Radionuclide Injection Research Articles

Radionuclide shuntography for cerebrospinal fluid shunt flow evaluation in adults.

Radionuclide shuntography (RS) performed using 99mTc-DTPA injected into the reservoir of CSF shunts enables evaluation of CSF flow for suspected shunt malfunctions. The goal of this study was to report the authors' institutional experience with RS and evaluate its utility and associated complications. The authors retrospectively reviewed all RS studies performed between November 2003 and June 2022. Patients with shunted hydrocephalus who were ≥ 18 years of age were included. Patients undergoing RS for evaluation of Ommaya reservoirs were excluded. Demographics, hydrocephalus etiology, presenting symptoms, study results, subsequent management, complications, and intraoperative diagnoses were recorded. Chi-square tests were reported for categorical variables and standard 2 × 2 contingency methods were used for sensitivity/specificity analysis. The authors identified 211 RS procedures performed in 142 patients. The mean age at procedure was 55.6 ± 20.9 years (mean ± SD). Normal pressure hydrocephalus was the most common hydrocephalus etiology (37.0%), followed by congenital malformations (26.1%) and idiopathic intracranial hypertension (15.6%). Successful radionuclide injection was achieved in 207 studies (98.1%). Shunt patency was confirmed in 63.8% of successful injections, whereas malfunction was demonstrated in 27.1% and abnormally slow flow was seen in 9.2%. RS studies demonstrating shunt malfunction were more likely to result in subsequent revisions than were studies showing patency (86.6% vs 2.9%; p < 0.0001). The overall sensitivity and specificity of RS for detecting shunt malfunction was 92.3% and 96.2%, respectively. The median follow-up time was 29 months, with 151 cases having ≥ 6 months of follow-up. There were no complications or infections attributable to RS in this cohort. RS is a useful and safe tool in the workup of shunt malfunction.

Current status of optoacoustic breast imaging and future trends in clinical application: is it ready for prime time?

Optoacoustic imaging (OAI) is an emerging field with increasing applications in patients and exploratory clinical trials for breast cancer. Optoacoustic imaging (or photoacoustic imaging) employs non-ionizing, laser light to create thermoelastic expansion in tissues and detect the resulting ultrasonic emission. By combining high optical contrast capabilities with the high spatial resolution and anatomic detail of grayscale ultrasound, OAI offers unique opportunities for visualizing biological function of tissues in vivo. Over the past decade, human breast applications of OAI, including benign/malignant mass differentiation, distinguishing cancer molecular subtype, and predicting metastatic potential, have significantly increased. We discuss the current state of optoacoustic breast imaging, as well as future opportunities and clinical application trends. CLINICAL RELEVANCE STATEMENT: Optoacoustic imaging is a novel breast imaging technique that enables the assessment of breast cancer lesions and tumor biology without the risk of ionizing radiation exposure, intravenous contrast, or radionuclide injection. KEY POINTS: • Optoacoustic imaging (OAI) is a safe, non-invasive imaging technique with thriving research and high potential clinical impact. • OAI has been considered a complementary tool to current standard breast imaging techniques. • OAI combines parametric maps of molecules that absorb light and scatter acoustic waves (like hemoglobin, melanin, lipids, and water) with anatomical images, facilitating scalable and real-time molecular evaluation of tissues.

Clinical effectiveness and safety of intraarticular administration of a 117m Tin radiocolloid (Synovetin OATM ) for treatment of early and intermediate grade osteoarthritis of the elbow in a dose finding study conducted in 44 dogs.

Osteoarthritis of the elbow joint secondary to elbow dysplasia is common in dogs. Intraarticular radionuclide injection is thought to suppress both synovitis and inflammatory pain mediators in the joint which are not directly addressed by current treatments. This dose-finding investigation was a longitudinal, prospective, experimental parallel group, post-test study with repeated measures. Forty-four dogs, with low to intermediate-grade osteoarthritis, received a single injection into their most clinically affected elbow joint and were randomized into three treatment cohorts; 37 MBq, 64.75 MBq, or 92.5 MBq (normalized to the body surface area of a 22 kg dog) of 117m Sn radiocolloid. Dogs were assessed monthly by owners, using the canine Brief Pain Inventory (cBPI), and at 1, 3, 6, 9, and 12 months intervals by investigators. Positive responses to treatment were observed by both owners and clinicians in all dose groups with the medium dose group having the highest and most durable response rate based on cBPI scores. The results of this study support the use of 117m Sn radiocolloid as a primary treatment of osteoarthritis in low to intermediate-grade osteoarthritis of the canine elbow.

