Bone Seeking Research Articles

Bone-seeking tumor cells alter bone material quality parameters on the nanoscale in mice

Bone metastases related to breast and prostate cancer present with multiple challenges and skeletal related events like fragility fractures impair the quality of life of the patients significantly. To determine local alterations in bone material quality with bone metastasis, we subjected murine tibial specimens, generated after intratibial injections of either RM-1 prostate cancer cells or EO771 breast cancer cells into male and female mice respectively, to high-resolution imaging modalities. Small and wide-angle X-ray scattering showed unaltered mineral characteristics in the more osteosclerotic prostate cancer model, while the quantification of calcium weight percentage via backscattered electron microscopy determined minor differences along the perilacunar bone matrix. Further analyses of mineral and collagen characteristics were performed using Raman spectroscopy and focused ion beam electron microscopy. Our study indicates that alterations in nanochannel properties occur due to the presence of bone seeking tumor cells with more prevalent nanopores in the perilacunar matrix.

Development of [64Cu]Cu-BPAMD for PET imaging of bone metastases

Abstract In this study, preclinical evaluation and dosimetric estimation of [64Cu]Cu-BPAMD, as a new bone-seeking agent for PET imaging, was studied. [64Cu]Cu-BPAMD was produced with a specific activity of 8.7 GBq/µmol and radiochemical purity (R.P.) of >98 %. The HA binding results showed the binding of nearly all [64Cu]Cu-BPAMD complex to HA at about 15 mg. Biodistribution studies in the male Syrian rats indicated considerable accumulation in the bone with negligible uptake in the other organs. The bone surface and the bone marrow receiving 0.199 and 0.092 mGy/MBq, respectively, are the organs with the most absorbed dose. This study confirms the production of [64Cu]Cu-BPAMD with high R.P. showing high potential for PET-imaging of bone metastases. The lower absorbed dose of mainly human organs compared to 68Ga-BPAMD can be considered one of the advantages of this new radiolabeled compound.

Nonosseous bone seeking tracer focal uptake in the conventional scintigraphy.

Nonosseous bone seeking tracer focal uptake in the conventional scintigraphy.

Attacking the Achilles heel of cardiac amyloid nuclear scintigraphy: How to reduce equivocal and false positive studies

BackgroundPlanar and single-photon emission computed tomography (SPECT) nuclear imaging techniques with bone seeking radiotracers have been increasingly adopted for diagnosis of ATTR cardiac amyloidosis. However, inherent limitations of these techniques due to lack of anatomical landmarks have been recognized, with consequent high numbers of equivocal or false positive cases. SPECT/computed tomography (CT) fusion imaging offers a significant advantage to overcome these limitations by substantially reducing inaccurate interpretations. The authors present the results of a 3-year imaging quality improvement project that focused on reducing the high number of equivocal studies that were noted in the first two years of the amyloidosis program, comparing SPECT only to SPECT/CT fusion technique. MethodsA retrospective, systematic analysis of 176 patient records was performed to test the premise that SPECT/CT fusion imaging has the potential to reduce equivocal and false positive results. ResultsOf a total of 176 patients, 35 equivocal (19.8%), 32 (18.18%) strongly suggestive, and 109 (61.93%) not suggestive cases were identified. Recognizing that this was not consistent with the international data, the authors set out on a comprehensive quality assessment project to reduce the number of equivocal and false positive cases. In patients who initially underwent SPECT only (Group A; n = 78), the addition of SPECT/CT fusion resulted in the net reclassification of 73% of cases: 100% of equivocal cases (n = 35) were reclassified to not suggestive (n = 34) or strongly suggestive (n = 1). 73% of strongly suggestive cases (n = 30) were reclassified to not suggestive (n = 22) while 8 strongly suggestive cases were confirmed as true positives. 13 not suggestive cases remained negative after SPECT/CT fusion. In cases where SPECT/CT fusion was utilized from the beginning (Group B; n = 98), there were no reclassification of any of the cases when these cases were reprocessed as a control group. ConclusionAddition of SPECT/CT imaging reduces the false positive or equivocal studies and increases the diagnostic accuracy of the test. All false positive and equivocal studies were eliminated using the fusion technique. Utilizing the fusion imaging technique increases the spatial resolution, with the ability to localize myocardial uptake and accurately differentiate from blood pool, which is a major source of error.

