Lymphoscintigraphy

SLN (Sentinel Lymph Node)SLN (Sentinel Lymph Node)

And Breast (cancer)And Breast (cancer)

Flow – Primary Exam – defines the flow of the Flow – Primary Exam – defines the flow of the radiocolloid through the lymph chains which can radiocolloid through the lymph chains which can reveal the following resultsreveal the following results

LymphedemaLymphedema ObstructionObstruction LeakLeakMapping – determines the followingMapping – determines the following Solid Epithelial TumorsSolid Epithelial Tumors SLNSLN Selective lymphad EnctomySelective lymphad Enctomy

Early Lymphatic Research

The following individuals were involved with The following individuals were involved with initial lymphatic researchinitial lymphatic research

1653 T. Bartholin1653 T. Bartholin 1685-1770 H.F. LeDran1685-1770 H.F. LeDran 1890 Halstead1890 Halstead

SLN - Breast

The SLN was defined in breast cancer by the The SLN was defined in breast cancer by the following individualsfollowing individuals

1907 Jaimseon and Dobson1907 Jaimseon and Dobson

1960 Gould – “Sentinal Node”1960 Gould – “Sentinal Node”

1977 Cabanas1977 Cabanas

1977 Norton1977 Norton

1977 Ege1977 Ege

Selective Lymphadenectomy

In the lymphatic system cancer spreads through the In the lymphatic system cancer spreads through the lymph chains and usually resides in what is known lymph chains and usually resides in what is known as the sentinel node. Removal of this node can as the sentinel node. Removal of this node can result in the following:result in the following:

Improved StagingImproved Staging Decreased Surgical MorbidityDecreased Surgical Morbidity Reduced Number Radical LN DissectionsReduced Number Radical LN Dissections

The Concept

Lymphatic spread of cancer is not only Lymphatic spread of cancer is not only orderly, but also predictableorderly, but also predictable

The histological status of the SLN is The histological status of the SLN is predictive of the status of the distant Lymph predictive of the status of the distant Lymph node basinnode basin

Skip metastases practically do not exist and Skip metastases practically do not exist and metastatic spread can be discovered via the metastatic spread can be discovered via the SLNSLN

The above diagram shows the SLN which containsThe cancerous cells. These cells then spread downThe lymphatic channels to other lymph nodes (second, Third tiers)

Patient Population

Early Breast Cancer will have the followingEarly Breast Cancer will have the following

Clinically Negative AxillaClinically Negative Axilla Tier 1 less than 2 cmTier 1 less than 2 cm 75% will be lymph node negative, beyond 75% will be lymph node negative, beyond

the SLNthe SLN

Adjuvant Therapy

Removal of the SLNRemoval of the SLN

Lymphatic Anatomy

Accompany blood supplyAccompany blood supply Ectoderm : mammary gland is organ of Ectoderm : mammary gland is organ of

skin - biologic unitskin - biologic unit Mammary lymph flow parallels lymph flow Mammary lymph flow parallels lymph flow

from skinfrom skin

Lymphatic Anatomy

Subcutaneous plexus : common drainage Subcutaneous plexus : common drainage location does not predict basin location does not predict basin

Important for injection siteImportant for injection site

Radipharmaceuticals

Visualize lymphatic channels from site of Visualize lymphatic channels from site of intestinal administration to first LN intestinal administration to first LN encounteredencountered

Biologic TrapBiologic Trap Active phagocytes by macrophagesActive phagocytes by macrophages

Left – Red dots idenfity radiocolloid migrating into the afferent lymph from an intersitial injection where they are trapped by the macrophagesWithin the sinusoid spaces.

Right – Magnification of a histoautoradiographh of the sentinel node Black dots show retention of the radioactive agent in the sinusoid spaces. Defines the ability to use radiocolloid to define the sentinel lymph node.

Radiopharmacenticals

Particle size Particle size Number of Particles (few)Number of Particles (few) Specific Activity (high)Specific Activity (high) Decrease heating timeDecrease heating time Too much clumping of the particles occurs Too much clumping of the particles occurs

after two hours of preparationafter two hours of preparation

Agent Concordant(nm)

Other(nm)

Median(nm)

99mTc-dextran 2-4   2

198Au-colloid 9-15 4-20/30 5-15

99mTc-antimonytrisulfide

3-12/30 15-25 17-22

99mTc-sulfur colloid (prefiltered)

5/15-50 5-25 <30

99mTc-HSA- 4-100   5-80

99mTc-sulfur colloid (unfiltered)

15/50-5000 100/200-1000

100-600

Approximate Ranges of Particles Size For Various RadiocolloidsEstimates

Particle size varies in the different agents used for this procedure.The next side discusses ideal particle size.

