Tumor-seeking Agent Research Articles

Evaluation of tumor viability in Post radiation therapy pediatric brain tumors with 99mTc- glucoheptonate single photon emission computed tomography (SPECT)

Brain single photon emission computed tomography (SPECT) with 99mTc- glucoheptonate, a blood brain barrier imaging agent, is rapidly regaining interest after it has been shown that the uptake of tumor seeking agents like thallium, tetrofosmin, sestamibi and pertechnate by brain tumors is solely dependent on disruption of the blood brain barrier. Therefore, the use of 99mTc glucoheptonate may yield the same diagnostic information as other agents such as the much more expensive 99mTc-sestamibi. The purpose of the study was to evaluate 99mTc-glucoheptonate as an imaging agent for recurrent primary brain tumors in children. Methods: Fifty-one patients aged 5-18 years were evaluated for tumor recurrence following radiotherapy for primary malignant brain tumors, using brain single photon emission computed tomographies (SPECT) with 99mTc-Glucoheptonate. Contrast enhanced computerized tomography (CT) of brain was performed in all patients within + 1 week of brain SPECT as a diagnostic standard and compared. Results: Recurrent tumors showed avid 99mTc- glucoheptonate concentration and a high 99mTc-glucoheptonate retention index (6.06 + 1.41) compared with post radiation gliosis, which showed no 99mTc-glucoheptonate concentration over the affected site and had a 99mTc-glucoheptonate retention index of 1.10 + 0.18 (p=0.001). 99mTc- glucoheptonate SPECT had a sensitivity of 79.48% and a specificity of 91.66% when compared with contrast-enhanced computed tomography as a gold standard. However, this technique did not show good performance in the differential diagnosis of lesions in posterior fossa. Conclusion: This study suggests that 99mTc-glucoheptonate brain SPECT can be used as a sensitive and specific diagnostic test to differentiate recurrent tumor from post radiation gliosis, with the exception of tumors located in posterior fossa. Further studies should address this limitation before definite protocols are established.

Untiring Pursuit for Glucarate-Based Molecular Imaging Probes.

Glucarate, a physiologic end-product of the D-glucuronic acid pathway in mammals, is a six-carbon dicarboxylic acid with a wide range of uses. Glucarate-based molecular imaging probes including [99mTc]glucarate and [18F]glucarate have been developed and demonstrated to have infarct/necrosis-avid and/or tumor-seeking properties, showing potential applications in early detection of myocardial infarction, evaluation of tissue viability, monitoring of therapeutic effectiveness, and noninvasive imaging of certain tumors including drug-resistant ones. The mechanism by which [99mTc]glucarate localizes in acute necrotic tissues has been demonstrated to be largely attributable to its binding to the positively charged histones, which become accessible after the disruption of the cell and nuclear membranes as a result of irreversible damage, while the tumor-seeking mechanism of [99mTc]glucarate has been found to be closely related to glucose transporter 5 expression. Moreover, the recently developed [18F]glucarate provides a new alternative probe for positron emission tomography imaging and may have potential advantages over [99mTc]glucarate. In this review, we present the untiring pursuit for glucarate-based molecular imaging probes as infarct/necrosis-avid agent and/or tumor-seeking agent. Moreover, the limitations and the prospects for future research of glucarate-based molecular probes are also discussed.

A Model In Vitro Study Using Hypericin: Tumor-Versus Necrosis-Targeting Property and Possible Mechanisms

Hypericin (Hyp) had been explored as a tumor-seeking agent for years; however, more recent studies showed its necrosis-avidity rather than cancer-seeking property. To further look into this discrepancy, we conducted an in vitro study on Hyp retention in vital and dead cancerous HepG2 and normal LO2 cell lines by measuring the fluorescence intensity and concentration of Hyp in cells. To question the DNA binding theory for its necrosis-avidity, the subcellular distribution of Hyp was also investigated to explore the possible mechanisms of the necrosis avidity. The fluorescence intensity and concentration are significantly higher in dead cells than those in vital cells, and this difference did not differ between HepG2 and LO2 cell lines. Hyp was taken up in vital cells in the early phase and excreted within hours, whereas it was retained in dead cells for more than two days. Confocal microscopy showed that Hyp selectively accumulated in lysosomes rather than cell membrane or nuclei. Hyp showed a necrosis-avid property rather than cancer-targetability. The long-lasting retention of Hyp in dead cells may be associated with halted energy metabolism and/or binding with certain degraded cellular substrates. Necrosis-avidity of Hyp was confirmed, which may be associated with halted energy metabolism in dead LO2 or HepG2 cells.

