Studying the General Toxicity and Cumulative Properties of a Radiopharmaceutical Nanocolloid, (99m)Tc-Al2O3.

We studied toxicity of a new Russian radiopharmaceutical Nanocolloid, (99m)Tc-Al2O3. Tests for acute toxicity showed that this agent belongs to a class of moderate-toxicity substances and does not have cumulative properties. The evaluation of subchronic toxicity after subcutaneous injection of this product to rats (0.04, 0.2, and 0.4 ml/kg) and rabbits (0.02 and 0.2 ml/kg) for 7 days did not reveal changes in the general state, temperature, body weight, indices of the peripheral blood and bone marrow, functions of the heart, liver, kidneys, and nervous system, and morphological characteristics of the internal organs in animals. The drug does not produce a local irritant effect.

[STUDYING ACUTE TOXICITY OF NEW RADIOPHARMACEUTICAL 99MTC-AL2O3 NANOCOLLOIDS FOR ONCOLOGICAL DIAGNOSTICS].

The acute toxicity of a new drug based on nanocolloidal gamma alumina labeled with technetium-99m (99mTc) has been studied on 80 rats (40 females and 40 males) and 80 mice (40 females and 40 males) with intraperitoneal and subcutaneous drug administration. A single administration of the pharmacological agent was followed by observation of the survival of animals for 14 days with determining tolerable, toxic, and lethal doses for intraperitoneal and subcutaneous administration according to the Litchfield - Wilcoxon method, establishing the causes of animal death within 14 days of observation, and studying the drug influence on the general condition and some functional and morphological indices. Based on the established boundaries of toxicity and the classification of toxicity, the 99mTc-Al2O3 nanocolloids can be classified into conditionally moderately toxic substances. The actual values of LD5 of the radiopharmaceutical fall in the range of large doses. The safety factor for the drug studied significantly exceeds the minimum permissible value of 100.

Molecular imaging and pharmacokinetics of (99m) Tc-hTERT antisense oligonucleotide as a potential tumor imaging probe.

Targeting and visualization of human telomerase reverse transcriptase (hTERT) represents a promising approach for providing diagnostic value. The uptake kinetics and imaging results of (99m) Tc-hTERT antisense oligonucleotides (ASON) in hTERT-expressing cells were examined in vitro and in vivo. The pharmacokinetics and acute toxicity studies of (99m) Tc-hTERT ASON were also performed. The labeling efficiencies of radiolabeled oligonucleotide reached 76 ± 5%, the specific activity was up to 1850 kBq/µg, and the radiochemical purity was above 96%. Radioactivity accumulated to a higher concentration in hTERT-expressing cells with antisense probe than with sense control (p < 0.05). Lipid carrier incorporation significantly increased the transmembrane delivery of radiolabeled probes (p < 0.05). hTERT-expressing xenografts in nude mice were clearly visualized at 6 h postinjection of the antisense probe but not the sense control probe. However, liposome did not increase the radioactivity accumulation of probes in tumors for either antisense or sense probe (p > 0.05). Radioactivity counts per minute versus time profiles for (99m) Tc-hTERT ASON were biphasic, indicative of a three-compartment model. The pharmacokinetics parameters of half-life of distribution (T1/2α ), half-life of elimination (T1/2ß ), total apparent volume of distribution (Vd), and total rate of clearance were 2.04 ± 0.48 min, 24 ± 4.8 min, 109.83 ± 17.20 mL, and 3.19 ± 0.17 mL/min, respectively. The acute toxicity study results showed the safe application of (99m) Tc-hTERT ASON in vivo. This study provides further evidences that (99m) Tc-hTERT ASON should be developed as a safe, potential molecular image-guided diagnostic agent.

Bioavailability, antioxidant and non toxic properties of a radioprotective formulation prepared from isolated compounds of Podophyllum hexandrum: a study in mouse model.

