Early history of nuclear medicine in India

23 July 2009

The physicists have designed the “hot laboratory” in the institution following the specifications received from USA. They started radioisotope studies in 1951. The institution imported radioisotopes such as P-32, from Harwell, England. Incidentally, Dr Homi Bhabha organized this national conference at the suggestion of Pandit Jawaharlal Nehru who wanted that this opportunity may be used to review what has been done in the field of atomic energy till then. Over 100 specialists attended the meeting. The medical use of radioisotopes grew progressively with the commissioning of Apsara reactor in 1956. Besides diagnostic applications, the specialists started using radioisotopes such as iodine-131 and phosphorous-32 in radiotherapy. During early sixties, test monographs for a few radiopharmaceuticals appeared in international pharmacopoeia and in those of some countries. According to the reports available with the Radiopharmaceuticals Division, Bhabha Atomic Research Centre, the Drug Control Administration in India considered to clear radioisotopes under licence number 720. Uses of reactor- produced radioisotopes increased rapidly. They were in diverse form such as ready-to-use preparations for oral use and for use as injectables; short-lived radioisotope generators to prepare ready-to-use organ imaging agents by intravenous use; cold kits amenable to instantaneous and quantitative incorporation of short-lived radioisotopes for organ imaging etc.
-by Dr K S Parthasarathy
Early History of Nuclear Medicine in India

-by Dr K S Parthasarathy

It appears that the first reference on the medical use of radioisotopes in India has been by Dr Subodh Mitra former Director, Chitaranjan Hospital, Calcutta. In a paper titled “Health Protection, and Biological and Medical Applications of Atomic Energy” (Proceedings of the Conference on development of atomic energy for peaceful purposes in India, Nov 1954), he reviewed the radioisotope- related work in his institution.

The physicists have designed the “hot laboratory” in the institution following the specifications received from USA. They started radioisotope studies in 1951. The institution imported radioisotopes such as P-32, from Harwell, England.

Incidentally, Dr Homi Bhabha organized this national conference at the suggestion of Pandit

Jawaharlal Nehru who wanted that this opportunity may be used to review what has been done in the field of atomic energy till then. Over 100 specialists attended the meeting.

The medical use of radioisotopes grew progressively with the commissioning of Apsara reactor in 1956. Besides diagnostic applications, the specialists started using radioisotopes such as iodine-131 and phosphorous-32 in radiotherapy.

During early sixties, test monographs for a few radiopharmaceuticals appeared in international pharmacopoeia and in those of some countries.
According to the reports available with the Radiopharmaceuticals Division, Bhabha Atomic Research Centre, the Drug Control Administration in India considered to clear radioisotopes under licence number 720.

Uses of reactor- produced radioisotopes increased rapidly. They were in diverse form such as ready-to-use preparations for oral use and for use as injectables; short-lived radioisotope generators to prepare ready-to-use organ imaging agents by intravenous use; cold kits amenable to instantaneous and quantitative incorporation of short-lived radioisotopes for organ imaging etc.

The specialists in this field realized from the very beginning that the production, testing and supply of radiopharmaceuticals must fulfil medicolegal aspects related to the manufacture and use of conventional drugs and radiological safety requirements.

With regulatory control in mind, scientists in the Department of Atomic Energy established a radiopharmaceutical committee and a nuclear medicine committee.

These committees covered all aspects related to the safety of premises, products, patients, workers and the public. Director, BARC set up the Radiopharmaceutical Committee on February 23, 1968. The seven-member committee had Dr V.K.Iya then Head, Isotope Division and, a pioneer in the field as its convener.

The other members of the committee Dr R.S.Mani, Shri T.S.Murthy and Shri N.G.S.Gopal all from Isotope Division were eminently qualified specialists. Since radiopharmaceuticals have to satisfy the general requirements of conventional drugs, the committee had a representative from the Directorate General of Health Services (DGHS), Government of India, as a member.

The committee was to examine the production, practices, controls and the specifications of the radiopharmaceuticals supplied by the Isotope Division and also to consider and recommend the incorporation of radiopharmaceuticals into the Indian Pharmacopoeia.

Simultaneously, Director, BARC set up a five member Nuclear Medicine Committee with members drawn from BARC (Medical Division, Isotope Division, Radiation Medicine Centre), Directorate of Radiation Protection, and the Directorate General of Health Services, Ministry of Health, Government of India, Delhi.