THE ROLE OF TUMOR-SEEKING RADIOPHARMACEUTICALS IN THE DIAGNOSIS AND MANAGEMENT OF ADRENAL TUMORS.

The variety of tumor-seeking radiopharmaceuticals, which are currently in clinical use, may have a potential role as imaging agents for adrenal gland tumors, due to physiological characteristics of this organ. The purpose of this study was to evaluate the diagnostic potential of 99mTc-HYNIC-TOC, 99mTc(V)-DMSA, and 99mTc-MIBI in the assessment of adrenal tumors, by correlating with imaging findings and histopathologic results. The research is designed as a cross-sectional prospective study. The study included 50 patients with adrenal tumors (19 hormone-secreting and 31 nonfunctioning) and 23 controls without adrenal involvement. In all patients, single-photon emission computed tomography (SPECT) was performed, using qualitative and semiquantitative analysis. The tumor to non-tumor tracer uptake was conducted by using a region-of-interest technique. Adrenal to background (A/B) ratio was calculated in all cases. 99mTc-HYNIC-TOC scintigraphy showed a high statistical significance between A/B ratios, while other two tracers resulted in a lower sensitivity, specificity and accuracy. Futhermore, 99mTc-HYNIC-TOC could have a high diagnostic yield to detect adrenal tumors (the receiver-operating-characteristic curve analysis, A/B ratio cut-off value of 8.40). A semiquantitative SPECT analysis showed that 99mTc-HYNIC-TOC is a highly sensitive tumor-seeking agent for the accurate localization of adrenal tumors.

Clinical usefulness of 99mTc-HYNIC-TOC, 99mTc(V)-DMSA, and 99mTc-MIBI SPECT in the evaluation of pituitary adenomas

BackgroundThe aim of this study was to evaluate the behavioral uptake and ability to diagnose pituitary adenoma (PA) using tumor-seeking radiopharmaceuticals, and to provide a semiquantitative analysis of tracer uptake in the pituitary region.Patients and methodsThe study included 33 (13 hormonally active and 20 nonfunctioning) patients with PA and 45 control participants without pituitary involvement. All patients (n=78) underwent single photon emission computed tomography (SPECT) imaging with technetium-99m-labeled hydrazinonicotinyl-tyr3-octreotide (99mTc-HYNIC-TOC), dimercaptosuccinic acid (99mTc(V)-DMSA) and hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI). A semiquantitative analysis of abnormal uptake was carried out by drawing identical regions of interest over the pituitary area and the normal brain on one transverse section that shows the lesion most clearly. The pituitary uptake to normal brain uptake (P/B) ratio was calculated in all cases.ResultsThe result of this study confirms that the SPECT semiquantitative method, with all three tracers, showed statistically significant differences between the PA group and the controls. However, 99mTc-HYNIC-TOC scintigraphy could have the highest diagnostic yield because of the smallest overlap between the P/B ratios between adenoma versus nonadenoma participants (the receiver operating characteristic curve P/B ratio cut-off value was 13.08). In addition, only 99mTc-MIBI SPECT have the diagnostic potential to detect secreting PAs, with statistically significant differences between groups (P<0.001), with an receiver operating characteristic curve P/B ratio cut-off value of 16.72.ConclusionA semiquantitative analysis of increased focal tracer uptake in the sellar area showed that 99mTc-HYNIC-TOC is a highly sensitive and reliable tumor-seeking agent for detecting PA, whereas 99mTc-MIBI SPECT is a highly sensitive and specific method in differentiating hormone-secreting pituitary tumor.