The current study was aimed to determine the stability, serum protein binding ability, biodistribution, antioxidant potential and tissue toxicity status of a novel radioprotective formulation (G-002M) from Podophyllum hexandrum. G-002M is the combination of a flavonoid, a lignan and its glucoside isolated from P. hexandrum rhizome that exhibit high radioprotective potential. Stability of G-002M tagged with 99mTc was observed in vitro and with mice serum till 24 hr of incubation. The formulation was investigated for its antioxidant status and its bioavailability and toxicity in different organs of mice. Biodistribution study of 99mTc-G-002M revealed its uptake by all the vital organs of mice. Higher absorbed dose was observed in lungs, liver, jejunum and kidney. Maximum retention of G-002M in kidney revealed that G-002M was excreted predominantly through renal route. G-002M was also observed to have high free radical scavenging and total reducing properties. Histopathological observations showed no significant alterations in tissue morphology of lungs, liver, jejunum and kidney by G-002M administration. The data conclusively demonstrate that high stability, multi organ availability, longer retention and non-toxic behavior of G-002M might help in exhibiting strong protective potential against lethal radiation.

Indocyanine green versus technetium-99m with blue dye for sentinel lymph node detection in early-stage cervical cancer: A systematic review and meta-analysis.

BACKGROUND: The fluorescent dye indocyanine green (ICG) has emerged as a promising tracer for intraoperative detection of sentinel lymph nodes (SLNs) in early-stage cervical cancer. Although researchers suggest the SLN detection of ICG is equal to the more conventional combined approach of a radiotracer and blue dye, no consensus has been reached. AIMS: We aimed to assess the differences in overall and bilateral SLN detection rates with ICG versus the combined approach, the radiotracer technetium-99m (99m Tc) with blue dye. METHODS AND RESULTS: We searched MEDLINE, Embase, and the Cochrane Library from inception to January 1, 2020 and included studies reporting on a comparison of SLN detection with ICG versus 99m Tc with blue dye in early-stage cervical cancer. The overall and bilateral detection rates were pooled with random-effects meta-analyses. From 118 studies retrieved seven studies (one cross-sectional; six retrospective cohorts) were included, encompassing 589 patients. No significant differences were found in the pooled overall SLN detection rate of ICG versus 99m Tc with blue dye. Meta-analyses of all studies showed ICG to result in a higher bilateral SLN detection rate than 99m Tc with blue dye; 90.3% (95%CI, 79.8-100.0%) with ICG versus 73.5% (95%CI, 66.4-80.6%) with 99mTc with blue dye. This resulted in a significant and clinically relevant risk difference of 16.6% (95%CI, 5.3-28.0%). With sensitivity analysis, the risk difference of the bilateral detection rate maintained in favor of ICG but was no longer significant (13.2%, 95%CI -0.8-27.3%). CONCLUSION: ICG appears to provide higher bilateral SLN detection rates compared to 99m Tc with blue dye in patients with early-stage cervical cancer. However, in adherence with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines, the quality of evidence is too low to provide strong recommendations and directly omit the combined approach of 99m Tc with blue dye.

Reverse Lymph Node Mapping Using Indocyanine Green Lymphography: A Step Forward in Minimizing Donor-Site Morbidity in Vascularized Lymph Node Transfer.

BACKGROUND: Reverse lymphatic mapping before harvesting a lymph node flap is crucial to avoid donor-site lymphedema; however, the technique is complex and unavailable in many centers. The authors introduce radioisotope-free reverse lymphatic mapping using indocyanine green and Patent Blue dye. METHODS: The authors conducted a prospective study in patients undergoing free vascularized groin lymph node transfer for postmastectomy upper extremity lymphedema. The day before surgery, 0.2 ml of technetium-99 was injected into the first and second web spaces of the ipsilateral foot. The following day, once the patient was anesthetized, indocyanine green was injected into the same web spaces of the same foot and Patent Blue dye was injected just proximal to the upper margin of the skin paddle of the lymph node flap. The main lymph nodes draining the limb were localized using indocyanine green lymphography and gamma probe. RESULTS: Thirty-nine patients underwent vascularized groin lymph node transfer with or without deep inferior epigastric artery perforator flap breast reconstruction. Navigation of the main lower extremity draining inguinal lymph nodes using the gamma probe and indocyanine green lymphography was identical in all patients. The blue-stained lymphatics in the skin paddle drained to the superficial proximal inguinal lymph node and were targeted for transfer. No donor-site lymphedema was reported, and lymphatic drainage of the lower extremity was preserved in all cases. CONCLUSIONS: Reverse lymphatic mapping using indocyanine green lymphography provides identical results to those using technetium-99 isotope scanning. However, indocyanine green is preferable in terms of safety and reproducibility and also avoids the complexity and hazards of radioisotope mapping. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Radiation exposure to surgical staff during hyperthermic isolated limb perfusion with 99m Technetium labeled red blood cells.