Glypican-3-Targeted 227Th α-Therapy Reduces Tumor Burden in an Orthotopic Xenograft Murine Model of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a significant cause of morbidity and mortality worldwide, with limited therapeutic options for advanced disease. Targeted α-therapy is an emerging class of targeted cancer therapy in which α-particle-emitting radionuclides, such as 227Th, are delivered specifically to cancer tissue. Glypican-3 (GPC3) is a cell surface glycoprotein highly expressed on HCC. In this study, we describe the development and invivo efficacy of a 227Th-labeled GPC3-targeting antibody conjugate (227Th-octapa-αGPC3) for treatment of HCC in an orthotopic murine model. Methods: The chelator p-SCN-Bn-H4octapa-NCS (octapa) was conjugated to a GPC3-targeting antibody (αGPC3) for subsequent 227Th radiolabeling (octapa-αGPC3). Conditions were varied to optimize radiolabeling of 227Th. In vitro stability was evaluated by measuring the percentage of protein-bound 227Th by γ-ray spectroscopy. An orthotopic athymic Nu/J murine model using HepG2-Red-FLuc cells was developed. Biodistribution and blood clearance of 227Th-octapa-αGPC3 were evaluated in tumor-bearing mice. The efficacy of 227Th-octapa-αGPC3 was assessed in tumor-bearing animals with serial measurement of serum α-fetoprotein at 23 d after injection. Results: Octapa-conjugated αGPC3 provided up to 70% 227Th labeling yield in 2 h at room temperature. In the presence of ascorbate, at least 97.8% of 227Th was bound to αGPC3-octapa after 14 d in phosphate-buffered saline. In HepG2-Red-FLuc tumor-bearing mice, highly specific GPC3 targeting was observed, with significant 227Th-octapa-αGPC3 accumulation in the tumor over time and minimal accumulation in normal tissue. Twenty-three days after treatment, a significant reduction in tumor burden was observed in mice receiving a 500 kBq/kg dose of 227Th-octapa-αGPC3 by tail-vein injection. No acute off-target toxicity was observed, and no animals died before termination of the study. Conclusion:227Th-octapa-αGPC3 was observed to be stable invitro; maintain high specificity for GPC3, with favorable biodistribution invivo; and result in significant antitumor activity without significant acute off-target toxicity in an orthotopic murine model of HCC.

Glioma Biopsy Based on Hybrid Dual Time-Point FET-PET/MRI-A Proof of Concept Study.

Neuroimaging based on O-[2-(18F)fluoroethyl]-l-tyrosine (FET)-PET provides additional information on tumor grade and extent compared with MRI. Dynamic PET for biopsy target selection further improves results but is often clinically impractical. Static FET-PET performed at two time-points may be a good compromise, but data on this approach are limited. The aim of this study was to compare the histology of lesions obtained from two challenging glioma patients with targets selected based on hybrid dual time-point FET-PET/MRI. Five neuronavigated tumor biopsies were performed in two difficult cases of suspected glioma. Lesions with (T1-CE) and without contrast enhancement (T1 and T2-FLAIR) on MRI were selected. Dual time-point FET-PET imaging was performed 5–15 min (PET10) and 45–60 min (PET60) after radionuclide injection. The most informative FET-PET/MRI images were coregistered with MRI in time of biopsy planning. Five biopsy targets (three from high uptake and two from moderate uptake FET areas) thought to represent the most malignant sites and tumor extent were selected. Histopathological findings were compared with FET-PET and MRI images. Increased FET uptake in the area of non-CE locations on MRI correlated well with high-grade gliomas localized as far as 3 cm from T1-CE foci. Selecting a target in the motor cortex based on FET kinetics defined by dual time-point PET resulted in a grade IV diagnosis after previous negative biopsies based on MRI. An additional grade III diagnosis was obtained from an area of glioma infiltration with moderate FET uptake (between 1 and 1.25 SUV). These findings seem to show that dual time-point FET-PET-based biopsies can provide additional and clinically useful information for glioma diagnosis. Selection of targets based on dual time-point images may be useful for determining the most malignant tumor areas and may therefore be useful for resection and radiotherapy planning.