Ideal Drug

Radiocolloid between 100 – 200 nanometerRadiocolloid between 100 – 200 nanometer

This is not currently availableThis is not currently available

Radiocolloid not used is:Radiocolloid not used is:

Tc 99m DTPA – mannosyl – dextrinTc 99m DTPA – mannosyl – dextrin

Rapid clearanceRapid clearance

Low secondary LN accumulationLow secondary LN accumulation

Preferred Radiocolloid

Filtered Tc99m sulfur colloidFiltered Tc99m sulfur colloid Filter allows for particles that are < 30nmFilter allows for particles that are < 30nm If unfiltered colloid is used the particles will If unfiltered colloid is used the particles will

not travel as well through the systemnot travel as well through the system It is also suggested that the colloid be no It is also suggested that the colloid be no

more than 2 hours post preparationmore than 2 hours post preparation

Tc99m sulfur colloid

Not FDA approvedNot FDA approved

Filtered : 220 nanometerFiltered : 220 nanometer

50 –200 nanometer particle50 –200 nanometer particle

Not considered the ideal agent because of its Not considered the ideal agent because of its sizesize

Technique

Techniques that must be considered in this procedure Techniques that must be considered in this procedure are:are:

Site of the injection – most importantSite of the injection – most important

Volume – limited mLVolume – limited mL

Dose – to be discussedDose – to be discussed

Timing relative to surgery – after injecting the agent Timing relative to surgery – after injecting the agent and imaging the SLN the patient must be sent to and imaging the SLN the patient must be sent to surgery for removal of the radioactive nodesurgery for removal of the radioactive node

Site

Types of injection that could be done Types of injection that could be done Intratumeral : Not acceptableIntratumeral : Not acceptablePeritumeral : IM LNs (not acceptablePeritumeral : IM LNs (not acceptableIntradermal – Subremal : PreferredIntradermal – Subremal : Preferred The ideal injection is done just below skin The ideal injection is done just below skin

which is then picked up by the lymphatic which is then picked up by the lymphatic systemsystem

Injections are done around the tumor siteInjections are done around the tumor site

ROI 1 – Shows the injection siteROI 2 – Indicates the flow of the colloid through the lymphaticchannelROI 3 – indicates the sentinel Node

Graph displays the radiocolloid traveling through the lymphatic system over time.

This slide shows the difference between colloid size and itsability to flow through the infected system. Note that as thesize of the particle increases, the amount of nodes that “lightup” decrease. Hence, smaller colloid size is preferred when diagnosing disease.

Procedure0.2 ml – preferred volume0.2 ml – preferred volume0.5 mCi – dose 0.5 mCi – dose Injection is done just underneath the skin with numerous Injection is done just underneath the skin with numerous

injections around the tumor site, in a circular patterninjections around the tumor site, in a circular patternMassage breast – after injectionMassage breast – after injection9090° Arm Abduction – location of arm° Arm Abduction – location of armDynamic /Static – Dynamic process with static images Dynamic /Static – Dynamic process with static images

are acquiredare acquiredANT/LAO - imagesANT/LAO - imagesMark patient – mark the SLN when it is identifiedMark patient – mark the SLN when it is identified2 Hours – total time2 Hours – total time

Other Components

Vital Dye – can also be used along with the Vital Dye – can also be used along with the radiocolloidradiocolloid

Gamma probe – is used in the OR to Gamma probe – is used in the OR to determine which nodes are radioactive. determine which nodes are radioactive. Those that are are then removedThose that are are then removed

Success Rate

Fraction of patients in whom this procedure Fraction of patients in whom this procedure has been preformed identify 97 – 99% of has been preformed identify 97 – 99% of the SNLthe SNL