PURPOSE: Hyperthermic isolated limb perfusion (HILP) is an effective method in the treatment of recurrent melanomas and soft tissue sarcomas. To avoid systemic toxicity, leakage from the limb perfusate into the systemic circulation is real-time monitored by administration of a radioactive agent to the limb circuit. This has made HILP safe for the patient. However, the radiation exposure to the surgical staff has never been measured and could be a limiting factor for the use of HILP. The purpose of the present study was to measure and evaluate the radiation exposure to the surgical staff performing HILP with (99m)Technetium labeled red blood cells. MATERIALS AND METHODS: Thirteen patients had HILP performed in 11 lower limbs and two upper limbs at our inpatient clinic between October 2006 and February 2007. The surgeon and nurse had thermoluminescence dosimetry (TLD) chips attached to the finger pulp and to the ring area of the left fourth finger, as well as an electronic dosimeter attached to the anterior lining of the trousers. The anesthesiologist and perfusion technologist also carried electronic dosimeters. RESULTS: The surgeon had the highest radioactive exposure with an average dose per procedure to the finger pulp of 16.2 microSv, to the ring area of 8.5 microSv, and to the abdominal wall of 4.2 +/- 0.6 microSv. CONCLUSIONS: HILP with (99m)technetium-labeled red blood cells does not constitute a safety risk to the operating team with respect to radioactive exposure. Routine dose monitoring of the staff or special precautions for fertile women are not necessary.

Undesirable events with radiopharmaceuticals.

Radiopharmaceuticals are used in nuclear medicine for diagnostic and therapeutic purposes. Many adverse reactions and false positive reactions related to radiopharmaceuticals take place every day in hospitals, but most of them are not reported. It is therefore important to understand the definition of each undesirable reaction. Adverse reactions are defined as any noxious or unintended reactions to a drug, which is administered in standard doses through the proper route for the purpose of prophylaxis, diagnosis, or treatment. False positive reactions can be defined as any imaging appearance caused by undue physiological or pathological accumulation of radiopharmaceuticals. Information concerning these undesirable reactions is limited for radiopharmaceuticals. The present study intends to be a source of information that could be accessed by all nuclear medicine staff. A review of the literature from 1957 to January 2009 was carried out using the criteria of a systematic review, established by the Cochrane Collaboration, an international non-profit organization, that provides up-to-date information about the health care. The present study has revealed that radiopharmaceuticals cause adverse reactions. Six cases of adverse reactions with radiopharmaceuticals were found: 2 cases with (18)F-fluorodeoxyglucose (FDG) and 4 cases with technetium 99m ((99m)Tc). Among the 4 cases of adverse reactions with (99m)Tc, one subject who received (99m)Tc-labeled sestamibi developed anaphylactic reactions. Moreover, a total of 8 cases with false positive reactions were found with FDG. In conclusion, a worldwide effort should be made to report as many cases as possible of adverse events and false positive reactions with radiopharmaceuticals.

Characterization of resolution, sensitivity, and shielding of a gamma-probe for sentinel lymph node localization: an experimental study.