One of the earliest refractory inclusions and its implications for solar system history

A ∼175 µm refractory inclusion, A-COR-01 from one of the least altered carbonaceous chondrites, ALHA 77307 (CO3.0), has been found to bear unique characteristics that indicate that it is one of the first solids to have formed at the very birth of the solar system while isotopic reservoirs were still evolving rapidly. Its core is composed mainly of hibonite and corundum, the two phases predicted to condense first from a gas of solar composition, and like many common types of Calcium-, Aluminium-rich Inclusions (CAIs) is surrounded by a rim of diopside.Core minerals in A-COR-01 are very 16O-rich (Δ17OCore = −32.5 ± 3.3 (2SD) ‰) while those in the rim display an O isotopic composition (Δ17ORim = −24.8 ± 0.5 (2SD) ‰) indistinguishable from that found in the vast majority of the least altered CAIs. These observations indicate that this CAI formed in a very 16O-rich reservoir and either recorded the subsequent evolution of this reservoir or the transit to another reservoir. The origin of A-COR-01in a primitive reservoir is consistent with the very low content of excess of radiogenic 26Mg in its core minerals corresponding to the inferred initial 26Al/27Al ratio ((26Al/27Al)0 = (1.67 ± 0.31) × 10−7), supporting a very early formation before injection and/or homogenisation of 26Al in the protoplanetary disk. Possible reservoir evolution and short-lived radionuclide (SLRs) injection scenarios are discussed and it is suggested that the observed isotope composition resulted from mixing of a previously un-observed early reservoir with the rest of the disk.

Radiation Doses and Risks in Breast Screening.

This article describes radiation doses and cancer risks of digital breast imaging technologies used for breast cancer detection. These include digital mammography (DM), digital breast tomosynthesis (DBT), and newer technologies such as contrast-enhanced digital or spectral mammography (CEM), whole-breast computed tomography, breast-specific gamma imaging (BSGI), molecular breast imaging (MBI), and positron emission mammography (PEM). This article describes the basis for radiation risk estimates, compares radiation doses and risks, and provides benefit-to-radiation-risk ratios for different breast imaging modalities that use ionizing radiation. Current x-ray-based screening modalities such as DM and DBT have small to negligible risks of causing radiation-induced cancers in women of normal screening age. Possible new screening modalities such as CEM have similar small cancer risks. Potential screening modalities that involve radionuclide injection such as BSGI, MBI, and PEM have significantly higher cancer risks unless efficient detection systems and reduced administered doses are used. Benefit-to-radiation-risk estimates are highly favorable for screening with DM and other modalities having comparable (or higher) cancer detection rates and comparably low radiation doses.

External radiation exposure rate after18F-FDG PET/CT examination

18F fluorodeoxyglucose (FDG) is widely used for PET CT examinations; however, positron-emitting florin generates relatively high gamma radiation (511 keV) raising occupational as well as public safety concerns. This study aimed to measure the rate of radiation emitted from patients that underwent18FDG PET/CT examination for oncological conditions, approximately 2 hours after the procedure, before and after urination. A total of 100 patients who underwent18F-FDG PET/CT examination were included in this study. Following imaging, external radiation exposure rate was measured using proportional counter probe at 1-m distance, approximately 2 hours after the completion of imaging procedure, before and after urination. Factors effecting resulting exposure from patients were examined. The mean post-urination activity ranged between 0.2 and 6.3 μSv/h (median, 1.8 μSv/h). Presence of metastasis, tumor type and gender did not have any effect on mean post-urination activity (P&gt;0.05 for all comparisons). Older age, greater BMI and higher administered dose were associated with higher post-urination activity (P &lt; 0.05 for all comparisons). Findings of this study showed that 2 hours after radionuclide injection, activity rate from patients is far below the recommended limits for general population and further decreases after urination. Discharging patients at 2 hours after urination would not seem to pose radiation health risk for relatives, public or other hospital staff.

Human sodium iodide transporter gene-mediated imaging and therapy of mouse glioma, comparison between 188Re and 131I.

