Comparison of the radiotoxicity of the 99mTc-labeled compounds 99mTc-pertechnetate, 99mTc-HMPAO and 99mTc-MIBI.

PURPOSE: In addition to gamma radiation, 99mTc emits low-energy Auger electrons with path-lengths of nanometers to micrometers that cannot be utilized for diagnostic procedures; however, they have frequently been discussed for therapeutic applications. We compared radiotoxicity of three 99mTc-labeled radiopharmaceuticals with differences in the subcellular distribution. MATERIALS AND METHODS: The intracellular radionuclide uptake and subcellular distribution of [99mTc]-pertechnetate (99mTc-pertechnetate), [99mTc]Tc-hexamethyl-propylene-aminoxime (99mTc-HMPAO) and [99mTc]Tc-hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) were quantified in rat thyroid FRTL-5 cells. Radiotoxicity was compared using late phosphorylated histone H2AX (γH2AX) foci as a marker for unrepaired DNA double-strand breaks (DNA-DSB) and clonogenic cell survival. RESULTS: 99mTc-HMPAO showed a substantially higher uptake into the nucleus and the membrane/organelles than 99mTc-pertechnetate or 99mTc-MIBI. The colony-forming assay showed that 99mTc-pertechnetate and 99mTc-HMPAO caused a similar reduction in cell survival. 99mTc-MIBI is less radiotoxic in terms of the estimated nucleus dose and induced the fewest number of γH2AX foci compared with the other 99mTc-tracers, and 99mTc-HMPAO induced a fewer number of γH2AX foci than 99mTc-pertechnetate. CONCLUSIONS: Our findings reveal that clonogenic cellular survival is not solely determined by the DNA-DSB response. This finding may suggest the involvement of extra-nuclear radiosensitive targets in cell inactivation. For example, the mitochondria or the cell membrane could be affected by 99mTc-HMPAO.

Patient-specific dosimetry for intracavitary 32P-chromic phosphate colloid therapy of cystic brain tumours.

PURPOSE: (32)P-chromic phosphate colloid treatments of astrocytoma and craniopharyngioma cystic brain tumours in paediatric patients are conventionally based on a sphere model under the assumption of uniform uptake. The aims of this study were to determine the distribution of the absorbed dose delivered by (32)P on a patient-specific basis and to evaluate the accuracy with which this can be predicted from a pretherapy administration of (99m)Tc-Sn colloid. METHODS: Three patients were treated with (32)P-chromic phosphate colloid following (99m)Tc-Sn colloid administrations. Convolution dosimetry was performed using pretherapy and posttherapy sequential SPECT imaging, and verified with EGSnrc Monte Carlo radiation transport simulations. Mean absorbed doses to the cyst wall and dose-volume histograms were also calculated and compared with those obtained by the sphere model approach. RESULTS: Highly nonuniform uptake distributions of both the (99m)Tc and (32)P colloids were observed and characterized by dose-volume histograms to the cyst wall. Mean absorbed doses delivered to the cyst wall, obtained with the convolution method, were on average 21 % (SD 18 %) and 50 % (SD 30 %) lower than those predicted by the (99m)Tc distribution and the uniform assumption of the sphere model, respectively. CONCLUSION: Absorbed doses delivered to the cyst wall by (32)P are more accurately predicted from image-based patient-specific convolution dosimetry than from simple sphere models. These results indicate the necessity to perform personalized treatment planning and verification for intracavitary irradiation of cystic brain tumours treated with radiocolloids. Patient-specific dosimetry can be used to guide the frequency and levels of repeated administrations and would facilitate data collection and comparison to support the multicentre trials necessary to progress this therapy.

Pathophysiological premises to radiotracers for bone metastases.