OBJECTIVE: The aim of this study was to evaluate angular, spatial, and energy resolution, sensitivity, and shielding of a gamma-probe. MATERIALS AND METHODS: The EUROPROBE II gamma-probe (EuroRad) with sources of technetium-99m was assessed according to NEMA NU-3-2004. Resolution tests were evaluated considering the full width at half maximum (FWHM). The following parameters were evaluated: angular resolution in air, spatial resolution with a scattering medium and in air, energy resolution, and sensitivity and shielding. The collimator was used to evaluate angular and spatial resolution, sensitivity, and shielding. Background radiation was considered and did not affect the counts. RESULTS: FWHM of angular resolution (at 3/30 cm) was 39.17°/33.13° with the collimator and 74.08°/71.51° without the collimator; FWHM of spatial resolution in air at 10 mm was 13.32 mm with the collimator and 21.23 mm without the collimator. Energy resolution (%FWHM) was 20.51%. Sensitivity at 10 mm was 4.642±5 cps/MBq without the collimator and 1.063±2 cps/MBq with the collimator; shielding effectiveness of the probe tip was 99.52%. Background was not relevant to the counts. CONCLUSION: We showed that the collimator improved angular and spatial resolution to the detriment of sensitivity. Feasible results of energy resolution, sensitivity, and shielding were achieved.

Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer with technetium 99m-labeled totally human monoclonal antibody 88BV59: results of pivotal, phase III multicenter studies.

PURPOSE: To assess the performance and potential clinical impact of a totally human monoclonal antibody, 88BV59 (HumaSPECT) (INTRACEL, Corp, Rockville, MD), in 202 assessable presurgical patients with recurrent, metastatic, or occult colorectal cancer. METHODS: 88BV59, labeled with technetium Tc 99m (99mTc) (HumaSPECT-Tc), was injected intravenously, and planar and single photon emission tomography (SPECT) images were obtained 14 to 20 hours postinjection. Surgical and pathologic verification of tumor were used as the standard against which the performance of HumaSPECT-Tc imaging and computed tomography (CT) analysis were evaluated. RESULTS: All patients entered onto the recurrent disease study had at least one tumor site defined on CT. The sensitivity of HumaSPECT-Tc in those CT-positive patients was 87%. The specificity of HumaSPECT-Tc was 57% compared with 17% for CT and the difference was statistically significant (P < .001). The diagnostic information provided by HumaSPECT-Tc significantly (P < .001) improved the accuracy of the identification of resectable and nonresectable disease over that of CT (80% v 62%). HumaSPECT-Tc scans resulted in a significant (P < .001) reduction versus CT in terms of the proportion of patients understaged (27% v 41%) and overstaged (4% v 26%). In patients with occult disease (increasing carcinoembryonic antigen [CEA] titer, negative diagnostic work-up, negative CT), HumaSPECT-Tc correctly identified disease in 15 of 22 (68%) patients. HumaSPECT-Tc images provided additional clinical data that would have affected patient management decisions in 40 of 202 (19.8%) patients. In 365 patients who received 88BV59, only a single detectable human anti-human antibody (HAHA) response (90 ng/mL) at 9 weeks postinfusion was observed. CONCLUSION: HumaSPECT-Tc can provide important and accurate information about the presence and location of disease in patients with a high clinical suspicion of metastatic or recurrent colorectal cancer and either positive (known disease) or negative (occult disease) CT scans.

Myelotoxicity and RBE of 211At-conjugated monoclonal antibodies compared with 99mTc-conjugated monoclonal antibodies and 60Co irradiation in nude mice.