Urinary Bladder Carcinoma Demonstrated on Bone Scintigraphy and SPECT/CT Images.

Bone scintigraphy with Tc-99m-diphosphonate analogs are widely used in staging, restaging, and monitoring the therapy effectiveness of various cancer types. Bone-seeking agents are excreted through urination, resulting in the visualization of either anatomical abnormalities or pathological conditions of the kidneys and bladder. We present a case of a 63-year-old man with urinary bladder carcinoma depicted on whole body planar and single-photon emission computed tomography/computed tomography images.

SPECT/CT SUV-based metrics: A promising diagnostic tool in classifying patients with suspected transthyretin cardiac amyloidosis among the different Perugini grades?

The purpose of this study was to evaluate the contribution of single photon emission computed tomography/computed tomography (SPECT/CT) standardized uptake value (SUV) metrics in classifying patients with suspected transthyretin cardiac amyloidosis (ATTR-CA) among the different Perugini grades. One hundred four patients suspected of ATTR-CA underwent planar scintigraphy with bone seeking tracer (99mTc pyrophosphate-PYP). Patients were classified according to the Perugini scale, the H/CL, H/Bone and H/Bkg ratios. A subset of 48 patients received additional SPECT/CT. Single photon emission computed tomography/CT SUV quantitative parameters, of the heart, myocardium, lungs, liver, soft tissues, bone, and SUV ratios (SUVmaxmyo, SUVmaxlungs, SUVmaxliver, SUVmaxbone and SUVmaxsoft tissue ratios), were evaluated in order to investigate potential metrics that could more clearly differentiate Perugini grades. A total of 33.7% of patients were considered grade 0, 34.6% grade 1 and 31.7% grade 2/3. A combination of H/CL >1.33 and H/Bone >0.85 showed the highest sensitivity 100%. Standardized uptake value-based metrics clearly differentiated grade 0 or 1 vs grades 2 or 3, whereas no significant difference was found between grades 0 and 1, or between grades 1 and 2. The combined cut-off values H/CL 1.33 and SUVmaxmyo 2.88 yielded 100% sensitivity and 84.6% specificity in differentiating ATTR-CA positives vs negatives. The metric SUVmaxmyo/SUVmaxliver was the best metric to classify patients with grade 1 as negative (grade 0) or positive (grade 2 or 3). Single photon emission computed tomography/CT SUV metrics could be complementary to planar scintigraphy in classifying patients among the different Perugini grades. The ratio SUVmaxmyo/SUVmaxliver was the only parameter with high affinity to differentiate patients with grade 1, as grade 0 or grade 2/3 for ATTR-CA.

Equine skeletal scintigraphy: Comparing normal bone-to-soft tissue ratio 2 and 4 hours after injection with either hydroxymethylene diphosphonate ormethylene diphosphonate.

In equine skeletal scintigraphy, there is no information about the possible influence of different phosphonate compounds on image quality. This prospective randomised study determined bone uptake changes and image quality for hydroxymethylene diphosphonate (HDP) and methylene diphosphonate (MDP) in equine patients at different time points. Scintigraphic images of the radius and the tibia of 20 horses were acquired at 2 and 4 hours after injection of either technetium-labelled HDP or MDP. Three regions of interest were identified-in the bone diaphysis, adjacent soft tissue and background area-to determine the normal bone-to-soft tissue ratio (BSR). Qualitative analysis was performed using a modified scoring system. In terms of BSR and count rates, HDP showed a slightly better incorporation into bone compared to MDP, but significant differences were only detected for count rates at 4 hours after injection (p = 0.048). The radiopharmaceutical used did not influence qualitative image scoring, which was correlated with the BSR (ρ = 0.49; p ≤ 0.001). The choice of HDP or MDP for equine skeletal scintigraphy does not seem to substantially affect BSR and qualitative image scoring. Further studies with a larger sample size, including the evaluation of lesion detection ability for both bone-seeking agents, are needed.

