This application concerns novel methods which enable or improve the ability of molecules, particularly large molecules, to cross the blood-brain barrier, the blood-eye barrier, and/or the blood-nerve barrier and therefore be of improved diagnostic and/or therapeutic use in humans and other mammals. These methods involve perispinal administration of imaging agents without direct intrathecal injection. Perispinal administration is defined as administration of the molecule into the anatomic area within 10 cm of the spine. Perispinal administration results in absorption of the imaging agent into the vertebral venous system. The vertebral venous system is capable of transporting molecules into the brain, the eye, the retina, the auditory apparatus, the cranial nerves, the head, the spine, the spinal cord, the vertebral bodies, the dorsal root ganglia, and the nerve roots via retrograde venous flow, thereby bypassing the blood-brain barrier and similar barriers and delivering the molecules to the brain, the eye, the retina, the auditory apparatus, the cranial nerves, the head, the spine (including the vertebral bodies), the spinal cord, the dorsal root ganglia, or the nerve roots. This method may be utilized for a wide variety of diagnostic agents, including, but not limited to biologics, monoclonal antibodies, fusion proteins, monoclonal antibody fragments, antibodies to tumor antigens, hormones, cytokines, anti-cytokines, interleukins, anti-interleukins, interferons, colony-stimulating factors, cancer chemotherapeutic agents, growth factors, anti-virals and antibiotics, including those which are radiolabeled, iodinated, or otherwise altered to facilitate diagnostic imaging. Included in these novel methods are perispinal delivery of amyloid imaging agents, and other ligands radiolabeled with [11C] or [18F] to faciliate PET imaging of the brain.