UNLABELLED: The rationale of this study was to determine the myelotoxicity in nude mice of the alpha-emitter 211At conjugated to monoclonal antibodies (mAbs) and to compare the effect with an electron emitter, (99m)Tc, and external irradiation from a 60Co source, for estimation of the relative biological effectiveness (RBE). METHODS: 211At and (99m)Tc were conjugated to the IgG1 mAbs MX35 and 88BV59. Nude female BALB/c mice, 8- to 12-wk old, were injected intraperitoneally or intravenously. The biodistribution was determined 3, 6, and 18 h after injection. The bone-to-blood and bone marrow-to-blood activity concentration ratios (BBLR and BMBLR, respectively) were determined for simultaneously injected 211At- and (99m)Tc-mAbs. Bone marrow samples were taken from the femur. For each mouse, the whole-body retention was measured as well as the blood activity by repeated blood samples from the tail vein (0), 1, 3, 6, 12, and 18 h after injection. External-beam irradiation from a 60Co source was also performed at 3 different dose levels. White blood cell (WBC) counts, red blood cell counts, platelet counts, and hemoglobin were determined for each mouse initially and on days 1, 4, 5, 7, 15, 22, and 27 after injection. The calculations of the absorbed dose to the bone marrow were based on the BBLR, BMBLR, the cumulated activities, and the absorbed fractions. The absorbed fractions, phi, for alpha-particles and electrons in the bone marrow were calculated using Monte Carlo simulations based on a bone marrow dosimetry model. RESULTS: The BMBLR was 0.58 +/- 0.06 and 0.56 +/- 0.06 for the 211At- and (99m)Tc-mAbs, respectively. No significant variation in BMBLR with time was found. The absorbed fractions for alpha-particles and electrons in the bone marrow were 0.88 and 0.75, respectively. The mean absorbed fractions of the photons from (99m)Tc were 0.033 and 0.52 for 140 and 18.3 keV, respectively. When different amounts of 211At- and (99m)Tc-mAbs (0.09-1.3 and 250-1,300 MBq, respectively) were administered intraperitoneally or intravenously, corresponding to absorbed doses to the bone marrow of 0.01-0.60 and 0.39-1.92 Gy, respectively, the WBC counts was suppressed by 1%-90% and 23%-89%, respectively. When external-beam irradiation with a 60Co source was performed to absorbed doses of 1.4, 1.9, and 2.4 Gy, the WBC counts was suppressed by 47%-90%. These results indicate a myelotoxic in vivo RBE of 3.4 +/- 0.6 for alpha-particles compared with (99m)Tc and 5.0 +/- 0.9 compared with 60Co irradiation. CONCLUSION: The effect on the WBC counts from bone marrow irradiation with 211At-mAbs indicates an in vivo RBE of 3.4 +/- 0.6 in comparison with (99m)Tc-mAbs. The RBE value compared with external irradiation is 5.0 +/- 0.9.

Safety and biodistribution of 99mTechnetium-labeled anti-CD44v6 monoclonal antibody BIWA 1 in head and neck cancer patients.

The CD44 protein family consists of isoforms, encoded by standard exons and up to nine alternatively spliced variant exons (v2-v10), which are expressed in a tissue-specific way. Expression of v6-containing variants (CD44v6) has been related to aggressive behavior of various tumor types and was shown to be particularly high in squamous cell carcinoma (SCC). Therefore, CD44v6 might be a suitable target for radioimmunoscintigraphy (RIS) and therapy. The present study evaluates the novel high-affinity murine anti-CD44v6 monoclonal antibody (MAb) BIWA 1 for its safety and targeting potential in patients with SCC of the head and neck (HNSCC). Twelve HNSCC patients, who had planned to undergo resection of the primary tumor and neck dissection, were included. Preoperatively, 2, 12, or 52 mg of 99nTc-labeled MAb BIWA 1 was administered. RIS results obtained 21 h after injection were compared with palpation, computed tomography, and magnetic resonance imaging, with histopathology as the gold standard. Moreover, biodistribution of BIWA 1 was evaluated by radioactivity measurement in blood and bone marrow and in biopsies from the surgical specimen obtained 40 h after injection. The distribution of BIWA 1 in tumor biopsies was analyzed by immunohistochemistry. BIWA 1 integrity in the blood was assessed by high-performance liquid chromatography and related to soluble CD44v6 levels in serum samples. No drug-related adverse events were observed. Human antimouse antibody responses were observed in 11 patients. The diagnostic efficacy of RIS appeared to be comparable for the three BIWA 1 dose levels and for the four diagnostic methods. Besides activity uptake in tumor tissue, minimal accumulation of activity was observed in mouth, lungs, spleen, kidney, bone marrow, and scrotal area. Analysis of tissue biopsies revealed high uptake in tumors, with a mean value of 14.2+/-8.4% of the injected dose/kg tumor tissue and a mean tumor:blood ratio of 2.0+/-1.4 at 40 h after injection. Differences among the three dose groups were not statistically significant, although a trend toward lower uptake in the highest dose group was noted. Distribution of BIWA 1 throughout the tumor was heterogeneous for all dose groups, which might be related to the high affinity of the MAb. The mean biological half-life in blood (34.5+/-6.1 h) was not dose dependent. Extensive complex formation of BIWA 1 was observed in the 2-mg group, most probably with soluble CD44v6 present in the blood, and complex formation relatively diminished upon increase of the MAb dose. BIWA 1 is a promising MAb for targeting HNSCC because it can be safely administered to HNSCC patients, while it shows high and selective tumor uptake. However, BIWA 1 is immunogenic, and therefore a chimerized or humanized derivative of BIWA 1 with intermediate affinity will be used in future clinical trials.