Multimodality Imaging in the Diagnosis and Assessment of Cardiac Amyloidosis.

Amyloidosis is a rare disorder where abnormal protein aggregates are deposited in tissues forming amyloid fibrils, leading to progressive organ failure. Although any organ can be affected, cardiac involvement is the main cause of morbidity and mortality associated with amyloidosis as diagnosis is often delayed due to the indolent nature of the disease in some forms. An early diagnosis of disease and knowledge of the type/subtype of cardiac amyloidosis (CA) are essential for appropriate management and better outcome. Echocardiography is often the first line of investigation for patients suspected of CA and offers superior hemodynamic assessment. Although cardiovascular magnetic resonance (CMR) imaging is not diagnostic of CA, it provides vital clues to diagnosis and has a role in disease quantification and prognostication. Radiolabeled bone seeking tracers are the mainstay of diagnosis of CA and when combined with screening of monoclonal light chains, bone scintigraphy offers high sensitivity in diagnosing transthyretin type of CA. This review aims to describe the noninvasive imaging assessment and approach to diagnosis of patients with suspected CA. Imaging features of echocardiography, nuclear scintigraphy, and CMR are described with a brief mention on computed tomography.

Novel 99mTc labeled complexes with bisphosphonate isocyanide: Radiosynthesis and evaluation as potential bone-seeking agents

In order to develop 99mTc-labeled complexes with bisphosphonate isocyanide as novel bone imaging agents, two bisphosphonate isocyanide derivatives (CNALN and CNPAM) were synthesized and radiolabeling was performed for preparing the corresponding [99mTc]Tc(I) complexes. [99mTc]Tc-CNALN and [99mTc]Tc-CNPAM were obtained with high radiochemical purity and showed good in vitro stability. Both of them were hydrophilic and had high affinity to hydroxyapatite. The biodistribution studies in mice revealed [99mTc]Tc-CNALN showed higher bone/background ratios at 60 min post-injection. In single photon emission computed tomography (SPECT) imaging study, [99mTc]Tc-CNALN had an obvious accumulation in bone, suggesting it would be a promising bone-seeking agent.

P290 CARDIAC AMYLOIDOSIS, A CHALLENGING DIAGNOSTIC WORK – UP

Abstract A 79 years–old male presented to our outpatient clinic with symptoms of an initial heart failure. He had an history of atrial fibrillation (AF), anaemia and thrombocytopaenia, which have never been deeply investigated, bilateral carpal tunnel syndrome. Electrocardiogram (EKG) showed AF with normal ventricular rate and low peripherical QRS voltages. Laboratory testing was significant for NT proBNPelevation, pancytopenia and iron overload. An echocardiogram (ECHO) was done showing a hypokinetic and dilated biventricular cardiopathy. The therapy was therefore optimized with clinical benefit. At coronary angiography a severe stenosis of left coronary artery was observed with normal myocardial perfusion imaging. Cardiovascular magnetic resonance (CMR) excluded an iron intramyocardial overload (in contrast to the hepatic and splenic parenchyma) and detected a subendocardial pattern of LGE at lateral and mid–basal septal area. Emochromatosis and Gaucher disease were excluded. As suggested by hematologists, he underwent osteomedullary biopsy (OMB) and a myelodysplastic syndrome (MDS) was diagnosed. He was still symptomatic for dyspnea on mild exertion. The following ECHO revealed normal left ventricular (LV) size with moderate concentric remodeling, mildly impaired LV systolic function and LV filling pattern suggestive of restrictive cardiomyopathy. All these data prompted suspicion for an infiltrative cardiopathy. Nuclear scintigraphy with the use of bone seeking agent was done and showed Perugini grade 2 cardiac uptake. Moreover, amyloid deposits were identified after Congo red–staining from OMB. immunoglobulin light chain (LA) amyloidosis was excluded. Conclusion based on the above findings, Cardiac Amyloidosis TTR–related wild type was diagnosed. The diagnosis of MDS and the identification of iron overload were incidental findings. The patient, currently in follow up at our center, is a candidate to Tafamidis.