The Committee evaluated the proposals for research, diagnostic and therapeutic uses of radioisotopes, approved a list of doctors trained in radioisotope techniques for established diagnostic and therapeutic procedures, developed procedures for giving standing clearances to established doctors for using standard products without delay and examined applications from every new user and for every new use of medical radioisotopes.

Another function of the nuclear medicine committee was to establish jointly with radiopharmaceutical committee procedures for the release of new products by the Isotope Division, BARC, for medical use.

These Committees were periodically reconstituted. When The Department of Atomic Energy set up the Board of Radiation and Isotope Technology (BRIT), the reconstituted Radiopharmaceutical Committee was brought under it. The Members of the Committee included specialists in nuclear medicine and pharmacy, Commissioner, FDA or his nominee and Drug Controller (India) or his nominee.

These committees met as frequently as necessary. These procedures assured overall though it may be difficult to find direct legal basis for their activities.

In 1977, the Director General of Health Services, Government of India notified that “radiopharmaceuticals” are exempt from the provisions of Chapter IV of the Drugs and Cosmetics Act 1940.

Many considerations must have contributed to this. The mass of radioactive material in any radiopharmaceutical is too trivial to cause any toxic effect; the normally used radioactive materials such as Tc-99m have very short half-lives; it may not be feasible to study them for sufficiently long periods to evaluate the relevant parameters as is done for conventional pharmaceuticals.

During the early sixties and seventies, BARC was the only agency preparing radio pharmaceuticals. In light of interactions with the specialists in BARC, the officials of the Directorate General of Health Services must have realized that granting exemptions will not have serious consequences. DGHS gave exemption nine years after the formation of the Radiopharmaceuticals Committee in which DGHS also had representation.

The Central Government set up the Atomic Energy Regulatory Board (AERB),to enforce safety provisions under the Atomic Energy Act 1962.

AERB reviewed the procedures followed for ensuring safety in the medical use of radioisotopes and retained the set up. In order to provide the much needed legal basis for carrying out medical radiation procedures safely, AERB issued Radiation Surveillance Procedures for Medical Applications of Radiation, 1989 exercising the powers vested under Rule 15 of the Radiation Protection Rules 1971.

As required in the Surveillance procedures, the Board issued several codes; one of them applied to nuclear medicine procedures.

With about 200 physicians licensed to practice nuclear medicine in the country, the facilities available are very modest. Just over 150 hospitals located mainly in cities provide the service.

The field is changing rapidly. The setting up of seven cyclotrons which serve several centres is a notable development.

India needs a ten-fold increase in facilities and man-power to ensure that its population derives the benefits from this advanced field of medicine.▄

Soybean plant adapts itself to Chernobyl

Recently, scientists have reported how soy plant adapted itself to the radioactively contaminated soil near the stricken Chernobyl nuclear power plant.
Dr.K.S.Parthasarathy


Date:23/07/2009 URL: http://www.thehindu.com/thehindu/seta/2009/07/23/stories/2009072350141300.htm Back Sci Tech



Soybean plant adapts itself to Chernobyl

The plants in the contaminated area have a mechanism to protect future progenies by blocking transfer of radio-nuclides to the seeds

Since April 1986, scientists got a unique opportunity to study the impact of radioactive contamination on the plants and animals living near Chernobyl.

The Chernobyl Forum, which is made up of eight specialized agencies of the UN, in its landmark report titled ‘Chernobyl’s Legacy: Health, Environmental and Socio-Economic Impacts,’ made some general remarks on the impact of the accident on the natural environment.
Details emerging

More detailed results of research are emerging now. Researchers from the Slovak Academy of Sciences reported that plants adapted very well to the contaminated environment (Journal of Proteome Research, 2009).

In 2007, they planted ordinary soybean seeds and flaxseeds at a contaminated field in the restricted area about 5 km from the stricken nuclear power plant and at a control field in the same region nearly 100 km away.

The soil in the contaminated area had 163 times more radioactivity (cesium-137) than that in the control area.

The seeds from the contaminated area had less length and width; they weighed about 50 per cent less than those from the control field. Their water-inhibition process was found to be different.

The uptake of radio-nuclides varied significantly within the plant and also between plants.

Though the plant absorbed about 10 per cent of the radioactive contamination, the seeds showed only very low levels of radioactivity. The plants have a mechanism to protect future progenies by blocking transfer of radio-nuclides to the seeds.

Brazil nut, which is well known as the most radioactive food, accumulates radioisotopes of radium. The root system of that tree covers a large area of soil and accumulates radioactivity from the soil.

Nature does not develop any mechanism to arrest the accumulation of radioactivity by the seed. “How do you explain the difference in behaviour between soy plant and Brazil nut tree?”