Aim of our paper is to review the most important radio-compounds that can be successfully used to detect and/or characterize bone metastases. From a didactic point of view, we made a distinction between two main categories , the first allowing to individuate bone's reaction (osteotropic agents), the second trying to detect metastatic tumor cells (oncotropic agents). A wide description of the most diffuse Tc-99m diphosphonates , including analysis of uptake mechanisms and pharmacokinetics, is followed by a brief report on pathophysiological premises to the clinical use of F-18 fluoride and of specific (radioiodine, radiolabeled somatostatin or cathecolamine analogues) or non specific, as Tc-99m sestamibi, F-18 fluorodeoxhyglucose, F-18 choline, F-18 thymidine) oncotropic agents. At the end, the possibility to use diagnostic radiotracers to act both in recruiting patients with bone metastases undergoing radionuclide therapy and for their dosimetric evaluation is also discussed.

Carbohydrate conjugates for molecular imaging and radiotherapy: 99mTc(I) and 186Re(I) tricarbonyl complexes of N-(2'-Hydroxybenzyl)-2-amino-2-deoxy-D-glucose.

An approach to a new class of potential radiopharmaceuticals is demonstrated by the labeling of a glucosamine derivative with the tricarbonyls of 99mTc and 186Re. The proligand HL2 (N-(2'-hydroxybenzyl)-2-amino-2-deoxy-D-glucose) was produced by hydrogenation of the corresponding Schiff base and reacted with [NEt4]2[Re(CO)3Br3] to form the neutral complex [(L2)Re(CO)3] in 40% yield. 1H and 13C NMR spectra indicate that the [Re(CO)3] core is bound in a tridentate fashion via the amino N, phenolato O, and C-3 hydroxyl O atoms of the ligand. At the tracer-level, labeling of HL2 with [99mTc(CO)3(H2O)3]+ and [186Re(CO)3(H2O)3]+ was achieved in aqueous conditions in 95 +/- 2% and 94 +/- 3% average radiochemical yields, respectively.

Current use and future potential of organometallic radiopharmaceuticals.

Contrary to common belief, organometallic compounds exhibit remarkable stability in aerobic and even diluted aqueous solutions. Technetium-sestamibi (Cardiolite) is one of the most prominent examples of this class of compounds routinely used in nuclear medicine. This review summarises the recent progress in labelling of biomolecules with organometallic complexes for diagnostic and therapeutic application in radiopharmacy and exemplifies in detail developments focussing on organometallic technetium- and rhenium-tricarbonyl technologies. The value of such technologies has been recognised and they have become a valuable alternative to common labelling methodologies. An increasing number of groups have started to employ an organometallic precursor for the purpose of radioactive labelling of various classes of biomolecules, and the advantages and limitations of this new technique are compared with those of other labelling methods. The synthetic access to appropriate precursors via double-ligand exchange or aqueous carbonyl kit preparation for routine application is described. Strategies and examples for the design of appropriate bifunctional chelating agents for the Tc/Re-tricarbonyl core are given. The functionalization of biomolecules such as tracers for the central nervous system (dopaminergic and serotonergic), tumour affine peptides (somatostatin receptors, neuroreceptors) and tumour binding single-chain antibody fragments is summarised. Where possible and appropriate, the in vitro and in vivo results in respect of these examples are compared with those obtained with classical (99m)Tc/(188)Re(V)- and (111)In-labelled analogues. The preclinical results show the in many ways superior characteristics of organometallic labelling techniques.

Demonstration of different patterns of musculoskeletal, soft tissue and visceral involvement in melioidosis using 99m Tc stannous colloid white cell scanning.

Melioidosis is an infectious disease that can present with multiple foci of disease involvement. Assessment of disease extent can be difficult, especially in musculoskeletal, visceral and soft tissue infection. This study examined the usefulness of white cell scans in this condition. 99mTc stannous colloid white cell scanning was performed in 21 patients with culture-proven melioidosis. Scan results were compared with clinical assessment and correlated with other forms of imaging. White cell scans demonstrated all but one of the clinically apparent sites of musculoskeletal, visceral and other soft tissue infection. Unsuspected disseminated soft tissue lesions were seen in two patients, including femoral node uptake in both, and these patients subsequently presented with relapsing musculoskeletal disease. Unsuspected musculoskeletal disease was found in one patient. Clinically suspected musculoskeletal disease was accurately excluded by white cell scan in another patient. The results of white cell scanning were also examined in disease of other viscera. Renal and prostatic disease were visualized. Unsuspected parotid involvement was found in two patients. Only one of two spinal lesions was visualized. Pulmonary disease was not necessarily associated with abnormal uptake. White cell scanning is a quick and effective way of assessing the extent of musculoskeletal, visceral and soft tissue disease in melioidosis.

