Abstract

IJNM

Indian Journal of Nuclear Medicine

0972-3919

Society of Nuclear Medicine, India

ijnm-19-4-session-003

Session III

122004

194133139

Synthesis of Isoniazid Based (INDISCAN): Potential Infection Imaging Agent Using NM and MR Techniques

Mishra

Anil Kumar

Tiwari

Anjani Kumar

Sharma

Rajnish

Chuttani

Krishna

Mishra

Pushpa

Kumar

Nitin

Rawat

Harish

Sharma

Rakesh Kumar

Mondal

Anupam

Kashyap

Ravi

Ravindranath

Institute of Nuclear Medicine and Allied Sciences, Brig. SK Mazumdar Road, Delhi-54

Ref. No: 16AKRPH7

AbstractObjective

Isoniazid (INH) is the main treatment drug in the multidrug therapy of Tb since its introduction in the 1950s. The recent cloning of catalase gene (KatG) and the INH resistance determinant (InhA) have unveiled the mystery of INH. Cloning and expression of InhA gene revealed for the first time that INH interferes with mycotic synthesis. Recent developments in immunology and particularly in Leishmaniasis have led to the understanding of T helper (h) types in the pathogenesis of intramacrophage infection.

Our main objective of the present invention is to introduce a PDL group without compromising its biological activity for early diagnosis of infection using neuclear medicine and MR techniques.

Methods

The isonicotinic acid hydrazide was conjugated to polydentate ligand (PDL) viapeptide linkage. The Overall yield of three steps synthesis starting from PDL is above 80%. The new ligand binds with infection site through specific interaction with gene iniA, iniB and iniC under pathological conditions. In particular, complexation of PDL moiety with ^99mTc and Gd^+III showed excellent results as metallopharmaceutical for medical imaging.

For the first time a polydentate chelating agent is being conjugated with antibiotic to label with radionuclides and paramagnetic metal ions to discriminate the non-specific or undefined coordination chemistry which is a big question in the case ciprofloxacin and other antibiotics (which are the atoms participating in coordination?).

The INH-PDL was characterized by Mass spectroscopy in ESI positive mode,M+H⁺ was found to be 632.2.The complex was successfully labeled with ^99mTc radionuclide with more than 95% labeling efficiency with defined radiochemistry. Radiolabeled INH-PDL was stable more than 24h under physiological conditions. Blood kinetics showed rapid first rapid clearance with biological half life t_1/2 (F) = 11 min.

Results

Imaging of a normal rabbit and a rabbit with induced tuberculosis was carried out. An appreciable activity was visualized in liver and kidneys. In experimental rabbit similar pattern was observed with the accumulation of activity at the tubercular site at 24 h post injection.

Biodistribution revealed major accumulation in liver 6.30 ± 0.58%ID/gat 1 hand 6.25 ±0.11 at 4h and in kidneys 7.65 ± 0.52%ID/g at 1h and 6.70 ± 0.28% ID/g at 4h. Radiotracer uptake was also seen in bone 1.32 ± 0.180% ID/g at 1h.

Conclusions

From the present work it can be concluded that the radiolabeled INH-PDL accumulate at the site of infection.

Studying Pharmacodynamics Using Nuclear Medicine Techniques: Evaluation of Seabuckthorn

Kashyap

Ravi

¹Ganju

Lilly

²Chopra

M.K.

¹Padwad

Yogendra

²Singh

Richa

²Bhatnagar

Parul

¹Mishra

¹Institute of Nuclear Medicine & Allied Sciences (INMAS), Brig. S.K. Mazumdar Marg, Delhi-110054²Defence Institute of Physiology Allied Science (DIPAS), Brig. S.K. Mazumdar Marg, Delhi-110054

Ref. No: 17RKRPH9

AbstractObjectives

Nuclear medicine offers a unique opportunity to study the in vivo physiology of a subject. This ability can be effectively utilized to study the effects of any pharmaceutical under evaluation. The present paper describes the pertinent issues, which need to be considered to evolve a scintigraphic approach for evaluation of a drug preparation.