“I can only speculate that trees might have different mechanisms than plants. Trees are long-living organisms, when compared to crop plants, and thus might not have immediate interest to protect their future progenies from unfavourable environmental conditions”, Dr Martin Hajduch the lead author responded to my e-mail query.
Increased levels

The researchers wanted to develop a model for plant adaptation to increased levels of radiation. They froze the seeds with liquid nitrogen, crushed them to extract the mixture of proteins they contained and ran the seed proteins on 2-Dimensional gel Electrophoresis.

They looked for differences in expression levels of proteins between seeds grown in the contaminated field versus the control field.

The seeds from soy plants grown in contaminated field contained different types and amounts of proteins compared with those from control field. The former plants made many changes to defend themselves and adjusted the levels of several proteins that guard against heavy metals, disease etc.

The researchers found that a certain specific protein which, in test tube studies demonstrated a protective effect against radiation-induced damage, exhibited a 32 per cent higher expression in the seeds from contaminated fields.

The levels of hundreds of proteins which are known for their ability to shuffle other proteins around or tie them up in storage had been lowered.
Why soybean?

Why did they choose soybean plant for the study? “The reason is that soybean is a very important crop worldwide and I worked with it also before”, Dr Hajduch responded to my e-mail query.

“Large percentage of population depends on soybean”, he added.

Do you expect that the mechanisms you observed will be present in plants growing in high background radiation areas such as certain coastal regions in India?

“I would expect it as the mechanisms that plants use to protect their future progenies from harmful effects of radio-contaminated environment should be the same, regardless of the geographical location”, he replied.

Why should we carry out such studies?

“If scientists can understand how plants survive in ultra-hostile environments, it will help them engineer super hearty plants to withstand drought conditions or grow on marginal cropland”, (Aaron Rowe, wired.com, 2009).

K.S. PARTHASARATHY
FORMER SECRETARY, AERB

ksparth@yahoo.co.uk

© Copyright 2000 - 2009 The Hindu

Errors in radiation treatment of cancer

http://www.hinduonnet.com/thehindu/thscrip/print.pl?
file=2009071650111300.htm&date=2009/07/16/&prd=seta&


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Errors in radiation treatment of cancer
Several hospitals do not participate in the virtually free audit programme
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A well trained clinician can detect exposures involving a 10 per cent or more over-dosage
If the dose delivered is less than 5 per cent of the prescribed amount many cancer cells survive
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Everyone knows that Bhabha Atomic Research Centre (BARC) contributes to the strategic areas in the country. Unknown to many, BARC has been, since 1976, rendering a priceless service to radiation therapy centres in India. It ensured that the error in the radiation dose to millions of cancer patients who undergo treatment remained within the clinically acceptable limits of plus or minus 5 per cent of the dose prescribed by radiation oncologists.
Side effects
Doses more than 5 per cent of the prescribed amount, lead to side effects; if less than 5 per cent, many cancer cells survive, causing recurrence. A well trained clinician can detect accidental exposures involving a 10 per cent or more over-dosage, based upon an unusually high incidence of adverse patient reactions (ICRP, 2000).
BARC started a postal dose quality audit programme in 1976, with 9 hospitals, using cobalt-60 machines, participating.
Presently, the Radiation Standards Section (RSS), BARC sends capsules containing a specially prepared thermo-luminescent powder to the hospital. As per instruction, the medical physicist of the hospital exposes them to a specific dose under specified conditions before returning them to BARC. BARC scientists at Trombay estimate the dose accurately.
Most hospitals deliver accurate radiation doses to patients. Some hospitals default. Atomic Energy Regulatory Board (AERB)/BARC has asked hospitals showing unacceptable errors to stop treatment of patients till the issue is resolved.
The service covered over 250 hospitals in India. From the 1990s, 80 per cent of the participants show deviations within acceptable limits compared to 50 to 60 per cent during the earlier period.
Many years ago, in one hospital, the source in its cobalt unit did not move into the treatment position; the patients did not receive any dose for a month, till BARC scientists identified the defect.
Another instance
In another instance, the dose was down by 40 per cent, as an engineer who repaired the unit shortened the length of a cable pulling the source into position. The audit service identified the latter.
During 2007-2008, (48th and 49th batch audit) eight beams showed errors of serious magnitude, ranging from -13.2 per cent to 72.8 per cent. They were due to calculation errors or mistaken irradiation of capsules. A positive deviation leads to under-dosing and inadequate treatment.
We may not know of adverse effects, if any, on any patient, as no one reported them to AERB, though the Atomic Energy (Radiation Protection) Rules, 2004 demand it.
It is appalling to note that several hospitals do not participate in this virtually free service which provides an independent verification of the dose. During February 2006, BARC invited 100 hospitals to the audit programme. Only 33 joined. The number joined and the number of invitations sent for a few batches are as follows: March 2007 (63/142); September 2008(37/98); May 2009 (65/207).
Analysis completed
The analysis for May 2009 is being completed. The number of hospitals with deviations of more than 10 per cent for the other years were 1, 10 and 4. One may feel that the number showing greater deviations are very few.
Little comfort
That is of little comfort for the 40 to 50 patients who may receive improper or inadequate radiation treatment at the defaulting hospitals every day. If there is a -20 per cent deviation, all the patients will get overdosed. An alert oncologist may find something amiss.
The deviations in the institutions which do not cooperate are unknown.
The callous, inexcusable indifference shown by many hospitals in not participating in the audit is at the cost of the patients. Patients may suffer unexpected side effects or receive inadequate treatment due to correctable errors.
Patients getting treated with cobalt machines or accelerators, or their relatives, may ask the head of the radiation therapy department whether the hospital participates in the BARC dose audit programme.
A dilemma
The programme faces a dilemma. Being a routine service, BARC, a research and development agency, may find it difficult to continue the programme routinely.
The stakeholders such as AERB, BARC, Directorate General of Health Services, State Directorates of Medical Education and Health Services must hand over the responsibility of dose audit to an agency, accredited by AERB. BARC can monitor the functioning of this agency. Such an audit by independent agencies is essential to ensure that cancer patients are receiving the correct dose and to avoid gruesome consequences of over-exposures from radiotherapy equipment.
K.S. PARTHASARATHY
FORMER SECRETARY, AERB
( ksparth@yahoo.co.uk)
© Copyright 2000 - 2009 The Hindu

