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.

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.

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.

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.

Comparison of occupational radiation exposure from myocardial perfusion imaging with Rb-82 PET and Tc-99m SPECT.

OBJECTIVE: Rubidium-82 (Rb-82) PET myocardial perfusion imaging (MPI) has superior diagnostic accuracy, at least similar prognostic value, and lower patient radiation exposure when compared with technetium-99m single-photon emission computed tomography (Tc-99m SPECT) MPI. The aim of this study was to compare occupational radiation exposure from the two modalities and show that improvements for the patient do not come at a cost to staff. MATERIALS AND METHODS: Electronic personal dosimeters were worn by staff involved in the administration and imaging of routine clinical Tc-99m SPECT and Rb-82 PET MPI, and during tracer production and QC. To estimate dose to the staff in the event of a medical emergency, a survey meter was placed in close contact with the patient during Rb-82 infusion and imaging, and immediately after administration for Tc-99m SPECT. RESULTS: Mean (SD) whole-body effective dose to staff during a single MPI procedure was 0.4 (0.4) µSv for Rb-82 PET (1110 MBq) and 3.3 (1.7) µSv for Tc-99m SPECT (350 MBq). Staff effective dose during tracer production and QC was low (<0.2 µSv/patient) and comparable between tracers. An additional effective dose was measured at close contact to the patient during, and immediately after, tracer administration, although this will not pose a significant radiation risk to staff with either technique as long as this is not routine practice. CONCLUSION: There is a significant reduction in effective dose during Rb-82 PET when compared with Tc-99m SPECT MPI because of the short half-life of Rb-82 and reduced patient contact.

On the dose calculation at the cellular level and its implications for the RBE of (99m)Tc and ¹²³I.

PURPOSE: Based on the authors' previous findings concerning the radiotoxicity of(99m)Tc, the authors compared the cellular survival under the influence of this nuclide with that following exposure to the Auger electron emitter (123)I. To evaluate the relative biological effectiveness (RBE) of both radionuclides, knowledge of the absorbed dose is essential. Thus, the authors present the dose calculations and discuss the results based on different models of the radionuclide distribution. Both different target volumes and the influence of the uptake kinetics were considered. METHODS: Rat thyroid PC Cl3 cells in culture were incubated with either(99m)Tc or (123)I or were irradiated using 200 kV x-rays in the presence or absence of perchlorate. The clonogenic cell survival was measured via colony formation. In addition, the intracellular radionuclide uptake was quantified. Single-cell dose calculations were based on Monte Carlo simulations performed using Geant4. RESULTS: Compared with external radiation using x-rays (D37 = 2.6 Gy), the radionuclides (99m)Tc (D37 = 3.5 Gy), and (123)I (D37 = 3.8 Gy) were less toxic in the presence of perchlorate. In the absence of perchlorate, the amount of activity a37 that was necessary to reduce the surviving fraction (SF) to 0.37 was 22.8 times lower for (99m)Tc and 12.4 times lower for (123)I because of the dose increase caused by intracellular radionuclide accumulation. When the cell nucleus was considered as the target for the dose calculation, the authors found a RBE of 2.18 for (99m)Tc and RBE = 3.43 for (123)I. Meanwhile, regarding the dose to the entire cell, RBE = 0.75 for (99m)Tc and RBE = 1.87 for (123)I. The dose to the entire cell was chosen as the dose criterion because of the intracellular radionuclide accumulation, which was found to occur solely in the cytoplasm. The calculated number of intracellular decays per cell was (975 ± 109) decays/MBq for (99m)Tc and (221 ± 82) decays/MBq for (123)I. CONCLUSIONS: The authors' data indicate that extra-nuclear targets to Auger electrons exist, which is obvious from our dose calculations. When considering the dose to the cell nucleus, the authors found an enhanced RBE for(99m)Tc and (123)I relative to acute x-ray irradiation and pure extracellular irradiation with both radionuclides. Surprisingly, the authors did not find any radionuclide accumulation in the cell nucleus, indicating that there are additional radiosensitive targets besides the DNA. In addition, the authors demonstrated the necessity of cellular dose calculations in radiobiological experiments using unsealed radionuclides and identified the relevant parameters.