Methods

Immunomodulatory property of seabuckthorn was to be evaluated. An inflammatory model of adjuvant-induced arthritis in rats (seven groups of ten each) was created. Seabuckthorn was administered intra-peritoneally to treat the inflammation. Administration of seabuckthorn was done from day one, five days prior and ten days after the onset of inflammation. The extent of inflammation was studied on 1,7, 14,21 and 28^th day, using scintigraphy, clinical evaluation and by assessing lymphocyte proliferation. Standardisation of the scintigraphic technique was done for optimization of imaging time, processing method, and selection of radiopharmaceuticals.

Results

The results obtained by a non-invasive scintigraphic technique were similar to, as noted by, lymphocyte proliferation evaluation.

Conclusions

The observation suggests that seabuckthorn extract has a significant anti-inflammatory activity, which should be further evaluated for it to be used as an alternative approach for the treatment of arthritis.

Key wordsPharmacodynamicsDrug DevelopmentScintigraphy

Preparation, Characterization & Bio-Evaluation of ^99mTcN-Colchicine Dithiocarbamate

Korde

Aruna

Mallia

Madhava

Mathur

Anupam

Sarma

H.D.

Banerjee

Sharmila

Venkatesh

Meera

Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085

Ref. No: 18AK1RPH9

AbstractObjective

Resistance to chemotherapeutic drugs is a major limitation to treatment of cancer. In-vivo imaging of Multi drug resistance (MDR) is still a challenge. Colchicine a tricyclic alkaloid from Colchicum autumnale, is known to possess cyto-toxic activity and ¹1C labeled Colchicine is being evaluated elsewhere in the world for imaging MDR. Objective of the work is to radiolabel colchicine with ^99mTc using ^99mTcN core.

Methods

To facilitate radiolabeling with ^99mTc, amino derivative of colchicine was synthesized by the acid hydrolysis of colchicines and characterized by 1H-NMR spectroscopy. This was further used for preparing colchicine dithiocarbamate by reacting with 1.1 eq of carbon disulphide in presence of crushed sodium hydroxide in dry diethyl ether. The [^99mTcN]²⁺ core was prepared from freshly eluted sodium pertechnetate using the kit from Cis Bio International, France. Labeling with dithiocarbamate was achieved by mixing 0.5 ml of [^99mTcN]²⁺ core to 0.5 ml of ligand solution in saline and incubating for half an hour at ambient temperature. The complex was characterized by TLC and paper electrophoresis. In-vitro evaluation of the labeled product was carried out in three types of tumour cells namely fibrosarcoma, melanoma and lymphoma. In-vivo biodistribution studies were carried out in fibrosarcoma tumour bearing mice. 15 min, 1 hr and 4hr post injection studies were carried out to determine the percentage uptake of injected dose in tumor and all major organs.

Results

Yield of amino colchicine derivative was 70% and that of dithiocarbamate colchicine was found to be 80%. Ra-diochemical complexation yield of ^99mTcN-colchicine dithiocarbamate was > 95%. Reasonably significant (54.8,57.1 and 66.2%) cellular uptake was observed with fibrosarcoma, melanoma and lymphoma cells respectively after one-hour incubation at 37°C. On the contrary, ^99mTc-Nitrido core showed negligible uptake in these tumour cells. In-vivo biodistribution showed major accumulation of the injected activity (61.7%) in liver within 15 min. Lungs and spleen showed 13.5 and 2.68% of the injected dose. 0.42(0.24)% of injected dose was seen per gm of tumour tissue at 1h. p.i. T/B and T/M ratio increased from 0.52 to 2.4 and 0.68 to 1.16 from 15 min. to 4 hr. respectively.

Conclusions

Colchicine could be successfully labeled with the ^99mTCN core in high specific activity. In-vitro studies indicate retention of colchicine activity in tumor cells after modification at seventh position. However lipophilicity of the complex limits its application for in-vivo imaging and needs to be addressed.

Key wordsColchicine^99mTcN coreTumor

5I-DOTA-TATE, Somatostatin Receptor Imaging

Korde

Aruna

Pandey

Usha

Banerjee

Sharmila

Sarma

H.D.