Induction of unstable and stable chromosomal aberrations by 99mTc: in-vitro and in-vivo studies.

BACKGROUND: Biological dosimetry, which determines the dose of acquired radiation by measuring radiation-induced variation of biological parameters, can help assess radiation damage in an individual. Evaluation of radiation exposure requires setting up reference curves for each type of radiation. AIM: To evaluate the potential induction of chromosome aberrations by a clinical diagnostic dose of 99mTc. METHODS: Dicentrics, rings, excess fragments, complete reciprocal translocations and incomplete reciprocal translocations were scored in peripheral blood lymphocytes from patients exposed to a 99mTc bone scintigraphy. A specific relationship between the radiation dose delivered by 99mTc and the frequency of stable and unstable chromosomal aberrations was established in vitro to estimate whole-body dose. Chromosome analysis using fluorescence plus Giemsa and fluorescence in-situ hybridization was undertaken on six patients before and after a 99mTc bone scintigraphy. Dicentrics, rings, excess fragments, and translocations were scored in blood lymphocytes after in vitro 99mTc external irradiation in order to construct dose calibration curves. RESULTS: Analysis of the in-vitro data shows that the number of both unstable and stable aberrations has a quadratic linear relationship to the dose. Our in-vivo irradiation studies showed that activities of 99mTc-hexamethylene diphosphonate (99mTc-HDP) used for bone investigations do not induce any additional unstable chromosome aberrations and translocations. The frequencies obtained did not differ significantly from background values. CONCLUSIONS: 99mTc can produce unstable and stable chromosomal aberrations in vitro. 99mTc-HDP administration does not induce supplementary chromosomal aberrations. The dose-response curves will allow a more accurate evaluation of the risk related to in-vivo administration of 99mTc labelled radiopharmaceuticals, and they can be used to assess the safe upper limit of injected activity in humans.

A new approach for the calculation of critical organ dose in nuclear medicine applications.

The geometrical factor that is calculated to keep in mind the radiation source and detector position is rather frequently used in radiation measuring and calculating methods. In this study, using the geometrical factor is intended to suggest a new model to measure the absorbed dose in nuclear medicine applications. Therefore, the source and target organ's geometries are accepted to be disc and parallel to each other. In this manner, a mathematical model for the geometry of these discs is proposed and a disc-disc geometry factor is calculated. Theoretical calculations have been carried out with the MIRD (medical internal absorbed dose) method, which is widely used to the absorbed dose calculations in nuclear medicine. Absorbed radiation dose is separately calculated for a target organ, which is the testis, with disc-disc geometry factor model and MIRD model. Both the results are compared and the results of disc-disc geometry factor model are shown to be harmonious and acceptable with the results of MIRD model.

Radiation exposure during sentinel lymph node biopsy for breast cancer: effect on pregnant female physicians.