To study the efficacy of thallium-201 as tumor seeking agent and to study its role in therapeutic response

BackgroundTumour seeking characteristics of TL-201 have been underutilized. The study was undertaken to evaluate the role of TL-201 scintigraphy in tumour imaging. MethodsA total of 50 cases were studied over a period of 18 months (13 lymphomas, 11 breast carcinoma, 10 lung cancer, 6 of soft tissue sarcoma, 2 bone tumours and 4 cases each of thyroid and brain tumours). Thallium-201 chloride was injected IV in the dose range of 3–5mCi. Imaging was done using Siemen's ECAM dual headed gamma camera. Mean tumour to background ratio (T/B ratio) was calculated for all the positive cases. Descriptive statistical analysis was carried out. ResultsFindings revealed a sensitivity of 94.12%, specificity 87.5%, PPV 94.12%, NPV 87.50% and accuracy of 92% for TL-201 tumour imaging. The mean T/B ratio for the true positive cases at 10min and at 3h was 1.81 and 1.99 respectively, the difference being 0.18 (P value <0.001). Amongst them, the mean T/B ratios for low-grade tumours were 1.45±0.32 at 10min and 1.63±0.38 after 3h with difference of 0.176 (P<0.001). For the high-grade tumours the ratios were 2.08±0.35 and 2.26±0.41 respectively with a difference of 0.186 (P<0.001). ConclusionThallium-201 scintigraphy is a useful tumour imaging modality in cases of thyroid, breast, brain, lung, soft tissue and bone tumours and lymphomas. A T/B ratio of 1.63±0.38 in 3h-delayed imaging is suggestive of low-grade tumours. For high-grade tumours a ratio of 2.26±0.41 should be considered significant.

Design optimization and performances of an intraoperative positron imaging probe for radioguided cancer surgery

Extent and accuracy of surgical resection is a crucial step in operable tumor therapy. Emergence of promising specific tumor-seeking agents labeled with positron emitters is giving rise to a renewed interest for radioguided surgery using beta probes. Beta detection, due to the particle short range, allows a more sensitive and accurate tumor localization compared to gamma radiotracers. In that context, we are currently developing an intraoperative positron imaging probe using SiPM photosensors to perform tumor localization and post-operative control of the surgical cavity. Because compactness is a key feature when trying to detect positron emitters with high sensitivity in small surgical cavities, we chose to study the simplest detector design based on the use of a very thin organic scintillator coupled to the photosensor. Different designs of the positron imaging probe, including scintillator material and thickness, light spreading window and optical reflector, were investigated with Monte-Carlo simulations and measurements. Their impact on the probe performances were optimized in terms of positron sensitivity, gamma rays background noise contamination, spatial resolution and bias and uniformity. The ability of the probes to detect small radiolabeled tumors was also investigated by simulating different phantom uptake configurations.

The role of technetium Tc99m-tetrofosmin as head and neck tumor-seeking agent: a preliminary report

The role of technetium Tc99m-tetrofosmin as head and neck tumor-seeking agent: a preliminary report

Evaluation of Tl-201 SPECT imaging findings in prostate cancer

To compare with histopathological findings the findings of prostate cancer imaging by SPECT method using Tl-201 as a tumor seeking agent. The study comprised 59 patients (age range 51-79 years, mean age 65.3 ± 6.8 years) who were planned to have transrectal ultrasonography (TRUS)-guided biopsies due to suspicion of prostate cancer between April 2011 and September 2011. Early planar, late planar and SPECT images were obtained for all patients. Scintigraphic evaluation was made in relation to uptake presence and patterns in the visual assessment and to Tumor/Background (T/Bg) ratios for both planar and SPECT images in the quantitative assessment. Histopathological findings were compatible with benign etiology in 36 (61%) patients and malign etiology in 23 (39%) patients. Additionally, comparisons were made to evaluate the relationships between uptake patterns,total PSA values and Gleason scores. A statistically significant difference was found between the benign and malignant groups in terms of uptake in planar and SPECT images and T/Bg ratios and PSA values. No statistically significant difference was found between uptake patterns of planar and SPECT images and Gleason scores in the malignant group. SPECT images were superior to planar images in the comparative assessment. Tl-201 SPECT imaging can provide an additional contribution to clinical practice in the diagnosis of prostate cancer and it can be used in selected patients.

Assessment of 99mTc-MIBI SPECT(/CT) to monitor multidrug resistance-related proteins and apoptosis-related proteins in patients with ovarian cancer: a preliminary study