Mukherjee

Archana

Samuel

Grace

Venkatesh

Meera

Radiopharmaceuticals Division, BARC

Ref. No: 19AKRPH10

AbstractObjective

Somatostatin is a regulatory cell membrane receptor protein that is over expressed in many tumors. Radiolabelled somatostatin analogues are successfully applied for visualization of receptor-positive tumors. DOTA-TATE (1,4,7,10-tetraazacyclododecane tetracetic acid-Tyr³-Octreotate) is one such somatostatin analogue that is being currently pursued for use in somatostatin-based peptide receptor imaging (sst-PRI) and peptide receptor radiotherapy (sst-PRRT). The objective of the work was radiolabeling DOTA-TATE with ¹²⁵I and its pharmacokinetics evaluation.

Methods

DOTA-TATE was obtained as a gift from PiChem, Finland as a part of the co-ordinated research project of the IAEA, Vienna. Radioiodination of DOTA-TATE conjugate was carried out with ¹²⁵I using Chloramine-T as an oxidizing agent. The reaction was carried out at room temperature for 90 seconds after which it was quenched with 500 mL of 0.05 M phosphate buffer. Paper electrophoresis was used to determine the radiochemical yield. Purification of the labeled conjugate was effected on C18 Sep pak cartridge. Characterisation of ¹²⁵I-DOTA-TATE was carried out by paper electrophoresis and HPLC with C18 reverse phase column and gradient elution technique (Water: Acetonitrile with 0.1% trifluoroacetic acid). ¹²⁵I-DOTA-TATE stored in buffer as well as in serum was studied for stability. Biodistribution studies were carried out in normal Swiss mice by injecting 37 kBq/animal. Animals were sacrificed at 3 h, 24 h and 48 h post injection.

Results

At 1:20 molar ratio of iodine: peptide, ~90% radioiodination yield was observed with >95% radiochemical purity. ¹²⁵I-DOTA-TATE (Rt=15 min) was well separated from ¹²⁵I^- in HPLC, indicating the efficacy of C-18 sep-pak column in the purification. ¹²⁵I-DOTA-TATE was found to be stable both in phosphate buffer and serum when stored overnight at ambient temperature with negligible serum protein binding. Pharmacokinetics pattern was encouraging showing rapid blood clearance with no retention in vital organs such as liver, intestine, heart, lungs etc. Low thyroid uptake was indicative of the in vivo stability of the product.

Conclusions

Radioiodinated DOTA-TATE holds promise for imaging (using ¹²³I) and therapy (using ¹³¹I) of somatostatin expressing tumors.

Key words¹²⁵I-DOTA-TATESomatostatin receptor imaging

Preparation of ¹⁷⁷Lu-DOTA-TATE: A Somatostatin Receptor Specific Therapeutic Agent

Chakraborty

Sudipta

Das

Tapas

Banerjee

Sharmila

Samuel

Grace

Sarma

H.D.

Venkatesh

Meera

Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai-400 085

Ref. No: 20SCRPH11

AbstractObjective

Several peptide receptor-specific somatostatin (SST) analogs have been extensively investigated for in-vivo application in peptide receptor radionuclide therapy (PRRT). These studies exploit the over-expression of SST receptors in tumor cells compared to normal tissues. Somatostatin analogues such as, DOTA-Tyr3 -Octreotate (DOTA-TATE) labeled with⁹⁰ Y have been developed and have shown promising results. However, the unavailability of the commercial ⁹⁰Sr-⁹⁰Y generator is one of the major drawbacks towards the use of ⁹⁰Y. Moreover, the longer tissue penetration range of⁹⁰ Y increases the radiation burden to the normal tissues, especially in case of smaller tumors. Hence, it is pertinent to radiolabel DOTA-TATE with a radionuclide having more suitable nuclear decay characteristics. Recently, ¹⁷⁷Lu is being considered as another viable alternative for the development of new agents for PRRT. ¹⁷⁷Lu decays by emission of b^- particles with E_ of 497 keV to stable ¹⁷⁷Hf. It also emits g photons of 113 keV (6.4%) and 208 keV (11%) suitable for imaging studies. The comparatively longer half-life of ¹⁷⁷Lu (6.71 d) provides logistics advantages and the high thermal neutron capture cross-section of ¹⁷⁶Lu (2100 b) makes it quite convenient to produce high specific activity ¹⁷⁷Lu using moderate flux reactors. In the present paper, the preparation of ¹⁷⁷Lu labeled DOTA-TATE is described.

