melanoma patients

By then, melanoma patients had been treated
with iodine-131-labelled monoclonal antibodies.
But as Paganelli points out, while an excellent idea,
this targetinghadlimitations–not least that the radiolabelled
antibodywent everywhere in the body. “The
idea Ihadwas to addapretargeting stage.We first target
the cancer cellswith a non-radioactive antibody,
which clears from the rest of the body. Then we
deliver a second, radiolabelled molecule that is
attracted by the antibody, and which is also cleared
rapidly fromthe body.” The aimis to deliver amore
effective dose to the target, while minimising sideeffects,
and has been a plank of Paganelli’s subsequent
researchandclinicalpractice; indeeditwas the
subject of a patent filed jointlywith the Italianministry
of research in 1991.
The sheer amount ofwork – that perspiration –-
and multidisciplinary understanding is a feature of
such research, says Paganelli. “Nuclearmedicine is
one of the few branches of medicine where you
have to be on top ofmaths, physics and chemistry as
well as the biology. If youwant to knowhowto apply
approaches such as pretargeting – the amount of
agents, the timing of doses, themolecular operation
and so on – you need to assemble a huge amount of
information.”Hismore than40-strongdepartment in
Milan – comprising physicists, chemists and technicians
aswell asmedicaldoctors–is testimony to the
need for amultidisciplinary approach.
Paganelli first went to work in general nuclear
medicine at the SanRafael hospital inMilan,with a
licence to continue his research, before being asked
byUmbertoVeronesi to setupa fledglingdepartment
at theEuropeanInstitute ofOncology in1994. Ithas
become the first and leading centre in Italy to carry
out therapeutic targeting work, and his closest col-

laborators arenowchemistMarcoChinol and physicistMartaCremonesi,
both based in his unit.
He had a window of opportunity at the start, as
therewere no regular patients for a fewmonths, and
he set about developing the pretargeting technique
with high-grade brain tumours, which have a very
poor outlook in the vastmajority of cases. “I started
withglioblastomabecause it is anorphandiseasewith
a suitable marker [the protein tenascin] and we
couldonlyhave a fewmonths to see if itworkedornot
– and if it did, it may then also work more easily in
cancers such as lymphoma. We used the avidin
biotinsystemandpublishedsome interesting results.”
His closest colleague on thiswork thenwasAntonio
Siccardi, professor of biology and genetics at the
University ofMilan.