Novel treatment options are urgently required for patients with glioma who are not effectively treated through standard therapy. Human sodium iodide symporter (hNIS) is a molecular target of certain tumors types. Compared with 131I, 188Re possesses a higher energy and shorter half-life; therefore, the effects of 188Re and 131I were compared in hNIS-mediated gene imaging and therapy in the present study. Recombinant human brain glioma cell line U87 was transfected with a recombinant lentiviral vector containing hNIS (U87-hNIS). U87-0 cell line transfected with blank lentivirus was prepared as a control. In vitro, the 188Re and 131I uptake of U87-hNIS cells were 21.3-times and 25.9-times that of the control groups, however the excretion rate of the two nuclides was very rapid, and the half-life was only ~4 min. Sodium perchlorate inhibited hNIS-mediated 188Re and 131I uptake to levels observed in the control groups. 188Re and 131I were able to kill U87-hNIS cells selectively, with a survival of only 21.6 and 36.2%, respectively. U87-hNIS nude mice appeared to accumulate 188Re, with a ratio of radioactivity counts between tumor and non-tumor sites of ~13.5 compared with 10.3 of 131I 1 h after radionuclide injection. In contrast with in vitro studies, U87-hNIS cells demonstrated a notable increase in 188Re retention in vivo, even 24 h after 188Re injection. U87-hNIS cells also exhibited increased 131I retention in vivo; however, as the time increased, 131I was rapidly released with the tumor no longer able to be imaged 24 h after 131I injection. Following treatment, U87-hNIS tumors experienced a volume reduction of 24.1%, whereas U87-0 cells demonstrated an increase of 28.8%. 188Re and 131I were revealed to be effective at decreasing tumor volume compared with the control. However, 188Re was significantly more potent compared with 131I (P<0.01). The present study indicated that the U87-hNIS cell line is sufficient to induce specific 188Re and 131I uptake, which may kill cells in vitro and in vivo. 188Re exhibited an increased retention time in vivo compared with 131I, which facilitates the imaging and therapy of U87-hNIS tumors.

Make visible palpable, a “double-insurance strategy” for nodule localization

Localization for tiny pulmonary nodule during video-assisted thoracoscopic surgery (VATS) approach to facilitate sublobar resection remains a challenge for thoracic surgeons. To look for a needle in a haystack, adjuvant techniques such as hookwire insertion, colour dye or radionuclide injection have been well reported (1). However, such traditional techniques require a patient being transferred from the radiographic suite for localization and the operation room for resection, which would lead to more substantial complications, for example, pleuritic pain, label or marking migration, and pneumothorax to mention just a few.

Pre-irradiation tumour volumes defined by MRI and dual time-point FET-PET for the prediction of glioblastoma multiforme recurrence: A prospective study

Background and purposeThe diagnostic accuracy of magnetic resonance imaging (MRI) for glioblastoma multiforme (GBM) is suboptimal. We analysed pre-treatment MRI- and dual time-point 18F-fluoroethylthyrosine-PET (FET-PET)-based target volumes and GBM recurrence patterns following radiotherapy with temozolomide. Materials and methodsThirty-four patients with primary GBM were treated according to MRI-based treatment volumes (GTVRM). Patients underwent dual time-point FET-PET scans prior to treatment, and biological tumour volumes (GTVPET) were contoured but not used for target definition. Progressions were classified based on location of primary GTVs. Volume and uniformity of MRI- vs. FET-PET/CT-derived GTVs and progression patterns assessed by MRI were analysed. ResultsFET-based GTVs measured 10min after radionuclide injection (a.r.i.; median 37.3cm3) were larger than GTVs measured 60min a.r.i. (median 27.7cm3). GTVPET volumes were significantly larger than corresponding MRI-based GTVs. MRI and PET concordance for the identification of glioblastoma GTVs was poor (mean uniformity index 0.4). 74% of failures were inside primary GTVPET volumes, with no solitary progressions inside the MRI-defined margin +20mm but outside the GTVPET detected. ConclusionsThe size and geometry of GTVs differed in the majority of patients. The GTVPET volume depends on time after radionuclide injection. FET-PET better defined failure site than MRI alone.