Methods

¹⁷⁷Lu was produced by thermal neutron irradiation enriched Lu₂O₃ target (60.6% ¹⁷⁶Lu) in Dhruva reactor at a flux of ~3^´10¹³ n/cm²/s for 7 days. The ¹⁷⁷Lu labeling of DOTA-TATE was effected by adding 20 mL ¹⁷⁷LuCl₃ (1.13 nmol Lu) solution to a 200 mL solution of the conjugate (17.41 nmol) in 0.1M ammonium acetate buffer of pH 5. The reaction mixture was incubated at 50°C for 1 h. The radiolabeled conjugate was characterized by PC in 50% aqueous acetonitrile as well as by HPLC using acetonitrile and water (with 0.1% TFA) as the mobile phase applying gradient elution technique. Various reaction parameters were varied extensively in order to optimize the complexation yield. Preliminary biodistribution studies of the radiolabeled conjugate were carried out in normal Swiss mice.

Results

¹⁷⁷Lu was produced with a moderately high specific activity of ~100-110 TBq/g (~3^´10³ Ci/g) with excellent radionuclidic purity (~100%). In PC, using 50% aqueous acetonitrile it was observed that ¹⁷⁷Lu-DOTA-TATE moved towards the solvent front (R_f = 0-7-0.9), while the uncomplexed ¹⁷⁷Lu remained at the point of spotting (R_f = 0). ¹⁷⁷Lu-DOTA-TATE complex was obtained with high radiochemical purity of ~98% under optimized reaction conditions. The radiolabeled conjugate was observed to be stable at room temperature for 7 days. Results of the biodistribution studies carried out in normal Swiss mice revealed that the complex exhibit excellent renal clearance with no uptake in any specific organ.

Conclusions

The radiolabeling procedure of DOTA-TATE with ¹⁷⁷Lu was optimized to obtain the radiolabeled conjugate in high radiochemical purity. Preliminary bio-distribution studies showed no retention of activity in any major organ. However, to determine the receptor specificity of the radiolabeled conjugate detailed biological studies are absolutely necessary and are presently being pursued.

Key wordsSomatostatin receptors¹⁷⁷LuDOTA-TATEradionuclide therapyPRRT.

Preparation and Preliminary Biological Evaluation of a ¹⁰⁹Pd Labeled Water Soluble Porphyrin

Chakraboty

Sudipta

Das

Tapas

Banerjee

Sharmila

Sarma

H.D.

Venkatesh

Meera

Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Trombay, Mumbai -400 085

Ref. No: 21SCRPH12

AbstractObjective

It is well documented that porphyrins have the tendency to accumulate in tumor cells. Therefore porphyrin derivatives radiolabeled with suitable therapeutic radionuclide could be envisaged as potential agents for targeted tumor radiotherapy. Working in this direction, we have synthesized a water soluble porphyrin derivative viz. meso-5,10,15,20-tetrakis [3-bis (carboxymethyleneoxy)-phenyl] porphyrin and radiolabeled it with ¹⁰⁹Pd. ¹⁰⁹Pd could be considered as a useful therapeutic radionuclide owing to its suitable nuclear decay characteristics. ¹⁰⁹Pd decays by emission of b^- particles [Eb_(max)= 1.06 MeV] with a half-life of 13.5 h to stable ¹⁰⁹Ag. It also emits low energy low abundance g photons of 88 keV (3.7%) suitable for simultaneous scintigraphy.

Methods

¹⁰⁹Pd was produced by irradiation of anhydrous PdCl₂ powder in CIRUS reactor at a flux of ~2^´10¹³ n/cm²/s for 3 days. The irradiated powder was dissolved in DMSO by gentle warming, resulting in the formation of ¹⁰⁹Pd (DMSO)₂Cl₂, which was subsequently used for radiolabeling. The porphyrin derivative was synthesized by refluxing an equimolar mixture of 3,4-dicarboethyoxymethyleneoxy benzaldehyde and pyrrole in a mixture of propionic acid and nitrobenzene for 1 h followed by hydrolysis with KOH in THF at room temperature. The crude product was purified by column chromatography using water as the eluting solvent. The purified product was characterized by elemental analysis as well as by spectroscopic techniques such as, UV-VIS, FT-IR and ¹H-NMR spectroscopy. The radiolabeling of the porphyrin derivative was achieved by adding ¹⁰⁹Pd(DMSO)₂Cl₂ solution to 4 mg of porphyrin derivative dissolved in 0.1M ammonium acetate buffer (pH~5) and incubating the resulting mixture at 80°C for 15 min after adjusting its pH to ~8. The complex was characterized by paper chromatography (PC) using 25% aqueous acetonitrile and by UV-VIS spectroscopy. Several reaction parameters were varied extensively in order to achieve the optimum protocol for radiolabeling. To determine the tumor specificity of the radiolabeled porphyrin preliminary biodistribution studies were carried out in Swiss mice bearing fibrosarcoma tumors.