False Negative : 1 – 4%False Negative : 1 – 4%

Cases

These images illustrate variable patterns of lymphatic drainage. Imaging times occurred between 31 to 60 min post intradermal injection of 99mTc‑HSA nanocolloid •(A) RAO view shows single lymphatic vessel leading to single sentinel lymph node, with serial visualization of subsequent tier nodes •(B) LAO view shows 2 separate lymphatics leading through widely diverging pathways, to 2 separate but adjacent sentinel node and tier nodes•(C) LAO view shows 3 separate lymphatics leading, through widely diverging pathways•(D) RAO view shows multiple lymphatics leading from site of infection in outer upper quadrant to at least 3 separate sentinel nodes and subsequent tier nodes

This procedure done at UofL Hospital shows:•The injection site covered with a lead shield•Over time the lymph chain is noted•Sentinel node is defined

• The first image (L) shows the injection site that is located POST. Because of the excessive activity this injection site it can be seen in the ANT image. Note that slightly distal from the injection site the SNL.• Imaging is improved when (second image): A) the injection site is extracts; and B) A transmission image is take with the Co-57 flood. • In the last image (R) a transmission scan is done in the groin region to assure that there is no additional SNL.

Melanoma Upper Back

Posterior Projection

40 year old male presented 40 year old male presented with superficial spreading with superficial spreading malignant melanoma of the malignant melanoma of the left upper back.left upper back.

On dynamic images there is On dynamic images there is tracer uptake inferior and tracer uptake inferior and lateral to the melanoma site. lateral to the melanoma site. The intense focus is activity at The intense focus is activity at the injection sites around the the injection sites around the melanomamelanoma

Image on the left includes Image on the left includes activity from a transmission activity from a transmission source which helps to source which helps to outline the body.outline the body.

There are 3 discrete foci of There are 3 discrete foci of tracer uptake (shown by tracer uptake (shown by arrows) anterior, inferior arrows) anterior, inferior and lateral to the injection and lateral to the injection sites (shown by arrowhead). sites (shown by arrowhead).

Micrometatses were found Micrometatses were found in one of the marked lesions. in one of the marked lesions.

Melanoma Upper Back (Cont)

Anterior Projection

Static Images

Melanoma Left Cheek A lateral static image A lateral static image

from patient who had from patient who had a left cheek melanoma a left cheek melanoma (arrowhead shows (arrowhead shows sites of injection) sites of injection) demonstrates tracer demonstrates tracer uptake in the uptake in the submandibular and submandibular and posterior cervical posterior cervical lymph nodes (shown lymph nodes (shown by arrows). by arrows).

Pre-Operative Lymphatic Mapping Breast Cancer

Cancer was on the lower Cancer was on the lower side of the breast and was side of the breast and was injected with the injected with the radiocolloid (the dark black radiocolloid (the dark black area on the bottom of the area on the bottom of the breast). You can easily see breast). You can easily see that there are two that there are two lymphatics which leave the lymphatics which leave the breast (labeled with blue breast (labeled with blue LL) ) and go to two distinct and go to two distinct sentinel lymph nodes sentinel lymph nodes ((SLNSLN).).

Mapping The picture on the left The picture on the left

shows a sentinel lymph shows a sentinel lymph node (N) which is tinted node (N) which is tinted blue because it has taken blue because it has taken up the blue dye which was up the blue dye which was injected around the breast injected around the breast cancer. cancer.

The blue dye got there by The blue dye got there by traveling through the traveling through the lymphatics which leave the lymphatics which leave the breast and connect to the breast and connect to the SLN. This picture shows SLN. This picture shows the lymphatic vessel (L) the lymphatic vessel (L) with blue dye in it. with blue dye in it.

Breast Lymphoscintigraphy

Mapping of the breast is done in order to Mapping of the breast is done in order to surgically remove the SLNsurgically remove the SLN

This can be done with blue dye This can be done with blue dye This can be done with radiocolloid and a This can be done with radiocolloid and a

gamma knifegamma knife Usually both are done at the same timeUsually both are done at the same time

Other Applications

This procedure may also be useful with the following This procedure may also be useful with the following cancerscancers

Malignant melanomaMalignant melanoma Breast CABreast CA Cervical CA/Vulval CACervical CA/Vulval CA Colorectal CAColorectal CA Head and Neck CAHead and Neck CA Thyroid CAThyroid CA Gastrial/Esophageal CAGastrial/Esophageal CA Penile CAPenile CA