Predicting standard-dose PET image from low-dose PET and multimodal MR images using mapping-based sparse representation

Positron emission tomography (PET) has been widely used in clinical diagnosis for diseases and disorders. To obtain high-quality PET images requires a standard-dose radionuclide (tracer) injection into the human body, which inevitably increases risk of radiation exposure. One possible solution to this problem is to predict the standard-dose PET image from its low-dose counterpart and its corresponding multimodal magnetic resonance (MR) images. Inspired by the success of patch-based sparse representation (SR) in super-resolution image reconstruction, we propose a mapping-based SR (m-SR) framework for standard-dose PET image prediction. Compared with the conventional patch-based SR, our method uses a mapping strategy to ensure that the sparse coefficients, estimated from the multimodal MR images and low-dose PET image, can be applied directly to the prediction of standard-dose PET image. As the mapping between multimodal MR images (or low-dose PET image) and standard-dose PET images can be particularly complex, one step of mapping is often insufficient. To this end, an incremental refinement framework is therefore proposed. Specifically, the predicted standard-dose PET image is further mapped to the target standard-dose PET image, and then the SR is performed again to predict a new standard-dose PET image. This procedure can be repeated for prediction refinement of the iterations. Also, a patch selection based dictionary construction method is further used to speed up the prediction process. The proposed method is validated on a human brain dataset. The experimental results show that our method can outperform benchmark methods in both qualitative and quantitative measures.

Lymphatic transit rate as a novel predictive parameter for nodal metastasis in primary truncal skin cancers.

Prediction of nodal metastasis in skin cancer before sentinel lymph node (SLN) biopsies is ideal to avoid unnecessary SLN biopsy performance. Primary truncal skin cancers are characterized by the lymphatic flow that drains from the primary lesion, occasionally to plural nodal basins. The scintigraphic appearance time (SAT), defined as the time between radionuclide injection and first SLN visualization, can potentially predict nodal metastasis, and a short SAT is a predictive parameter for metastasis. We recently introduced a novel method to measure the lymphatic flow rate using dynamic lymphoscintigraphy exhibiting a time-activity curve in the SLN. The time at which the count reaches a plateau in the SLN is termed the scintigraphic saturation time (SST) and can be a good alternative to the SAT. Moreover, the value obtained by division of the distance between the primary lesion and the SLN by the SST was termed the lymphatic transit rate (LTR), which represents the scintigraphic saturation velocity. In the present study, we evaluated LTR as a predictive parameter for nodal metastasis. Data for 22 lymph nodes from 18 patients with primary truncal skin cancers were used. Histopathologically, nodal metastasis was determined in nine nodes of eight patients. Because the mean LTR were 1.84cm/min in non-metastatic SLN and 2.38cm/min in metastatic SLN, the LTR was significantly higher in metastatic SLN than in non-metastatic SLN. All SLN with LTR of less than 1.8cm/min were histopathologically evaluated as non-metastatic. The LTR may be a predictive indicator for nodal metastasis.

Visualization of Gallbladder with In-111 Octreotide Scan.

A 54-year-old woman underwent octreotide scintigraphy for evaluation of neuroendocrine tumor recurrence. The images demonstrated unusual uptake in gallbladder area in addition to physiologic uptake at other tissues. Whole-body planar and SPECT imaging were repeated after fatty meal ingestion at 28 hours in order to figure out whether this activity was physiologic or not. Since the unusual uptake in the gallbladder was still detected at these images, additional images were obtained 72 hours after radionuclide injection. The activity in the gallbladder disappeared at these images revealing the physiologic nature of this unusual accumulation.

The Value of Sentinel Lymph Node Biopsy in Oral Cavity Cancers.

The aim of this study was to establish the effectiveness of sentinel lymph node biopsy in the detection of metastasis in N0 necks of T1-T2 early-stage oral cavity cancers. Twenty neck dissections were performed in 18 patients diagnosed with T1 and T2 oral cavity cancer, with an indication for elective neck dissection between November 2007 and January 2011. The male to female ratio was 12:8, with a mean age of 54.5 years (range 28-76). Eight of the dissections were performed for lower lip cancer, 7 for tongue cancer, and 5 for floor of the mouth cancer. Sentinel lymph node biopsy was used to detect metastatic lymph nodes. Tc99m radionuclide injection was administered to the periphery of the tumor 24 h before the operation, and a lymphoscintigraphy image was obtained 30 min after the injection. Sentinel lymph nodes were localized and excised on the day of surgery using static lymphoscintigraphy images and a gamma probe. Sentinel lymph nodes were sent for a frozen section examination, and either a selective or a comprehensive neck dissection was performed for each neck according to the results. After the final histopathological examination of the specimens, the negative predictive value, the positive predictive value, the accuracy of the sentinel lymph node biopsy, and frozen section accuracy were found to be 100%. Sentinel lymph node biopsy was found to be an efficient method in the pathological staging and management of the N0 neck in early T-stage oral cavity cancers.