Results

In PC using 25% aqueous acetonitrile, it was observed that, the ¹⁰⁹Pd-porphyrin complex moved towards the solvent front (R_f =0.8-1) while uncomplexed ¹⁰⁹Pd did not move from the point of application (R_f =0). A maximum complexation yield of ~97% was achieved under optimized conditions. The complex was observed to be stable upto 24 h at room temperature. Results of the biodistribution studies revealed good tumor uptake [(2.80±0.57)%/g] within 30 min post-injection and it remained almost constant till 24 h. Though initially the uptake in blood, liver, intestine and muscles were high, it decreased with progress of time. At 3 h post-injection the tumor/blood and tumor/muscle ratios were found to be 1.07 and 1.52, respectively which increased to 4.36 and 38.0 at 24 h post-injection. The complex showed predominately renal clearance [(50.37±7.48)% at 30 min post-injection].

Conclusions

Present studies showed that the ¹⁰⁹Pd labeled porphyrin prepared exhibited encouraging results and warrants further investigations.

Key words¹⁰⁹PdPorphyrinTargeted radiotherapy

Utility of ^99mTc-MDP Bone SPECT in Chronic Low Backache

Prasad

Vikas

Parmar

Madan

Bhattacharya

Anish

Singh

Baljinder

Mittal

B.R.

Deptt. of Nuclear Medicine, PGIMER, Chandigarh - 160 012

Ref. No: 22VPSKJ8

AbstractIntroduction

Low backache has become a very common problem and management depends upon proper diagnosis of the etiology. Bone SPECT has been proved to be a useful modality in these patients to rule out the bony abnormality as the cause of the pain. This study was carried out to determine the role of MDP bone SPECT vis-à-vis MRI in the management of low backache.

Material and Methods

Thirty five patients (26 M, 9 F) in the age group 20-75 years (mean 43.33 ± 14.18) with history of chronic low backache of more than one year duration were subjected to ^99mTc-MDP Bone SPECT of the lumbosacral spine. The results of the bone SPECT were compared with the MRI findings.

Results

Of the 35 patients, 29 had PIVD, 14 nerve root compression, 7 lumbar canal stenosis (LCS) and 2 patients had facet arthropathy on MRI. Bone SPECT showed no abnormal osteoblastic activity in 19 patients, and thus these were stratified into the group of patients requiring either subarachnoid steroid injection to alleviate symptoms due to inflammation or decompression surgery for PIVD. Eight of the 14 patients with nerve root compression did not show any abnormal osteoblastic activity. The abnormal osteoblastic activity seen in 16 patients on bone SPECT was mainly located in the pedicles, facet and vertebral body. Three patients had facet arthropathy on bone SPECT and were placed into the group requiring intra facet steroidal injection. Seven patients had abnormal osteoblastic activity in the pedicles suggesting fracture which was managed accordingly.

Conclusions

Our findings suggest that bone SPECT is complimentary investigation to MRI that may be used to stratify patients into probable group of responders and non-respond-ers to treatment modalities like intrafacetal or subarachnoid steroid injection or decompression surgery.

Key words^99mTc-MDP Bone SPECTLow backache

A Comparative study of Serum PSA and Bone Scintigraphy in Detecting Skeletal Metastasis in Patients with Carcinoma Prostate

Prasad

Vikas

Mittal

B.R.

Bhattacharya

Anish

Singh

Baljinder

Mandal

A.K.