Development of self-powered multifunctional piezomagnetic nanoparticles for non-invasive post-surgical osteosarcoma theranogeneration

Non-invasive treatment approaches are gaining increased attention in recent times due to the potential improvement in treatment efficiency. Here we report a brand-new ultrasound (US), magnetic field (MF), and light responsive nanoparticle system based on piezoelectric barium titanate and superparamagnetic iron oxide nanoparticles termed as PiezoMagnetic nanoparticles (PMNPs) for the multimodal anticancer treatment, complimentary imaging, and non-invasive cell stimulation. Systematic electrical studies reveal that PMNPs exhibit superior ferroelectric and conducting properties and produce electrical signals analogous to native tissues when mechanically stimulated and using Food and Drug Administration (FDA) approved Low intensity Pulsed Ultrasound (LIPUS) non-invasively for cell stimulation. The green energy generation from PMNPs are further proved by the real-time demonstration of commercial LED lit-up. Thus, as a proof of concept, we have demonstrated a stepwise treatment efficacy of PMNPs for the post-surgical osteosarcoma therapy, diagnosis, and regeneration (termed as Theranogeneration). The PMNPs exhibited excellent anticancer properties to eradicate the residual osteosarcoma cells by magnetic hyperthermia, photothermal and photodynamic therapy along with complimentary imaging capabilities as X-ray computed tomography contrast agent and label free fluorescent probe. The conjugation of risedronate R (RIS)- a new generation bisphosphonates to PMNPs imparted bone seeking property to PMNPs. Therefore, as a result of noninvasive cell stimulation properties of PMNPs under LIPUS and LIPUS mediated RIS release from PMNPs resulted in enhanced bone regeneration and bone turnover which helps to repair the large bone defects occurs in osteosarcoma resection. Thus, the study corroborates the development of a potential bioactive piezoelectric nanoplatform that can be used to control the cell behaviour and fate in order to develop new types of therapies for multiple diseases including various types of cancers in remotely controlled approaches.

Difference Uptake of 99mTc-Pyrophosphate vs 99mTc- Methylenediphosphate in Detecting Cardiac Amyloidosis; First Experience in Hasan Sadikin General Hospital

Cardiac amyloidosis (CA) is a disorder caused by deposits of insoluble fibrils in the myocardium and an underdiagnosed cause of heart failure. Immunoglobulin Light Chain-Associated Amyloid (AL) and Amyloidosis Transthyretin-related (ATTR) are the two protein precursors that most commonly cause cardiac amyloidosis. It is important to distinguish between these two types of amyloidosis because the treatment and prognosis of each types is different. Recent advances in cardiac radionuclide imaging, in particular using bone-seeking agents such as 99mTc-Pyrophosphate (PYP) and 99mTc-Methylenediphosphate (MDP), can differentiate AL from ATTR. This study aimed was to investigate the uptake characteristic of both tracers in CA. Three patients with suspected of having cardiac amyloidosis underwent two cardiac radionuclide imaging examinations using those two different radiopharmaceuticals. The cardiac images were analyzed quantitatively and semi-quantitatively based on ASNC (American Society of Nuclear Medicine) criteria. Cardiac radioactivity uptake of 99mTc-PYP was better from those of 99mTc-MDP based on quantitative as well as semi-quantitative (visual assessment).
 Keywords: cardiac amyloidosis; cardiac imaging; 99mTc-PYP; 99mTc-MDP

Update on imaging in chronic kidney disease-mineral and bone disorder: promising role of functional imaging.