Regadenoson Versus Dipyridamole Hyperemia for Cardiac PET Imaging

ObjectivesThe goal of this study was to compare regadenoson and dipyridamole hyperemia for quantitative myocardial perfusion imaging. BackgroundRegadenoson is commonly used for stress perfusion imaging. However, no study in nuclear cardiology has employed a paired design to compare quantitative hyperemic flow from regadenoson to more traditional agents such as dipyridamole. Additionally, the timing of regadenoson bolus relative to tracer administration can be expected to affect quantitative flow. MethodsSubjects underwent 2 rest/stress cardiac positron emission tomography scans using an Rb-82 generator. Each scan employed dipyridamole and a second drug in random sequence, either regadenoson according to 5 timing sequences or repeated dipyridamole. A validated retention model quantified absolute flow and coronary flow reserve. ResultsA total of 176 pairs compared regadenoson (126 pairs, split unevenly among 5 timing sequences) or repeated dipyridamole (50 pairs). The cohort largely had few symptoms, only risk factors, and nearly normal relative uptake images, with 8% typical angina or dyspnea, 20% manifest coronary artery disease, and a minimum quadrant average of 80% (interquartile range: 76% to 83%) on dipyridamole scans. Hyperemic flow varied among regadenoson timing sequences but showed consistently lower stress flow and coronary flow reserve compared with dipyridamole. A timing sequence most similar to the regadenoson package insert achieved about 80% of dipyridamole hyperemia, whereas further delaying radiotracer injection reached approximately 90% of dipyridamole hyperemia. Because of the small numbers of pairs for each regadenoson timing protocol and a paucity of moderate or large perfusion defects, we did not observe a difference in relative uptake. ConclusionsWith the standard timing protocol from the package insert, regadenoson achieved only 80% of dipyridamole hyperemia quantitatively imaged by cardiac positron emission tomography using Rb-82. A nonstandard protocol using a more delayed radionuclide injection after the regadenoson bolus improved its effect to 90% of dipyridamole hyperemia.

Measurement of cutaneous lymphatic flow rates in patients with skin cancer: area extraction method.

Some recent reports have revealed that the long scintigraphic appearance time (SAT), defined as the time between radionuclide injection and first sentinel lymph node (SLN) visualization in lymphoscintigraphy, is a negative predictive parameter of nodal metastasis in patients with melanoma. However, most of the methods used to measure the SAT were ambiguous because they utilized visualization in lymphoscintigraphy. We herein introduce a novel method by which to measure the SAT and lymphatic flow rate. The data of 33 patients with primary skin cancer were used. Sequential images were obtained using dynamic lymphoscintigraphy, and a time-activity curve of the SLN was created. The time at which the counts reached plateau was newly defined as an alternative to the SAT and was termed the scintigraphic saturation time (SST). The figure obtained by division of the distance by the SST was newly defined as an alternative to the lymphatic flow rate and termed the lymphatic transit rate (LTR). The SST was clearly determined. It ranged from 220 to 1430 s (mean, 805 s). Pathological examination revealed nodal metastasis in five patients. In 28 patients without metastasis, the mean LTR was in the order of lower limbs (4.07 ± 0.35 cm/min), upper limbs (2.67 ± 0.33 cm/min), trunk (1.79 ± 0.47 cm/min), and head and neck (1.11 ± 0.22 cm/min). The LTRs were higher in patients with nodal metastasis than those without. This method may be effective for accurate measurement of the SAT and lymphatic flow rate.

SU‐E‐T‐256: Optimizing the Combination of Targeted Radionuclide Therapy Agents Using a Multi‐Scale Patient‐Specific Monte Carlo Dosimetry Platform