Deptt. of Nuclear Medicine & Urology, PGIMER, Chandigarh -160 012

Ref. No: 23VPSKJ11

Abstract

Serum Prostate Specific Antigen (PSA) is considered as one of the most accurate markers for monitoring the progression of carcinoma prostate. However, radionuclide bone scintigraphy is also a very sensitive non-invasive method for identifying skeletal metastasis in these patients.

Aim

This study was carried out to evaluate the role of serum PSA in predicting bone metastasis as compared to the Tc99m MDP bone scan.

Materials and Methods

In this retrospective analysis of 59 patients in the age group of 49 to 80 years (mean ± SD 68.89 ± 7.69) who underwent 99mTc MDP whole body bone scan and simultaneous serum PSA levels were included. The patients were stratified into three groups according to the serum PSA level: Group A- PSA less than 10 ng/ml, Group B-PSA 10-20 ng/ml and Group C- PSA > 20 ng/ml. The serum PSA level of 10 ng/ml was taken as the cutoff value for predicting bone metastasis.

Results

Three of the 23 patients in group A and 5/6 patients from group B were positive for bony metastases on scintigraphy. Amongst the group C patients, 19/30 were detected to have bone metastases. The sensitivity and specificity of PSA for detecting bone metastasis was found to be 75% and 39% respectively with respect to bone scintigraphy. The positive predictive value, negative predictive value and overall accuracy of serum PSA was found to be 89%, 71.43% and 62.5% respectively.

Conclusions

This study underscores the need for the follow-up of patients with bone scan irrespective of serum PSA level.

Key wordsSerum Prostate Specific Antigen (PSA)Radionuclide Bone Scintigraphy

Combination of Bone, ^99mTc-HMPAO Leukocyte and Marrow Scan in the Evaluation of Diabetic Foot Complication.

Nath

S.D. Satish

Shihab-Al-Mohannadi

Agala-Al-Mutairi

Hayati

Hussain

Nuclear Medicine Dept, Organ Transplant Centre, Ibn Sina Hospital, Kuwait

Ref. No: 24 SN SK J12

AbstractObjectives

Diagnosis of osteomyelitis in diabetic foot is crucial as this condition is the most common cause of non traumatic lower extremity amputation. We need an imaging modality to differentiate between bone infection and soft tissue infection as diabetic foot ulcers are frequently associated with pedal osteomyelitis.

Materials and Methods

Ten adult diabetic patients with clinical suspicion of foot or ankle infection were prospectively evaluated using radiography, ^99mTcMDP bone scanning, leukocyte scanning, and marrow scanning to determine the presence of clinically suspected osteomyelitis. Mean age of patients was 62.24 (SD +/- 9.10). There were 6 males and 4 females patients. All the patients were diabetic had undergone renal transplant and were being followed up in our hospital.

Results

We had 4 patients in whom the bone and marrow scan was positive with leucocytes scan being negative. These finding are seen in diabetic osteoarthropathy, the incidence of infection being a remote possibility. Sensitivity and specificity to diagnose infection increases if the bone and leucocytes scan are positive with a negative marrow scan. These scan findings were seen in 3 of our patients who were later confirmed to be osteomyelitis on biopsy. The third group consisted of 3 patients who had increased radiotracer uptake in all the three scans. Osteomyelitis was diagnosed in only 2 patients. In our group the sensitivity and specificity was 87% and 92% respectively for all the three scans in combination to detect osteomyelitis.

Conclusions

The combination of WBC, MDP and Marrow Scan is a very sensitive and specific method to detect osteomyelitis in patients with concomitant diabetic osteoarthropathy, post operative healing and overlying skin ulcer.

Key wordsOsteomyelitis^99mTcMDP Bone ScanningLeukocyte Scanning

Is There a Significant Role for ^99mTc-Labeled Bisphosphonates in Orthopaedic Management?

Kumar

^1,²Kumar

²Howman-Giles

²Little

D.G.

¹Department of Nuclear Medicine and Clinical Ultrasound, Westmead Hospital²Department of Nuclear Medicine and Clinical Ultrasound, The Children's Hospital at Westmead

*Orthopaedic Research Unit, Sydney, Australia.

