposure scenarios. An activity of 185 MBq (90)Y was used. Thermoluminescence detectors were attached at the finger tip of the thumb, forefinger, and middle finger of the treating physician. Measurements of beta-exposures were made during treatment of 70 knees with (90)Y under the following exposure scenarios: group 1, the radiosynovectomy was performed with syringe shield with Perspex (Plexiglas, Röhm GmbH, Germany) (thickness of 5 mm); group 2, additionally a manipulator was used for fixation of the needle; group 3, radiation-resistant gloves were added to the measures in groups 1 and 2. For group 1, the highest beta doses were measured at the forefinger (22.1 microSv MBq(-1)) (22,100 microrem/27 microCi) and thumb with 16.5 microSv MBq(-1) (16,000 microrem/27 microCi) at the left hand, which holds the needle (right-handed physician). In group 2, the radiation doses were reduced to 0.6 microSv MBq(-1) (60 microrem/27 microCi) at the left forefinger and 0.5 microSv MBq(-1) (50 microrem/27 microCi) at the left thumb. The use of a manipulator and special radiation resistant gloves reduced the radiation dose to 0.4 microSv MBq(-1) (40 microrem/27 microCi) at the left forefinger and to 0.3 microSv MBq(-1) (30 microrem/27 microCi) at the left thumb in group 3. It was concluded that while performing radiosynovectomy without a manipulator for fixation of the needle, the dose measured at the left forefinger could exceed the German limit of 500 mSv (50 rem) per year for the official dosimetry at the skin. Using holding forceps allows compliance with the legal limit and could considerably reduce the beta dose. The use of radiation-resistant gloves reduced the beta dose at the skin only slightly.

3-O-methyl-6-18F-fluoro-L-dopa, a new tumor imaging agent: investigation of transport mechanism in vitro.

UNLABELLED: (18)F-Labeled amino acids represent a promising class of imaging agents in tumors, particularly brain tumors. However, the determination of their potential to image peripheral tumors, possibly depending on individual transport characteristics, still remains an area of investigation. The present study investigated the transport mechanism for 3-O-methyl-6-(18)F-fluoro-L-dopa (OMFD), a novel (18)F-labeled phenylalanine derivative, into tumor cells. METHODS: OMFD has routinely and reliably been prepared for clinical use in 20%-25% radiochemical yield (decay corrected, related to (18)F-F(2)) using 6-(18)F-fluoro-L-3,4-dihydroxyphenylalanine preparation devices with minor modifications. In vitro uptake assays with HT-29 (human colon adenocarcinoma) cells, FaDu (squamous cell carcinoma) cells, and RBE4 (immortalized rat brain endothelial) cells were performed with OMFD under physiologic amino acid concentrations without and with the competitive transport inhibitors 2-aminobicyclo-[2,2,1]-heptane-2-carboxylic acid and alpha-(methylamino)isobutyric acid plus serine and without or with Na(+). RESULTS: Transport inhibition experiments using specific competitive inhibitors demonstrated that uptake of OMFD in all cell lines tested was mediated mainly by the sodium-independent high-capacity amino acid transport systems. The highest OMFD uptake was in FaDu cells. CONCLUSION: OMFD seems to be a promising PET tracer for imaging of amino acid transport in tumors.

99mTc-labeled HYNIC-DAPI causes plasmid DNA damage with high efficiency.

(99m)Tc is the standard radionuclide used for nuclear medicine imaging. In addition to gamma irradiation, (99m)Tc emits low-energy Auger and conversion electrons that deposit their energy within nanometers of the decay site. To study the potential for DNA damage, direct DNA binding is required. Plasmid DNA enables the investigation of the unprotected interactions between molecules and DNA that result in single-strand breaks (SSBs) or double-strand breaks (DSBs); the resulting DNA fragments can be separated by gel electrophoresis and quantified by fluorescent staining. This study aimed to compare the plasmid DNA damage potential of a (99m)Tc-labeled HYNIC-DAPI compound with that of (99m)Tc pertechnetate ((99m)TcO4(-)). pUC19 plasmid DNA was irradiated for 2 or 24 hours. Direct and radical-induced DNA damage were evaluated in the presence or absence of the radical scavenger DMSO. For both compounds, an increase in applied activity enhanced plasmid DNA damage, which was evidenced by an increase in the open circular and linear DNA fractions and a reduction in the supercoiled DNA fraction. The number of SSBs elicited by 99mTc-HYNIC-DAPI (1.03) was twice that caused by (99m)TcO4(-) (0.51), and the number of DSBs increased fivefold in the (99m)Tc-HYNIC-DAPI-treated sample compared with the (99m)TcO4(-) treated sample (0.02 to 0.10). In the presence of DMSO, the numbers of SSBs and DSBs decreased to 0.03 and 0.00, respectively, in the (99m)TcO4(-) treated samples, whereas the numbers of SSBs and DSBs were slightly reduced to 0.95 and 0.06, respectively, in the (99m)Tc-HYNIC-DAPI-treated samples. These results indicated that (99m)Tc-HYNIC-DAPI induced SSBs and DSBs via a direct interaction of the (99m)Tc-labeled compound with DNA. In contrast to these results, (99m)TcO4(-) induced SSBs via radical formation, and DSBs were formed by two nearby SSBs. The biological effectiveness of (99m)Tc-HYNIC-DAPI increased by approximately 4-fold in terms of inducing SSBs and by approximately 10-fold in terms of inducing DSBs.