Multidrug resistance (MDR) has been suggested to be a major cause of failure of chemotherapy treatment for cancer. It is associated with the expression of MDR-related and apoptosis-related proteins. Recently, technetium-99m hexakis 2-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been suggested as a tumor-seeking agent for the detection of MDR. The aim of this study was to evaluate (99m)Tc-MIBI single-photon emission computed tomography (SPECT)(/CT) for functional imaging of MDR-related and apoptosis-related proteins in patients with ovarian cancer. Eleven women (mean age 63 years, range 53-76) with a clinical suspicion of ovarian cancer were prospectively studied. All patients were examined with (99m)Tc-MIBI imaging before surgery. After intravenous injection of 740 MBq (99m)Tc-MIBI, SPECT(/CT) imaging at 10 min and 2 h was performed. Based on the semiquantitative analysis of (99m)Tc-MIBI SPECT(/CT), both early and delayed tumor uptake ratios and washout rate % were calculated. The expression of MDR-related and apoptosis-related proteins was assessed in surgically excised tumors. Immunohistochemical staining was performed to quantify the expression levels of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein1 (MRP1), MRP3, lung resistance protein (LRP), breast cancer resistance protein (BCRP), Y-box-binding protein-1 (YB-1), Bcl-2, Bax and glutathione-S-transferase. (99m)Tc-MIBI imaging results and immunohistochemical results were compared. Laparotomy was performed in all patients. Six ovarian cancers were proven by histopathological examination. Five of the six ovarian cancers were positive for (99m)Tc-MIBI uptake on both early and delayed images with (99m)Tc-MIBI SPECT(/CT). MDR-related and apoptosis-related proteins were found to be expressed in all tumors. For the five positive (99m)Tc-MIBI uptake cases, the washout rate % of (99m)Tc-MIBI uptake showed a significant positive correlation with the expression of YB-1 (r = 0.988, P = 0.0015), and the early tumor uptake ratio showed a significant positive correlation with the expression of Bax (r = 0.882, P = 0.047). Our results suggested that (99m)Tc-MIBI SPECT(/CT) might be a valuable diagnostic imaging technique to evaluate MDR-associated YB-1 and Bax-mediated apoptosis in patients with ovarian cancer.

Transcriptional response of BALB/c mouse thyroids following in vivo astatine-211 exposure reveals distinct gene expression profiles

BackgroundAstatine-211 (211At) is an alpha particle emitting halogen with almost optimal linear energy transfer for creating DNA double-strand breaks and is thus proposed for radionuclide therapy when bound to tumor-seeking agents. Unbound 211At accumulates in the thyroid gland, and the concept of basal radiation-induced biological effects in the thyroid tissue is, to a high degree, unknown and is most valuable.MethodsFemale BALB/c nude mice were intravenously injected with 0.064 to 42 kBq of 211At, resulting in absorbed doses of 0.05 to 32 Gy in the thyroid gland. Thyroids were removed 24 h after injection; total RNA was extracted from pooled thyroids and processed in triplicate using Illumina MouseRef-8 Whole-Genome Expression Beadchips.ResultsThyroids exposed to 211At revealed distinctive gene expression profiles compared to non-irradiated controls. A larger number of genes were affected at low absorbed doses (0.05 and 0.5 Gy) compared to intermediate (1.4 Gy) and higher absorbed doses (11 and 32 Gy). The proportion of dose-specific genes increased with decreased absorbed dose. Additionally, 1.4 Gy often exerted opposite regulation on gene expression compared to the other absorbed doses. Using Gene Ontology data, an immunological effect was detected at 0.05 and 11 Gy. Effects on cellular response to external stress and cell cycle regulation and proliferation were detected at 1.4 and 11 Gy.ConclusionsConclusively, the cellular response to ionizing radiation is complex and differs with absorbed dose. The response acquired at high absorbed doses cannot be extrapolated down to low absorbed doses or vice versa. We also demonstrated that the thyroid - already at absorbed doses similar to those obtained in radionuclide therapy - responds with expression of a high number of genes. Due to the increased heterogeneous irradiation at low absorbed doses, we suggest that this response partly originates from non-irradiated cells in the tissue, i.e., bystander cells.

Incidental Detection of a Benign Thymoma on Tc-99m MIBI Myocardial Perfusion Study

Technetium-99m methoxy-isobutylisonitrile (Tc-99m MIBI) is a routinely used radiopharmaceutical for myocardial perfusion scintigraphy (MPS). It is also a tumor seeking agent. Here, we present a case of 51 year old male who underwent Tc-99m MIBI myocardial perfusion study due to permanent chest pain after coronary angiography. Abnormal MIBI uptake in the thorax was detected in the raw images. This single finding led to further investigation and thoracotomy proved that the lesion was benign thymoma. Thymomas are often asymptomatic or have a non-specific presentation. They are often detected coincidentally on images performed for any other reasons. We wanted to emphasize that during of MPS, the raw data should always be reviewed as occasionally valuable additional information on noncardiac pathology could be recognized by extracardiac uptake, as in this case.Conflict of interest:None declared.