Ref. No: 25VKSKJ14

AbstractObjectives

Although ^99mTc-labeled bisphosphonates have been extensively used for diagnostic purposes, there are no systematic studies reported in the literature on treating orthopaedic disorders. The objective of this study is to develop ^99mTc-labeled APD (Pamidronate) as a new tool and monitor its biodistribution by gamma imaging modality. This approach has not been reported elsewhere and has the potential to improve the quality of treatment currently available.

Methods

APD was labeled with ^99mTc-pertechnetate in the presence of SnCl₂ as the reducing agent. ^99mTc-APD was administered intravenously (IV) subcutaneously (SC) and by direct application (Local) on surgically exposed rat femur. The animals were imaged and then sacrificed at 2hr or 24hr post-injection. Various organs were harvested and their radioactivity was estimated to establish the biodistribution of ^99mTc-APD.

Results

Intravenous injection (IV).When^99mTc-APD was administered IV, it appeared instantly in the blood pool. The 2 hr and 24 hr images showed that the labeled compound accumulated predominantly in the skeletal structure. At 2 hr post-injection ^99mTc-APD accumulated in the right and left femurs at 2.2 ± 0.15% ID/g and 2.16 ± 0.15% ID/g respectively. There was no significant soft tissue uptake including the kidneys (0.24 ± 0.05% ID/g). At 24 hr post-injection the results showed significant increase in the activity associated with the femurs (2.42 ± 0.18% ID/g). The soft tissue activity was negligible with the exception of the kidneys (0.22 ± 0.03% ID/ g), which is consistent with the imaging studies. Subcutaneous injection (SC)When^99mTc-APD was injected SC, more than 70% of the injected dose was localised at the site of injection within 2 hr post-injection, which decreased dramatically down to 22% after 24 hr period. The results might suggest that the compound slowly diffused into the systemic circulation, which is consistent with the increase in the femoral uptake from 0.5%ID/g at 2 hr to 1.47%ID/g, at 24 hr period. The renal uptake was very low at 0.22 and 0.19% ID/g at 2 hr and 24 hr studies. Local Application In this modality, the right femur of the rat was surgically exposed and ^99mTc-APD (50-60MBq/0. 1ml) was applied on the exposed femur and the rat was imaged at different time intervals. This modality would be useful only when primary surgical intervention was contemplated. The gamma images showed that majority of the injected dose was localised at the site of application (right femur) leaving very little activity in the other organs. The cut up results showed that 5.15± 0.26%ID/g of the activity in the right femur at 2 hr, which increased significantly to 7.94±0.99% ID/g at 24 hr post-injection. Notably renal uptake was very low (0.05 ± 0.068%ID/g) in comparison to the first two modalities.

Conclusions

The results clearly indicate that Local application is the best method to deliver maximum dose of ^99mTc-APD to the bone for orthopaedic repair processes. Since nephrocalcinosis may be associated with IV administration of APD, the low renal load by this method may obviate the possible renal damage. Therefore ^99mTc-labeled APD has unique potential in orthopaedic surgery and bone repair processes.

Key words^99mTc-labeled bisphosphonates^99mTc-APDBone Repair Processes

A Comparative Study of Bone Scans Findings and Serum Levels of Tumor Marker CA-15.3 in Patients with Breast Carcinoma.

Tiwari

B. P.

¹Nair

¹Naik

Apurva P.

¹Radiation Medicine Centre (BARC), Tata Memorial Centre Annexe, Parel, Mumbai-400 012²Department of Biochemistry, Tata Memorial Centre, Parel, Mumbai-400 012

Ref. No: 26 BP SK J15

AbstractObjectives

Breast cancer is one of the most frequent malignancies in the world. Available staging procedures to detect breast cancer (BC) are bone scan (BS), chest X-ray (CXR), liver ultrasonography (LUS), computerized tomography (CT), and estimation of serum tumor markers like carbohydrate antigen (CA-15.3) and carcino embryonic antigen (CEA). These procedures are expensive and may not be required in all cases. Bone scan is a very sensitive method to detect osseous involvement at very early stage. Literature reveals many reports showing the value of tumor marker CA-15.3 in the prognosis of patients with BC. It has been reported that a serum level of CA-15.3 > 25 U/ml is highly predictive of negative bone scan. Some references show different values of CA-15.3 atwhichBS could be negative. In order to correlate the findings of bone scan and the levels of CA-15.3 in patients with BC a prospective study was undertaken.