Nuclear medicine: a possible cure to blood cancer

The latest Image of nyuclear medicine showed that nuclear medicine procedures can be used to treat non-Hodgins lymphoma

K.S.Parthasarathy


July 3, 2009


Nuclear medicine: a possible cure to blood cancer
By Dr K. S Parthasarathy
Last month, Dr. A. Lagaru from the Division of Nuclear Medicine at Stanford University Medical Centre and his colleagues won the Society of Nuclear Medicine (SNM) 2009 Image of the Year award in Toronto.
Their poster paper contained an image clearly depicting how radio-immunotherapy can successfully treat non Hodgins Lymphoma (NHL), a potentially fatal form of blood cancer. The US National Cancer Institute estimates that in 2009, 65,980 new cases of NHL will be diagnosed in the US leading to 19,500 deaths.
“Radio-immunotherapy is a form of personalised medicine that combines the cancer fighting ability of radiation therapy with the precise targeting capacity of immunotherapy” (Imaging technology, June 16,2009). It is based on the body’s natural defence system, which protects it from many diseases.
The Stanford group studied two immunotherapy agents Bexxar, which is Iodine-131 based and Zevalin, which is Yttrium-90 based. Iodine-131 and Yttrium-90 are radioactive and emit particulate radiation. The immunotherapy agents home in on the cancerous cells, which become sitting targets for the particulate radiation emitted by Iodine-131 or Yttrium-90 as the case may be. The award-winning image is two sets of before and after Positron Emission Tomography scans of two patients, one treated with Bexxar and the other with Zevalin. Both patients did not show any metabolically active cancer as early as three months after treatment as demonstrated by their PET scans.
A PET scanner uses small amounts of certain radioactive drugs. A special camera that works with a computer provides pictures of the area of the body being imaged. Cancer cells grow and multiply uncontrollably. While doing so, they consume enormous amounts of energy. Basically, this energy comes from burning glucose
Cancer cell metabolise sugar at higher rates than normal cells. Fluoro deoxyglucose (FDG) is a marker for sugar metabolism. It contains Fluorine-18, a positron emitting radionuclide, whose presence will help to trace and locate the sites where FDG molecules get accumulated. Cancerous areas draw higher amounts of FDG, an ideal marker for the disease and its spread. PET scans produce three-dimensional images of the precise location of FDG in the body
“The image of the year was chosen because it shows how molecular therapy can cure non Hodgin’s lymphoma and it provides objective evidence that the patient has been cured”, Dr Henry N, Wagner Jr, a professor of environmental sciences at Johns Hopkins University and past president of the SNM clarified. The Stanford Specialists treated 71 patients. They showed that both the immunotherapy agents are safe and effective in treating non Hodgin’s lymphoma, even in cases where the disease has spread extensively. Twenty four out of 35 patients responded to Bexxar; 28 out of 36 to Zevalin. Taken the two groups together, 27 showed complete response to the drugs. However, in 19 patients the disease progressed in spite of treatment.