Purpose:Combination targeted radionuclide therapy (TRT) is appealing because it can potentially exploit different mechanisms of action from multiple radionuclides as well as the variable dose rates due to the different radionuclide half‐lives. The work describes the development of a multiobjective optimization algorithm to calculate the optimal ratio of radionuclide injection activities for delivery of combination TRT.Methods:The ‘diapeutic’ (diagnostic and therapeutic) agent, CLR1404, was used as a proof‐of‐principle compound in this work. Isosteric iodine substitution in CLR1404 creates a molecular imaging agent when labeled with I‐124 or a targeted radiotherapeutic agent when labeled with I‐125 or I‐131. PET/CT images of high grade glioma patients were acquired at 4.5, 24, and 48 hours post injection of 124I‐CLR1404. The therapeutic 131I‐CLR1404 and 125ICLR1404 absorbed dose (AD) and biological effective dose (BED) were calculated for each patient using a patient‐specific Monte Carlo dosimetry platform. The optimal ratio of injection activities for each radionuclide was calculated with a multi‐objective optimization algorithm using the weighted sum method. Objective functions such as the tumor dose heterogeneity and the ratio of the normal tissue to tumor doses were minimized and the relative importance weights of each optimization function were varied.Results:For each optimization function, the program outputs a Pareto surface map representing all possible combinations of radionuclide injection activities so that values that minimize the objective function can be visualized. A Pareto surface map of the weighted sum given a set of user‐specified importance weights is also displayed. Additionally, the ratio of optimal injection activities as a function of the all possible importance weights is generated so that the user can select the optimal ratio based on the desired weights.Conclusion:Multi‐objective optimization of radionuclide injection activities can provide an invaluable tool for maximizing the dosimetric benefits in multi‐radionuclide combination TRT.BT, JG, and JW are affiliated with Cellectar Biosciences which owns the licensing rights to CLR1404 and related compounds.

Single photon emission computed tomography imaging for temporal dynamics of thyroidal and salivary radionuclide accumulation in 17-allyamino-17-demothoxygeldanamycin-treated thyroid cancer mouse model

Selective iodide uptake and prolonged iodine retention in the thyroid is the basis for targeted radioiodine therapy for thyroid cancer patients; however, salivary gland dysfunction is the most frequent nonthyroidal complications. In this study, we have used noninvasive single photon emission computed tomography functional imaging to quantify the temporal dynamics of thyroidal and salivary radioiodine accumulation in mice. At 60 min post radionuclide injection, radionuclide accumulation in the salivary gland was generally higher than that in thyroid due to much larger volume of the salivary gland. However, radionuclide accumulation per anatomic unit in the salivary gland was lower than that in thyroid and was comparable among mice of different age and gender. Differently, radionuclide accumulation per anatomic unit in thyroid varied greatly among mice. The extent of thyroidal radioiodine accumulation stimulated by a single dose of exogenous bovine TSH (bTSH) in triiodothyronine (T₃)-supplemented mice was much less than that in mice received neither bTSH nor T₃ (nontreated mice), suggesting that the duration of elevated serum TSH level is important to maximize thyroidal radioiodine accumulation. Furthermore, the extent and duration of radioiodine accumulation stimulated by bTSH was less in the thyroids of the thyroid-targeted RET/PTC1 (thyroglobulin (Tg)-PTC1) mice bearing thyroid tumors compared with the thyroids in wild-type (WT) mice. Finally, the effect of 17-allyamino-17-demothoxygeldanamycin on increasing thyroidal, but not salivary, radioiodine accumulation was validated in both WT mice and Tg-PTC1 preclinical thyroid cancer mouse model.

Characterization of an Orbital Melanoma and Mucosa Associated Lymphoid Tissue (MALT) Lymphoma by Dual Phase N-Isopropyl-p-I-123 Iodoamphetamine

Usefulness of N-isopropyl-p-I-123 iodoamphetamine (I-123 IMP) for the detection of malignant melanoma and malignant lymphoma is well known. The appropriate interval from administration until image acquisition is unusual because the accumulation mechanism is different. We present a case of choroidal melanoma of the right orbit with a history of low-grade mucosa-associated lymphoid tissue lymphoma of the left lacrimal gland. She was followed with magnetic resonance imaging and dual phase I-123 IMP imaging 3 times. Viability of the melanoma was estimated by I-123 IMP delayed image obtained 24 hours after intravenous injection. In spite of cryosurgery twice, the accumulation of the tracer remained unchanged. Subsequent tumor excision proved the lesion to be a viable malignant melanoma. On the other hand, posttherapeutic mucosa-associated lymphoid tissue lymphoma of the left lacrimal gland was followed by the early image obtained 20 minutes after radionuclide injection. The accumulation increased gradually and the recurrence was pointed out. In the same way, magnetic resonance imaging examination was undertaken 3 times. Both lesions were obvious, but the findings were entirely unchanged in each examination.