Methods

Patients with confirmed BC referred to Radiation Medicine Center for bone scan from May-July, 04 were included. A blood sample was drawn in each case for tumor marker assay (CA-15.3) on the same day as bone scan. All patients were referred first time for bone scan. Total seventy patients with mean age 47.5 +/- 9.42 years were studied. Normal range for CA-15.3 was 0-28 Units/ml.

Results

The findings are given in the following table.

Range of CA-15.3	Bone scan findings (No. of patients)		Total No.

(U/ml)	Positive	Normal

0-28	8	47	55
29-50	1	2	3
51-100	2	1	3
101-500	3	2	5
>500	3	14
Total	17	53	70

As indicated in the table, 55 patients had normal Ca-15.3 and 15 patients had elevated value of CA-15.3. Eight (14.5%) of the 55 patients with normal CA-15.3 had abnormal bone scan. Fifteen patients had CA-15.3 levels above the normal range and among these, 9 (60%) had abnormal bone scan.

Conclusions

While prima facie it would appear that high levels of CA-15.3 correlate with abnormal bone scan, it is also true that the numbers are small at present and conclusions about the validity of CA-15.3 as marker of bone metastases may be premature.

Key wordsCarbohydrate Antigen (CA-15.3)Breast CancerCarcino Embryonic Antigen (CEA)

Quantitative Assessment of ^99mTc-MDP Whole Body Bone Scans-A New Approach

Sukumar

Benjamin R

Shankar

Mahadev D

Padmavathi

Babu

Rao L

Nuclear Medicine Department, Image Hospitals, Ameerpet, Hyderabad-500 073.

Ref. No: 27 SB SK J16

AbstractAim

To Quantitate the whole body bone uptake of the ^99mTc MDP at 3 h and to assess its usefulness in Metabolic Bone Disease.

Materials & Methods

Our study group included 50 consecutive male and female patients. Patients were injected i.v. with 15-20 mCi (240-555 MBq) of ^99mTc MDP and after ~5min. Anterior & Posterior Whole body sweeps were acquired at a speed of 50cm/min and another sweep between 2.5 to 3.0 h with similar set up were acquired using ECAM Siemens gamma camera. The Geometric mean of early whole body counts was assessed from Anterior and posterior whole body sweeps. And 3 h whole body Geometric mean was assessed after decay correction and subtracting the kidney, bladder, injection site and whole body soft tissue counts. Percentage uptake was calculated by dividing the 3 h Geometric WB mean counts by early Geometric mean WB counts. Also SIJ and L4/S and L4/ Soft tissue ratio was quantitated using 3 h scans.

Discussion

Quantification of the third phase of bone scan has been approached by several investigators recently, using bone-to-soft-tissue, bone-to-bone and lesion-to-bone ratios (5-11). The Osteomalacia, renal osteodystrophy and Paget's group were all significantly different from the control group (P<0.00 in all cases). The Paget's group was also significantly different from all other groups (P<0.005 for the osteomalacia group, P<0.001 for the rest) and the renal osteodystrophy was significantly different from all except the thyrotoxicosis, and osteomalacia groups (P<0.001). In the osteomalacia and renal osteodystrophy groups there was appreciable overlap of individual patient results and the control range. In the osteoporosis, primary hyperparathyroidism and acromegaly groups, virtually all results lay within the control range and these groups were indistinguishable from the control population. For primary hyperparathyroidism these results are in keeping with other workers.

Age Variation of normal B/ST ratio

When the various decades were compared the only statistically significant differences were between the 51 -60 y group and the 61-70 and 71-80y group (P<01 in each case).

Conclusions

It is concluded, therefore, that on the grounds of variability of individual results together with failure to distinguish clearly between disease patients and controls, attempts to quantitate skeletal uptake of Rpcs by measurement of a bone to soft tissue ratio are of limited value in clinical practice. To overcome the errors/loopholes in the quantitation of skeletal uptake of Rpc by measurement of bone to soft tissue ratio we have used the whole body sweep technique. Our preliminary results suggest a positive trend wherein we can differentiate the percentage uptake values between normal and MBD.

Key words^99mTc MDPOsteodystrophyOsteomalacia