BACKGROUND: The radionuclide (RN) method employed for sentinel lymph node biopsy is generally safe for adult medical care workers. However, the number of pregnant medical care workers who attend surgery has recently been increasing, along with the increasing number of female surgeons. In particular, female surgeons are concerned about the position of a surgeon's lower abdominal region being close to the RN injection site. We measured the exposure dose of the lower abdominal region in medical care workers and investigated the possible exposure effect on fetuses. METHODS: A dose of (99m)Tc-phytic acid (37 MBq) was subcutaneously injected into the areola of the nipple of patients. Scintigraphy and surgery were performed after 1 and 4 h, respectively. At the time of the local injection, a personal dosimeter measured the exposure dose in the surgeon, first and second assistants, anesthesiologist, and scrub nurse. RESULTS: The median exposure doses were 3, 1, 1, 0, and 0 µSv in the surgeon, first and second assistants, anesthesiologist, and scrub nurse, respectively. Protective clothing reduced the mean exposure dose by 66 %. CONCLUSIONS: In surgeons, the exposure dose from daily life activities (1 mSv/year) corresponds to the dose received after performing 333 surgeries (using 3 µSv as the median). However, the maximum value measured was 24 µSv; at this value, the total exposure dose exceeds 1 mSV in the 42nd surgery. Medical care workers can further reduce their exposure dose by paying attention to the surgical procedure and to their posture and position.

Exposure to fingers while handling a solvent extraction-type technetium-99m generator.

Technetium-99m-labeled compounds are routinely used for various diagnostic procedures in nuclear medicine. In India, most of the nuclear medicine centers use 99mTc obtained from a solvent extraction-type generator. As a result of the long procedure involved in the separation of 99mTc from 99mMo in this type of generator compared to the elution of 99mTc from a column-type generator, the likelihood of exposure to fingers of technicians is high. The measurement of radiation exposure was done on 16 workers at seven major nuclear medicine centers in India. The maximum exposure to any of the fingers per MBq of 99mTc extracted was found to vary from 1.46 X 10(-9) to 22.38 X 10(-9) C-kg-1. With the existing work load, the exposures to the fingers were found to be within the permissible limits.

Granulomatous interstitial pneumonia in a miniature swine associated with repeated intravenous injections of Tc-99m human serum albumin: concise communication.

Albumin lung-scanning agents have a proven high degree of safety, with the only contraindication to their use being allergic hypersensitivity. We have used these agents to investigate the physiologic effects of high Gz acceleratory forces on pulmonary perfusion using the miniature swine. Multiple doses of human macroaggregated albumin and human-albumin microspheres were given to a miniature swine at various levels of centrifugal acceleration over a 6-wk period. The dosages given were the same per kilogram as those used for routine clinical human studies. The animal subsequently died from a severe granulomatous interstitial pneumonia. The granulomatous lesions suggest that the pathogenesis may have involved a cell-mediated delayed hypersensitivity. This interstitial pneumonia may represent the end point in a chronic hypersensitivity response to the human-albumin lung-scanning agents.

Adverse allergic reaction to technetium-99m methylene diphosphonate.

Adverse allergic reactions to radiopharmaceuticals are rare but have been documented in the literature. This report presents data consistent with a definite adverse reaction to the radiopharmaceutical [99mTc]MDP.

Tc-99m-PEG-Liposomes for the evaluation of colitis in Crohn's disease.

In the present study, the potential role of 99mTc-PEG-liposome to determine the extent and severity of active disease of Crohn's colitis was investigated. Patients suspected of having an exacerbation of Crohn's disease underwent a 99mTc-PEG-liposome scan (740 MBq, imaging at 4 and 24 h p.i.). A barium enema or endoscopy was performed as the standard verification procedure. Disease activity indices (Clinical Disease Activity Index and Van Hees Activity Index) were calculated. In seven patients positive images of colon segments affected by Crohn's colitis were obtained using 99mTc-PEG-liposomes. Only a moderate relation between 99mTc-liposome scan grading and verification procedures was found (Spearman rank r = 0.22). In accordance with previous studies, no significant correlation was found between the clinical disease activity indices and the verification procedures. This study was prematurely terminated because of unacceptable side-effects in 3 out of 9 patients, which occured almost immediately after starting the infusion. The complaints consisted of dyspnea and facial erythema. The symptoms were self-limiting when the infusion was stopped. In conclusion, the extent of Crohn's colitis can be established non-invasively with 99mTc-PEG-liposome scintigraphy. However, in view of the encountered side-effects, the PEG-liposomal preparation may have to be modified.