Disorders of mineral metabolism and bone disease are common complications in chronic kidney disease (CKD) patients and are associated with increased morbidity and mortality. Bone biopsies, bone scintigraphy, biochemical markers, and plain films have been used to assess bone disorders and bone turnover. Of these, functional imaging is less invasive than bone/marrow sampling, more specific than serum markers and is therefore ideally placed to assess total skeletal metabolism. 18F-sodium fluoride (NaF) PET/CT is an excellent bone-seeking agent superior to conventional bone scan in CKD patients due to its high bone uptake, rapid single-pass extraction, and minimal binding to serum proteins. Due to these properties, 18F-NaF can better assess the skeletal metabolism on primary diagnosis and following treatment in CKD patients. With the increased accessibility of PET scanners, it is likely that PET scanning with bone-specific tracers such as 18F-NaF will be used more regularly for clinical assessment and quantitation of bone kinetics. This article describes the pattern of scintigraphic/functional appearances secondary to musculoskeletal alterations that might occur in patients with CKD.

Synthesis, Complexation Properties, and Evaluation of New Aminodiphosphonic Acids as Vector Molecules for 68Ga Radiopharmaceuticals.

Two new aminodiphosphonic acids derived from salicylic acid and its phosphonic analogue were prepared through a simple and efficient synthesis. 2-[(2-Amino-2,2-diphosphono)ethyloxy]-benzoic acid 8 and 2-[(2-amino-2,2-diphosphono)ethyloxy]-5-ethyl-phenylphosphonic acid 9 were evaluated for their applicability as 68Ga binding bone-seeking agents. Protonation constants of 8 and 9 and stability constants of the Ga3+ complexes with 8 and 9 in water were determined. The stability constant of Ga3+ complex with fully phosphorylated acid 9 (logKGaL = 31.92 ± 0.32) significantly exceeds stability constant of Ga3+ complex with 8 (logKGaL = 26.63 ± 0.24). Ligands 8 and 9 are as effective for Ga3+ cation binding as ethylenediamine-N,N’-diacetic-N,N’-bis(methy1enephosphonic) acid and ethylenediamine-N,N,N’,N’-tetrakis(methylenephosphonic) acid, respectively. The labelling process and stability of [68Ga]Ga-8 and [68Ga]Ga-9 were studied. Both 8 and 9 readily form 68Ga-complexes stable to ten-fold dilution with saline. However, in fetal bovine serum, only [68Ga]Ga-9 was stable enough to be subject to biological evaluation. It was injected into rats with bone pathology and aseptic inflammation of soft tissues. For [68Ga]Ga-9 in animals with a bone pathology model in 60 and 120 min after injection, a slight accumulation in the pathology site, stable blood percentage level, and moderate accumulation in the liver were observed. For animals with an aseptic inflammation, the accumulation of [68Ga]Ga-9 in the pathology site was higher than that in animals with bone pathology. Moreover, the accumulation of [68Ga]Ga-9 in inflammation sites was more stable than that for [68Ga]Ga-citrate. The percentage of [68Ga]Ga-9 in the blood decreased from 3.1% ID/g (60 min) to 1.5% ID/g (120 min). Accumulation in the liver was comparable to that obtained for [68Ga]Ga-citrate.

Clinical Perspectives of Theranostics.