[Sentinel lymph node biopsy in breast cancer: a validation study and preliminary results].

INTRODUCTION: Sentinel lymph node biopsy (SLNB) has been recently proven to be an accurate staging method for breast cancer, replacing axillary lymph node dissection (ALND) in selected cases. We present our initial experience and the process of introduction and implementation of SLNB in a University Hospital setting. MATERIAL AND METHODS: 46 SLNB were performed in 42 consecutive female patients with invasive breast cancer. Treatment included 0.4mCi-2mCi of Tc-99m rhenium colloid injected either 2 hours before surgery (0.4 mCi) or the night before surgery (2 mCi). Four milliliters of Patent Blue V were injected peritumoral 10 minutes prior to skin incision in all patients. Following SLNB all women underwent subsequent ALND. Sentinel nodes were processed both with multiple (10-15) H&E sections and immunohistochemistry with cytokeratin antibodies stain. RESULTS: Blue dye, isotope or the combination of both identified 43/46 (93%) of the sentinel lymph nodes. ALND was performed only unilaterally in 4 patients with bilateral breast cancer bringing the total evaluable SLNB to 39. In the 39 patients in whom the sentinel node was successfully identified and underwent ALND, the SLNB was true positive (TP) in 17/39 (44%) true negative (TN) in 20/39 (51%) and false negative in 2/39 [(5%), both T2 lesions] with overall accuracy of 95%. In the last 10 cases all sentinel nodes were successfully identified with 70% TP and 30% TN. CONCLUSIONS: Experience with at least 30-40 consecutive cases for safe implementation of SLNB in clinical practice. Specific training and dedication is required for the entire team involved, including surgeons, nuclear medicine physicians and technicians and pathologists.

[Renoscintigraphy applied with etylenedicysteine labeled with technetium 99m and SPECT technique as a method of examining kidneys in children with vesicoureteric reflux]. / Renoscyntygrafia z zastosowaniem etylenodicysteiny znakowanej technetem 99m oraz technika SPECT jako metody badania nerek u dzieci z rozpoznanymi wstecznymi odplywami pechorzowo-moczowodowymi.

Vesicoureteric reflux (VUR) can lead to renal parenchymal damage. Renal scarring is an important cause of chronic renal failure and hypertension in children. The significance of possible effects determines the necessity of early diagnosis of urinary tract pathology. The aim of the paper was to evaluate the morphology and function of kidneys with VUR using selected radioisotope techniques, and to compare the sensitivity of planar technique and single-photon emission computed tomography (SPECT) technique in detection of renal scarring. In 45 children with VUR the following test were performed: ultrasonography, renoscintigraphy with technetium-99m-ethylenedicysteine (EC-Tc-99m) and technetium-99m-dimercaptosuccinic acid (DMSA-Tc-99m) scintigraphy with planar and SPECT mode. Stage of VUR correlates with stage of cortical lesions estimated as a value of effective renal plasma flow (ERPF) in kidney, as well as scarring intensity in static scintigraphy. The use of SPECT increases sensitivity of examination for detection small, single scars. It seems that SPECT should be used more frequently in children in the group of scarring risk. That would allow for earlier diagnosis of renal scarring, enabling efficient treatment. Due to the correlation between ERPF and parameters obtained in DMSA scintigraphy, renoscintigraphy with EC-Tc-99m may be applied to monitor the progress of renal scarring.

Pedal radiocolloid lymphoscintigraphy in demonstration of a post-surgical lymphatic leak.

Radiocolloid lymphoscintigraphy is a very effective diagnostic procedure for dynamic evaluation of lymphatic flow. In this case report, the use of radiocolloid lymphoscintigraphy in detection of a post-surgical lymphatic leak is presented. Dynamic pedal lymphoscintigraphy with Tc 99m-antimony trisulfide colloid clearly demonstrated the site of the leak.