2116 Scintigraphic patterns of chemotherapy resistance: preliminary data of simultaneous scintigraphy with two tumor seeking agents: 67Ga and 99mTc-MIBI

2116 Scintigraphic patterns of chemotherapy resistance: preliminary data of simultaneous scintigraphy with two tumor seeking agents: 67Ga and 99mTc-MIBI

6-Deoxy-6-[&lt;sup&gt;131&lt;/sup&gt;I]iodo-&lt;small&gt;L&lt;/small&gt;-ascorbic Acid for the &lt;i&gt;in Vivo&lt;/i&gt; Study of Ascorbate: Autoradiography, Biodistribution in Normal and Hypolipidemic Rats, and in Tumor-Bearing Nude Mice

Normal female rat distribution studies showed high and specific uptake of 6-deoxy-6-[(131)I]iodo-L-ascorbic acid (6-(131)IAsA) into the adrenal glands, known to highly express the ascorbate sodium-dependent vitamin C transporter-2 (SVCT-2), and the adrenal gland was clearly visualized by whole-body autoradiography. Preinjection of sulfinpyrazone, a known blocker of ascorbate transport, with 6-(131)IAsA resulted in decreased uptake of radioactivity in rat adrenal glands compared to the control group, seemingly illustrating the participation of the SVCT transporter (probably the SVCT-2 subtype) in the uptake process in vivo. 4-Aminopyrazolo[3,4-d]pyrimidine-induced hypolipidemic rats showed a 1.7-fold increase in adrenal uptake of radioactivity at 30 min postinjection of 6-(131)IAsA, compared to the control, with increased adrenal-to-liver and adrenal-to-kidney ratios. To further characterize 6-(131)IAsA for its tumor uptake properties, biodistribution studies were also performed using male nude mice implanted with either Y-1 adrenocortical tumor cells or adrenal medulla-derived PC12 cells. None of these tumors exhibited relevant uptake of 6-(131)IAsA while normal adrenal glands showed high uptake of radioactivity, suggesting that these tumors in this model have only a poor transport capacity for this agent. The present study demonstrates that the use of radioiodinated 6-IAsA may help to obtain information about functional alterations in diseased adrenal glands, but it does not exhibit desirable properties as a tumor-seeking agent for ascorbic acid bioactivity.

Cis-4-[18F]-Fluoro-l-proline fails to detect peripheral tumors in humans

System A amino acid transport is increased in transformed and malignant cells. The amino acid 4-cis[(18)F]fluoro-l-proline (cis-[(18)F]FPro) has been shown to be a substrate of the System A amino acid carrier. In this pilot study, we investigated the diagnostic potential of cis-[(18)F]FPro in patients with various tumors in comparison with [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET). Eight patients (seven females, one male, age range 43-77 years) with large primary, recurrent or metastatic tumors of different histologies were included in this study. One patient had a recurrent non-Hodgkin lymphoma; two patients, metastatic colon or rectal cancer; one, a metastatic endometrial cancer; one, a multiple myeloma; one, an Ewing sarcoma; one, a metastatic breast cancer and one, a gastrointestinal stromal tumor. PET scans of the trunk were acquired at 1 h after intravenous injection of 400 MBq cis-[(18)F]FPro and compared to PET scans with [(18)F]FDG. None of the tumors or metastatic lesions in this series of patients demonstrated relevant uptake of cis-[(18)F]FPro. In contrast, all tumors with exception of the multiple myeloma showed an intensive uptake of [(18)F]FDG. The mean standardized uptake value of cis-[(18)F]FPro in the tumor or metastases was significantly lower than that of [(18)F]FDG uptake (1.7+/-0.6 vs. 5.7+/-3.0; n=8; P<.01). Although other System A-specific tracers have shown relevant tumor uptake, cis-[(18)F]FPro fails to detect most types of human tumors. Based on these results, we cannot recommend a further evaluation of this tracer as a tumor-seeking agent.

Role of99mTc-(V)DMSA in Detecting Tumor Cell Proliferation

Pentavalent technetium-99m dimercaptosuccinic acid (99mTc-(V)DMSA) is a tumor-seeking agent which was introduced to evaluate, image, and manage many types of cancers. In this review, the beginning of, and the most recent applications of using this agent was appraised. The relation with tumor cell detection and proliferation was reported and several mechanisms of uptake of99mTc-(V)DMSA in tumor cells are described.