Theranostics is a precision medicine which integrates diagnostic nuclear medicine and radionuclide therapy for various cancers throughout body using suitable tracers and treatment that target specific biological pathways or receptors. This review covers traditional theranostics for thyroid cancer and pheochromocytoma with radioiodine compounds. In addition, recent theranostics of radioimmunotherapy for non-Hodgkin lymphoma, and treatment of bone metastasis using bone seeking radiopharmaceuticals are described. Furthermore, new radiopharmaceuticals for prostatic cancer and pancreatic cancer have been added. Of particular, F-18 Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography (PET) is often used for treatment monitoring and estimating patient outcome. A recent clinical study highlighted the ability of alpha-radiotherapy with high linear energy transfer (LET) to overcome treatment resistance to beta--particle therapy. Theranostics will become an ever-increasing part of clinical nuclear medicine.

Complexation of Scandium with Oxabis(ethylenenitrilo)tetramethylenephosphonic Acid and Applicability of Its 44Sc-Labelled Analogue as Bone-Seeking Agent

The regularities of complexation of scandium with oxabis(ethylenenitrilo)tetramethylenephosphonic acid (OBEP), which is actively used nowadays in the clinical practice for the synthesis of bone-seeking radiopharmaceuticals, have been studied by means of potentiometric titration and NMR spectroscopy. The stability constant of the deprotonated complex (log β110 = 20.25 ± 0.74, 0.1 M NaClO4, 25°C) and the pH range of effective binding of scandium to OBEP (3 to 9) have been found comparable to these of similar lanthanide complexes. The possibility of efficient synthesis of [44Sc]Sc–OBEP complexes without an isotopic carrier with radiochemical purity of at least 98% has been shown. Preliminary evaluation of the applicability of [44Sc]Sc–OBEP complex as a bone-seeking radiopharmaceutical for PET visualization of metabolic skeletal lesions has been performed. The accumulation of [44Sc]Sc–OBEP in the bone lesion has been found to be 3.0–3.5 times higher than that in the intact bone.

Rhabdomyolysis following coronary angiography: an unexpected detection on 99mTc-methyl diphosphonate bone scintigraphy

BackgroundBone scintigraphy is an appropriate tool in the management of cancers for the detection of bone metastasis. Technetium 99 m-methylene diphosphonate (99mTc-MDP) is commonly used as a bone-seeking agent. The bones take up 99mTc-MDP through a process called chemisorption, which is more evident in areas of increased osteoblastic activities. Nevertheless, extra-osseous 99mTc-MDP uptake is an infrequent occurrence, which warrants a thorough clinical assessment to evaluate such findings. An example of extraosseous uptake discovery is rhabdomyolysis, which requires prompt recognition and immediate management. Rhabdomyolysis secondary to an adverse reaction towards iodinated contrast material is a rare condition that warrants a high index of clinical suspicion.Case presentationWe present a case of a 75-year-old gentleman with underlying benign prostatic hypertrophy, and chronic kidney disease who had undergone a coronary angiography examination and intervention for ischemic heart disease. Pre-scheduled bone scintigraphy with 99mTc-MDP for the work-up of raised serum prostate-specific antigen (PSA) was performed 2 weeks post coronary angiography examination. Whole-body bone scan with single-photon emission computed tomography/computed tomography (SPECT/CT) images showed an unexpected finding of extensive extra-osseous uptake in the muscles and soft tissues. Additional investigations confirmed the diagnosis of rhabdomyolysis. Nevertheless, despite the prompt recognition, administration of treatment and supportive care, the patient succumbed to life-threatening complications.ConclusionThis case highlights the importance of recognising and identifying the pattern of extra-osseous uptake on bone scintigraphy imaging to ensure early intervention of severe and life-threatening conditions such as rhabdomyolysis.

A case of cardiac amyloidosis incidentally detected by bone scintigraphy.