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.

A novel device for automatic withdrawal and accurate calibration of 99m-technetium radiopharmaceuticals to minimise radiation exposure to nuclear medicine staff and patient.

A Joint Automatic Dispenser Equipment (JADE) has been designed and fabricated for automatic withdrawal and calibration of radiopharmaceutical materials. The thermoluminescent dosemeter procedures have shown a reduction in dose to the technician's hand with this novel dose dispenser system JADE when compared with the manual withdrawal of (99m)Tc. This system helps to increase the precision of calibration and to minimise the radiation dose to the hands and body of the workers. This paper describes the structure of this device, its function and user-friendliness, and its efficacy. The efficacy of this device was determined by measuring the radiation dose delivered to the hands of the nuclear medicine laboratory technician. The user-friendliness of JADE has been examined. The automatic withdrawal and calibration offered by this system reduces the dose to the technician's hand to a level below the maximum permissible dose stipulated by the international protocols. This research will serve as a backbone for future study about the safe use of ionising radiation in medicine.

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.

Pitfalls with radiopharmaceuticals.

INTRODUCTION: There is a considerable body of evidence describing that the pharmacokinetics and pharmacodynamics of radiopharmaceuticals may be changed by a variety of drugs, disease states and in some cases, surgical procedures. OBJECTIVE: : To systematically search the medical literature and review the published evidence on adverse reactions to radiopharmaceuticals. METHOD: MEDLINE, EMBASE, International Pharmaceutical Abstracts and Science Citation Index were searched for studies reporting adverse reactions to radiopharmaceuticals. Controlled trials, cohort studies, case-control studies and case series published in major Western languages were considered for the review. Each study included in the present review was described in a narrative way, and major components of each study were reported (ie, research design, patient characteristics, types of drugs and radiopharmaceuticals, dosing information and adverse reactions). RESULTS: The majority of adverse reactions to radiopharmaceuticals described in the literature required little or no treatment, and their negative effects were generally mild and self-limited. Large longitudinal greater than 5-year studies reported prevalence rates of adverse reactions due to radiopharmaceuticals ranging from 0 to 25 cases per 100,000 administrations. Case studies on the use of technetium reported mild adverse reactions; however, some led to potentially harmful complications. Similarly, studies involving fluorodeoxyglucose reported more severe adverse reactions. CONCLUSION: The literature on radiopharmaceuticals adverse effects is scarce, and just a few studies were conducted to investigate the association between radiopharmaceuticals and adverse reactions. Despite relatively mild and self-limited symptoms, the current widespread use of radiopharmaceuticals requires constant monitoring for adverse reactions.

Potential utility of radioprotective agents in the practice of nuclear medicine.

Radiopharmaceutical agents are utilized for imaging and treatment in nuclear medicine. Ionizing radiation produces free radicals in the cell that can induce damage to the DNA and lead to side-effects and/or secondary tumors. Radioprotective agents are useful in eliminating or reducing the severity of deleterious cellular effects, which are caused by exposure to internal and/or external irradiation in patients or staff personnel. There are two strategies for the potential use of radioprotective agents in patients, including agents used in patients for selective protective effects, such as reducing mocusitis, myelotoxicity, and kidney damage induced by ionizing radiation in radioiodine and radiolabeled peptide therapy. Second, radioprotective agents can reduce chromosomal aberration induced by gamma- or beta-rays and reduce the risk of tumors in personnel and patients.

Lingual thyroid.

Lingual thyroid gland is a rare clinical entity caused by failure of the gland's anlage to descend early in the course of embryogenesis. It may present with symptoms of dysphagia, upper airway obstruction, or even hemorrhage anytime from infancy through adulthood. Treatment of this disorder includes the use of exogenous thyroid hormone to correct the hypothyroidism and to induce shrinkage of the gland. When symptoms of obstruction or bleeding appear, ablative therapy by means of surgery or radioiodine is warranted. We report our experience with lingual thyroid gland and discuss elements of the diagnostic and therapeutic evaluation, with emphasis on the clinical findings, laboratory tests, and radiographic imaging studies.

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.

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.