Three main decay process
Alpha (very small particles)
Beta (particle for treatment)
Gamma for imaging – wider and can go through tissue

Decrease of blood flow with larger tumor weight
Perhaps one reason Chemo does not work on larger NETs

Crossfire effect of radiolabeled treatment –

Advantages of Targeted Radionuclide Therapy
closer to personalized therapy

Side Effects -
Stem cells of bone marrow is important – Evidence of bone marrow damage appears at 4-6 weeks
Kidney also needs to be protected

Epidemiology
NETs is an orphan disease
Increase in case – is it early diagnosis – more environmental ?

Receptor Binding – Peptide Analog attaches to the tumor cell - once the analog attaches it release the radionuclide in the cage directly to tumor cell damaging the nucleus

PRRT – what has been used – In-111 DTPA  - y90 – lu177
Y90 – Long path length – lots of Energy
LU-177 shorter path length – less energy
IN-111 shortest path length – least energy

Nephrotoxicity related to PRRT
Kidney, spleen and tumor get the highest in PRRT -
Must use amino acid to block radiation

Y90 Dota-Toc
CR 5% PR 18% SD 69%

Indium 111 Octrotide Therapy
500 miliCurrie
Can result in stable disease – (88% were stable)
93 patients treated – 67% carcinoid – 12% pnet
Stable 93%, Partial 2%
Most other studies were done with lower dose
Median survival – 22 -25 months
PNETs had a closer to 40 month median survival

LU-177 Dota-Tate
PD 18% -  SD,PR CR 82%
LU vs I111 more PR and CR with LU 177

LU177 – IND 78,256  Filed June 2007 – Approved August 2010 for Excel Diagnostic
Excel worked with Rotterdam –
25 Patients in a year – No acute renal toxicity –

Patient example – shows great uptake and reduction of liver mets

Predictors of response to PRRT in NET
Needs to respond to OSCAN
Needs good uptake
F-18 FDG PET – give prognostics – FDG uptake is bad prognosticator predictor

Comparing PRRT – More CR and PR with Y90 and LU177  vs Ind111– but good stability with all

Conclusion
PRRT is novel and new
Limited Side Effects (3%)
Improved quality of life
Longer to progression and life 3-6 years

What is available in US

IN111 Yes and covered by most insurance (but not Medicare yet)

LU177 Yes in trail but no insurance coverage till multi center trail – but when the multi center starts – 2012 and may have some challenges with study design – ie random with no crossover

Y90 – not in US

Problem with Data
No Random Data
Administered dosage is different
Uptake  is different

Future PRRT
Treat in earlier stage
Need more data on Max Tolerated dose
Combo Therapy – both with radio nuclide and with other chemo agents
Hepatic artery infusion
PRRT before and/or after surgery as neo-adjuvant