Radioactivity in phosphogypsum

The Atomic Energy Regulatory Board has issued a safety directive on the use of phophogypsum in building materials and agriculture. AERB reviewed the radiological safety significance of the material before issuing it. Phosphogypsum contains radioactive materials such as uranium-238 and radium-226.

K.S.Parthasarathy




July 2, 2009


Radioactivity of phosphogypsum to be studied

Phosphogypsum may contain radioactive materials such as uranium-238 and radium-226

The AERB has recently issued a safety directive on the use of phosphogypsum

If you visit any fertilizer factory, you may see large quantities of phosphogypsum (PG) in its premises. It is produced when rock phosphate is treated with sulphuric acid. Each ton of phosphoric acid leaves behind nearly five tons of PG. In many countries, the building industry extensively uses PG in producing cement, wallboard, and other building materials.

Phosphogypsum is not an innocuous material. Besides many heavy elements, it may contain significant quantities of radioactive materials such as uranium-238 and radium-226. Phosphogypsum produced from imported rock phosphates contains typically activity concentrations of U-238 in the range 0.1-0.2 Bq/g and Ra-226 in the range 0.5-1.3 Bq/g. (Bq is a unit of radioactivity. In a radioactive material having a radioactivity of one Bq, one atom disintegrates every sec).

The Atomic Energy Regulatory Board (AERB) has been examining the radiological safety implications of adding phosphogypsum in building and construction materials and in using it in agriculture.

Based on the principles followed internationally, the Board has recently issued a safety directive on the use of phosphogypsum.
Analysing content

The Board directed that all rock phosphate processing industries shall analyze Uranium-238 and Radium-226 content in each imported consignment of rock phosphate as well as in the phosphogypsum produced from its processing and shall report the results to AERB on a quarterly basis. AERB will review this data for a period of about two years for deciding on the frequency of such analysis in future.

AERB decided that its approval is not required for selling phosphogypsum for its use in building and construction materials, if the activity concentration of Ra-226 in it is less than or equal to 1 Bq/g.

If Ra-226 concentration in phosphogypsum is more than one Bq/g, the seller must mix it with other ingredients such that the Ra-226 activity concentration in bulk material is less than or equal to 1.0 Bq/g.

According to the International Atomic Energy Agency (IAEA), at one Bq/g, we need not regulate the material as the radiation doses to persons involved will be insignificant, irrespective of the quantity of material whether it is in its natural state or has been subjected to some form of processing.

AERB stated that its approval is not required for manufacturing and use of phosphogypsum panels or blocks, if they have Ra-226 activity less than 40 kBq/square metre area of any surface of the panels/blocks.

The possible annual increase in radiation dose to a person living in a building made with such panels is sufficiently low to qualify for exemption as per guidelines accepted by the European Commission on Radiation Protection.

The activity levels prescribed by AERB are such that they do not present an unreasonable radiation hazard to anyone.

Further, AERB decided that there need be no restriction for use of phosphogypsum in agricultural applications from the radiological safety considerations.

Twelve fertilizer plants in India presently process rock phosphates imported from countries such as Jordan, China, Morocco, Egypt, Senegal, Togo and others for production of phosphoric acid / fertilizers.
Annual generation

According to Building Materials and Technology Promotion Council, Indian companies generate 4.5 million tonnes of phosphogypsum annually. Over 10 million tonnes gets accumulated at plant sites. In Florida, U.S., alone, more than 900 million tons of PG is stacked in more than 25 stacks. Thirty million tons of PG is produced each year.

AERB received queries from the Ministry of Chemicals and Fertilizers, the Ministry of Agriculture and some of the fertilizer plants regarding restrictions based on radiological safety considerations, if any, on use of phosphogypsum in building and construction materials and in agriculture respectively.

As is the practice evolved by AERB from its inception, the Board issued the directive after a comprehensive and in-depth review of all aspects and after broad consultation with all stakeholders. The inputs needed to arrive at the directive came from extensive research by the scientists from the Bhabha Atomic Research Centre and from the deliberations of specialists in related fields.

K.S. PARTHASARATHY

(Raja Ramanna Fellow, Department of Atomic Energy)

ksparth@yahoo.co.uk

© Copyright 2000 - 2009 The Hindu