A 73-year-old man with lung cancer underwent bone scintigraphy for disease staging. Diffuse myocardial technetium hydroxymethylene diphosphonate (99mTc-HMDP) uptake was incidentally found. A diagnosis of amyloid transthyretin (ATTR) cardiac amyloidosis was suspected, although the patient had no symptoms at this time. Single-photon emission computed tomography (SPECT) showed particularly strong uptake in the ventricular septum. Cardiac magnetic resonance imaging (CMR) showed widespread subendocardial and partly transmural enhancement of the left ventricular myocardium on delayed postcontrast T1-weighted images. These findings were consistent with ATTR cardiac amyloidosis. 18F-FDG uptake in the left ventricle wall was observed on PET/CT. He was finally diagnosed with ATTR by endomyocardial biopsy. There are two major subtypes of cardiac amyloidosis: ATTR amyloidosis and amyloid light-chain (AL) amyloidosis. Endomyocardial biopsy is the gold standard for diagnosis. Recently, however, several reports have shown that bone scintigraphy using a 99mTc-labelled bone-seeking agent can detect ATTR cardiac amyloidosis and differentiate it from AL amyloidosis. Bone scintigraphy may play an important role in the detection and differentiation of ATTR cardiac amyloidosis.

Person-specific calibration of a partial body counter used for individualised Am241 skull measurements

Incorporation of bone seeking alpha-emitting radionuclides such as 241Am are of special concern, due to the potential of alpha particles to damage the extremely radiation-sensitive bone marrow. In the case of an internal contamination with 241Am, direct in vivo measurements using Gamma-detectors are typically used to quantify the incorporated activity. Such detectors need to be calibrated with an anatomical phantom, for example of the skull, of known 241Am activity that reproduces the anatomy of the measured individual as closely as possible. Any difference in anatomy and material composition between phantom and individual will bias the estimation of the incorporated activity. Consequently, in this work the impact of the most important anatomical parameters on detection efficiency of one of the germanium detectors of the Helmholtz Center Munich (HMGU) partial body counter were systematically studied. For that a detailed model of the germanium detector was implemented in the Monte Carlo codes GEANT4 and MCNPX. To simulate the detector efficiency, various skull voxel phantoms were used. By changing the phantom dimensions and geometry the impact of parameters such as shape and size of the skull, thickness of tissue covering the skull bone, distribution of 241Am across the scull and within the skull bone matrix, on the detector efficiency was studied. Approaches to correct for these parameters were specifically developed for three physical skull phantoms for which Voxel phantoms were available: Case 102 USTUR phantom, Max-06 phantom, BfS phantom. Based on the impact of each parameter, correction factors for an ‘individual-specific’ calibration were calculated and applied to a real 241Am contamination case reported in 2014. It was found that the incorporated 241Am activity measured with the HMGU partial body counter was about twice as large as that estimated when using the BfS skull phantom without applying any correction factor for person-specific parameters. It is concluded that the approach developed in the present study should in the future be applied routinely for skull phantom measurements, because it allows for a considerably improved reconstruction of incorporated 241Am using partial body counters.

68Ga-Labeled bismacrocyclic methylene phosphonate as potential bone seeking PET radiopharmaceutical

Phosphonates-based agents are well-known bone-seeking radiopharmaceuticals with application in detection and therapy. With higher sensitivity and resolution offered by Positron Emission Tomography (PET), tracers based on this technique are gaining huge attention. 68Ga-based generator and radiotracers render independence from the on-site cyclotron. We report the development of 68Ga-labeled DOTA-based bismacrocyclic phosphonate derivative, for bone PET imaging. The synthesis and characterization of 68Ga- DO3P-AME-DO3P was carried out in > 95% purity. The radiotracer displayed high stability and low binding affinity (<3%) to blood serum. High in vitro binding affinity were observed for synthetic hydroxyapatite, SAOS-2, osteoclast and osteoblast cells. In vivo pharmacokinetics revealed fast washout with biphasic release pattern. The deposition of radiotracer in osseous tissues was high (Bone/Muscle ratio:18), as studied from the biodistribution studies. In vivo PET/CT and biodistribution analyses revealed the ability of 68Ga-DO3P-AME-DO3P to target and accumulate in bone, thus displaying its potential as a PET bone imaging agent.