Role of 18F-FDG PET and PET/CT imaging in thyroid cancer

The commonly used procedure for the diagnosis of thyroid nodule malignancy is based on high resolution thyroid ultrasonography (US) combined with US-guided fine needle aspiration cytology (FNAC). The other imaging procedures have a limited role in malignancy diagnosis. However, nuclear medicine procedures, particularly scintigraphy with tumor-seeking agents such as 201-thallium (201-Tl), 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) and 99mTc-tetrofosmin may play an important role in the differential diagnosis between benign and malignant thyroid nodules in cases of non-diagnostic or inadequate FNAC. This type of scintigraphy can also be used in the follow-up of patients with cytologically ‘high’-risk thyroid nodules such as Hurtle cell adenomas and follicular adenomas. Furthermore, scans with tumor-seeking agents can be helpful in determining the preoperative staging of thyroid carcinoma patients with locally advanced disease, and in accurately evaluating the extent, and consequently, the surgical management of the disease.

99mTc-labeled 1-thio- β- d-glucose as a new tumor-seeking agent: Synthesis and tumor cell uptake assay

99mTc-labeled 1-thio- β- d-glucose ( 99mTc-1-TG) was synthesized under different ligand concentrations. 1-Thio- β- d-glucose (1-TG) showed different chemical properties and higher stability at acid pH as compared to neutral and basic pH. Under different ligand concentrations, 99mTc-1-TG was obtained with high labeling efficiency of >97%, but the HPLC chromatogram varied with the ligand concentration. The results of a tumor cell uptake assay also depended on the ligand concentration. With the lowest ligand concentration tested (0.5 mg/ml of 1-TG), we obtained the highest uptake. With different glucose and insulin concentrations, 99mTc-1-TG uptake was not significantly different from that of [ 18F]FDG.

In vivo absorption spectroscopy of tumor sensitizers with femtosecond white light

A system based on a femtosecond white-light continuum and a streak camera was used for recordings of the in vivo absorption spectra of the tumor-seeking agent disulphonated aluminum phthalocyanine. Measurements for different drug doses were performed on tumor tissue (muscle-implanted adenocarcinoma) and normal muscle tissue in rats. It was found that the shape of the spectrum is tissue dependent. The peak of the absorption spectrum is blueshifted in tumor tissue as compared with the muscle. Thus the contrast in the drug-related absorption can be altered by up to a factor of 2 from the primary drug molecular-concentration contrast between normal muscle and tumor by the proper selection of the illumination wavelength.

Paper Chromatographic and Paper Elettrophoretic Study of the Solution Chemistry of Tc—99m—Methylendiphosphonate and of Tc—99m—Dimercaptosuccinate for Improving the Tumouraffinity of Tc—99—m During Scintigraphic Imaging of Cancer

In order to find the conditions under which Tc-99m-methylenediphosphonate (Tc-99m-MDP) and Tc-99m(V)-dimercaptosuccinate (Tc-99m(V)-DMSA) may become tumour-seeking agents, leaving healthy organs free from the radionuclide uptake, the solution chemistry of these radiopharmaceuticals was studied by paper chromatography and paper electrophoresis in distilled water, in physiological saline, in NAHCO3, and ascorbic acid solutions. Both radiopharmaceuticals are anionic in the radiopharmaceutical solution but get easily hydrolysed to form cationic Tc-99m species which concentrates in healthy bone and in some bone metastases. Tc-99m (V)-DMSA being more stable remains long in the blood pool giving undesirable presence of the radionuclide in lung, heart and kidneys, in addition to its reduced uptake in bone metastases and in some primaries. We are trying to eliminate these drawbacks of healthy organ uptake of Tc-99-m(V)-DMSA not only to get a clean scintigraphic image of the tumour with this radiopharmaceutical but to extend its formulation, thus obtained, to prepare radiopharmaceutical with Re-188, which is the higher homologue of Tc-99m, for systemic therapy of cancer. Essentially similar solution chemistry of both radiopharmaceuticals suggests that like Tc-99m-MDP, technetium-99m-dimercaptosuccinate is also a complex of tetravalent Tc-99m and not of pentavalent Tc-99m as so far supposed to be.